SIRT1
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Also known as SIR2L1
Summary
SIRT1 (sirtuin 1, HGNC:14929) is a protein-coding gene on chromosome 10q21.3, encoding NAD-dependent protein deacetylase sirtuin-1 (Q96EB6). NAD-dependent protein deacetylase that links transcriptional regulation directly to intracellular energetics and participates in the coordination of several separated cellular functions such as cell cycle, response to DNA damage, metabolism, apoptosis and autophagy. In precision oncology, SIRT1 Overexpression is associated with resistance to Niacinamide in Pancreatic Cancer (CIViC Level D).
This gene encodes a member of the sirtuin family of proteins, homologs to the yeast Sir2 protein. Members of the sirtuin family are characterized by a sirtuin core domain and grouped into four classes. The functions of human sirtuins have not yet been determined; however, yeast sirtuin proteins are known to regulate epigenetic gene silencing and suppress recombination of rDNA. Studies suggest that the human sirtuins may function as intracellular regulatory proteins with mono-ADP-ribosyltransferase activity. The protein encoded by this gene is included in class I of the sirtuin family. Alternative splicing results in multiple transcript variants.
Source: NCBI Gene 23411 — RefSeq curated summary.
At a glance
- Gene–disease (curated): monogenic diabetes (Limited, ClinGen) — +1 more curated relationship
- GWAS associations: 5
- Clinical variants (ClinVar): 149 total
- Druggable target: yes — 6 molecules with ChEMBL bioactivity
- Precision-oncology evidence (CIViC): 1 curated variant–drug association
- Transcription factor: yes — 63 downstream targets (CollecTRI)
- MANE Select transcript:
NM_012238
Identifiers
Gene identifiers
| Field | Value |
|---|---|
| HGNC ID | HGNC:14929 |
| Approved symbol | SIRT1 |
| Name | sirtuin 1 |
| Location | 10q21.3 |
| Locus type | gene with protein product |
| Status | Approved |
| Aliases | SIR2L1 |
| Ensembl gene | ENSG00000096717 |
| Ensembl biotype | protein_coding |
| OMIM | 604479 |
| Entrez | 23411 |
Gene structure
Transcript identifiers
Ensembl transcripts: 13 — 11 protein_coding, 2 protein_coding_CDS_not_defined
ENST00000212015, ENST00000403579, ENST00000406900, ENST00000432464, ENST00000473922, ENST00000497639, ENST00000872482, ENST00000923647, ENST00000923648, ENST00000923649, ENST00000923650, ENST00000959939, ENST00000959940
RefSeq mRNA: 3 — MANE Select: NM_012238
NM_001142498, NM_001314049, NM_012238
CCDS: CCDS44412, CCDS7273, CCDS81469
Canonical transcript exons
ENST00000212015 — 9 exons
| Exon | Start | End |
|---|---|---|
| ENSE00000706429 | 67906790 | 67906937 |
| ENSE00000706432 | 67908046 | 67908125 |
| ENSE00000706435 | 67909256 | 67909442 |
| ENSE00000706437 | 67912474 | 67913031 |
| ENSE00000834120 | 67884656 | 67885151 |
| ENSE00001562862 | 67916265 | 67918390 |
| ENSE00003475599 | 67888882 | 67889123 |
| ENSE00003522189 | 67887417 | 67887533 |
| ENSE00003593793 | 67891402 | 67891554 |
Expression profiles
Bgee: expression breadth ubiquitous, 280 present calls, max score 91.25.
FANTOM5 (CAGE): breadth ubiquitous, TPM avg 23.2513 / max 580.1176, expressed in 1812 samples.
FANTOM5 promoters (2 alternative TSS)
| Promoter ID | TPM avg | Samples expressed |
|---|---|---|
| 105207 | 15.6629 | 1785 |
| 105208 | 7.5884 | 1688 |
Top tissues by expression
291 total, by Bgee expression score (0-100, higher = more expressed):
| Tissue | Anatomy ID | Expression score | Quality |
|---|---|---|---|
| calcaneal tendon | UBERON:0003701 | 91.25 | gold quality |
| ganglionic eminence | UBERON:0004023 | 90.50 | gold quality |
| ventricular zone | UBERON:0003053 | 89.75 | gold quality |
| cortical plate | UBERON:0005343 | 89.46 | gold quality |
| adrenal tissue | UBERON:0018303 | 89.29 | gold quality |
| primordial germ cell in gonad | CL:0000670 ∩ UBERON:0000991 | 88.84 | gold quality |
| male germ line stem cell (sensu Vertebrata) in testis | CL:0000089 ∩ UBERON:0000473 | 88.31 | gold quality |
| blood vessel layer | UBERON:0004797 | 88.04 | gold quality |
| mucosa of stomach | UBERON:0001199 | 87.56 | gold quality |
| right adrenal gland cortex | UBERON:0035827 | 87.43 | gold quality |
| left adrenal gland cortex | UBERON:0035825 | 87.35 | gold quality |
| adrenal gland | UBERON:0002369 | 87.18 | gold quality |
| left adrenal gland | UBERON:0001234 | 86.99 | gold quality |
| right adrenal gland | UBERON:0001233 | 86.77 | gold quality |
| adrenal cortex | UBERON:0001235 | 86.72 | gold quality |
| leukocyte | CL:0000738 | 86.50 | gold quality |
| monocyte | CL:0000576 | 86.47 | gold quality |
| tibial artery | UBERON:0007610 | 86.45 | gold quality |
| popliteal artery | UBERON:0002250 | 86.44 | gold quality |
| mononuclear cell | CL:0000842 | 86.39 | gold quality |
| epithelium of nasopharynx | UBERON:0001951 | 86.21 | gold quality |
| skin of hip | UBERON:0001554 | 86.20 | gold quality |
| lower lobe of lung | UBERON:0008949 | 85.99 | gold quality |
| artery | UBERON:0001637 | 85.92 | gold quality |
| right testis | UBERON:0004534 | 85.92 | gold quality |
| left testis | UBERON:0004533 | 85.80 | gold quality |
| testis | UBERON:0000473 | 85.74 | gold quality |
| left ovary | UBERON:0002119 | 85.73 | gold quality |
| gall bladder | UBERON:0002110 | 85.55 | gold quality |
| hindlimb stylopod muscle | UBERON:0004252 | 85.52 | gold quality |
Single-cell (SCXA)
Detected in 2 experiment(s), a significant marker in 2.
| Experiment | Marker? | Max mean expression |
|---|---|---|
| E-GEOD-100618 | yes | 344.14 |
| E-ANND-3 | yes | 10.42 |
Regulation
Is transcription factor: yes
Downstream targets (CollecTRI)
63 targets.
| Target | Regulation |
|---|---|
| ABCB1 | Activation |
| ACAN | Activation |
| ADAMTS5 | Repression |
| BCL11A | Repression |
| CCAR2 | Repression |
| CCND1 | Repression |
| CDH1 | Repression |
| CDKN1A | Repression |
| CFH | Repression |
| CFLAR | Activation |
| COL10A1 | Repression |
| COL1A2 | Repression |
| CTNNB1 | Repression |
| CYP7A1 | Activation |
| DLL4 | Repression |
| EGLN1 | Repression |
| ESRRG | Activation |
| EZH2 | Repression |
| FOXO3 | Repression |
| FOXP3 | Unknown |
| GADD45G | |
| GLI1 | |
| HBE1 | Repression |
| HES5 | |
| HIC1 | Unknown |
| HIF1A | Activation |
| HSF1 | Activation |
| HSPA4 | Unknown |
| HYOU1 | Activation |
| ICAM1 | Repression |
Upstream regulators (CollecTRI, top): ATF4, BATF, BCL11A, BCL11B, BCL6, BCLAF1, BMAL1, BRCA1, CEBPA, CEBPB, CEBPG, CIITA, CLOCK, DDIT3, E2F1, ELF1, ESR1, FOXC1, FOXD4, FOXL2, FOXO1, FOXO3, FOXO4, GATA4, GTF2I, HES1, HIC1, JUN, MECP2, MYC, NCOA1, NCOR1, NEUROG2, NFKB, NKX2-5, NR0B2, NR1H3, NR2E1, NR3C1, NR4A2
miRNA regulators (miRDB)
160 targeting SIRT1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):
| miRNA | Max score | Avg score | miRNA target_count |
|---|---|---|---|
| HSA-MIR-5692A | 100.00 | 74.40 | 6850 |
| HSA-MIR-9-5P | 100.00 | 72.28 | 2361 |
| HSA-MIR-3613-3P | 100.00 | 76.36 | 7965 |
| HSA-MIR-190A-3P | 100.00 | 80.35 | 5520 |
| HSA-MIR-29A-3P | 100.00 | 73.11 | 1835 |
| HSA-MIR-29B-3P | 100.00 | 73.18 | 1833 |
| HSA-MIR-29C-3P | 100.00 | 73.15 | 1833 |
| HSA-MIR-4262 | 100.00 | 73.26 | 3931 |
| HSA-MIR-30A-5P | 100.00 | 76.31 | 3233 |
| HSA-MIR-30B-5P | 100.00 | 76.29 | 3248 |
| HSA-MIR-30C-5P | 100.00 | 76.29 | 3248 |
| HSA-MIR-30D-5P | 100.00 | 76.32 | 3233 |
| HSA-MIR-30E-5P | 100.00 | 76.32 | 3242 |
| HSA-MIR-200B-3P | 100.00 | 73.31 | 2693 |
| HSA-MIR-200C-3P | 100.00 | 73.35 | 2685 |
| HSA-MIR-429 | 100.00 | 73.44 | 2698 |
| HSA-MIR-1252-5P | 100.00 | 69.80 | 2774 |
| HSA-MIR-548C-3P | 99.99 | 74.01 | 7587 |
| HSA-MIR-186-5P | 99.99 | 70.83 | 3707 |
| HSA-MIR-513B-5P | 99.99 | 69.96 | 2150 |
| HSA-MIR-181A-5P | 99.99 | 72.96 | 2995 |
| HSA-MIR-181B-5P | 99.99 | 72.97 | 2996 |
| HSA-MIR-181C-5P | 99.99 | 72.95 | 2996 |
| HSA-MIR-181D-5P | 99.99 | 73.04 | 2997 |
| HSA-MIR-4789-3P | 99.99 | 70.75 | 2484 |
| HSA-MIR-34A-5P | 99.99 | 71.21 | 1784 |
| HSA-MIR-449A | 99.99 | 71.05 | 1776 |
| HSA-MIR-12136 | 99.98 | 72.81 | 5713 |
| HSA-MIR-520D-5P | 99.98 | 73.34 | 4883 |
| HSA-MIR-524-5P | 99.98 | 73.43 | 4882 |
Literature-anchored findings (GeneRIF, showing 40)
- SIRT1(Sir2alpha) deacetylates p53 and promotes survival (PMID:11672522)
- the SIRT1 deacetylase as a novel negative regulator of p53 function capable of modulating cellular senescence (PMID:12006491)
- Data show that physiological concentrations of nicotinamide noncompetitively inhibit SIRT1 in vitro. (PMID:12297502)
- These results indicate that the molecular association between HES1-, HEY2- and SIRT1-related proteins is conserved among metazoans, from Drosophila to human, and suggest that the Sir2-bHLH interaction also plays important roles in human cells. (PMID:12535671)
- SIRT1 is a histone H3/H4 deacetylase in mammalian cells and in transcriptional repression mediated by CTIP2 (PMID:12930829)
- SIRT1 and FOXO3 formed a complex in cells in response to oxidative stress; SIRT1 deacetylated FOXO3; SIRT1 increased FOXO3’s ability to induce cell cycle arrest and resistance to oxidative stress but inhibited FOXO3’s ability to induce cell death (PMID:14976264)
- SIRT1 represses forkhead transcription factors and reduces apoptosis (PMID:14980222)
- Data demonstrate that acetylation functions in a second pathway of negative control for FOXO factors and provides a novel mechanism whereby hSir2(SIRT1) can promote cellular survival and increase lifespan. (PMID:15126506)
- provides evidence that SIRT1 activity augments apoptosis in response to TNFalpha by the ability of the deacetylase to inhibit the transactivation potential of the RelA/p65 protein (PMID:15152190)
- SIRT1 deacetylates the DNA repair factor Ku70, causing it to sequester the proapoptotic factor Bax away from mitochondria, thereby inhibiting stress-induced apoptotic cell death (PMID:15205477)
- SIRT1 deacetylation and repression of p300 involves specific lysine residues in the cell cycle regulatory domain 1 (PMID:15632193)
- SIRT1 has a role in transcriptional repression mediated by BCL11A in mammalian cells (PMID:15639232)
- substrate recognition by SIRT1 does not depend on the amino acid sequence proximate to the acetylated lysine (PMID:15640142)
- FHL2 inhibits FOXO1 activity in prostate cancer cells by promoting the deacetylation of FOXO1 by SIRT1 (PMID:15692560)
- Hiv Tat is deacetylated by human sirtuin 1 (SIRT1), a nicotinamide adenine dinucleotide-dependent class III protein deacetylase in vitro and in vivo (PMID:15719057)
- binding of resveratrol to SIRT1 promotes a conformational change that accommodates the attached coumarin group (PMID:15749705)
- histone deacetylase 4- and SIRT1 deacetylase-mediated lysine modifications regulate MEF2 (PMID:16166628)
- SIRT1 protects against microglia-dependent amyloid-beta toxicity through inhibiting NF-kappaB signaling (PMID:16183991)
- PARP activation and the concomitant reduction of Sir2alpha activity in failing hearts regulate the post-translational acetylation of p53 (PMID:16207712)
- Overexpression of sirt1 induced expression of P-glycoprotein and rendered cancer cells resistant to doxorubicin. (PMID:16288004)
- Data describe the cloning, chromosomal characterization and mapping of the NAD-dependent histone deacetylases gene sirtuin 1.( (PMID:16328012)
- Although SIRT1 deacetylates p53, this does not play a role in cell survival following DNA damage in certain cell lines and primary human mammary epithelial cells. (PMID:16354677)
- AIF-mediated cell death is regulated by the functional interplay of SIRT1 and PARP-1 in response to DNA damage (PMID:16628003)
- expression of SIRT1 in the brain resulted in decreased ROCK1 expression and elevated alpha-secretase activity; SIRT1 activation in the brain is a novel mechanism through which calorie restriction may influence Alzheimer disease amyloid neuropathology (PMID:16751189)
- There is a mutual regulation between E2F1 and SirT1 that affects cellular sensitivity to DNA damage. (PMID:16892051)
- evidence for an androgen receptor (AR) regulatory pathway controlled by SIRT1; SIRT1 antagonists induce endogenous AR expression and enhance dihydrotestosterone-mediated AR expression (PMID:16923962)
- SIRT1 can modulate p73 activity via deacetylation. (PMID:16998810)
- SIRT1 regulates cigarette smoke induced pro-inflammatory mediators release via RelA/p65 NF-{kappa}B in macrophages. (PMID:17041012)
- These data show that SIRT1 regulates cigarette smoke-mediated proinflammatory mediator release via NF-kappaB, implicating a role of SIRT1 in sustained inflammation and aging of the lungs. (PMID:17041012)
- In contrast, a SIRT1 inhibitory compound showed a stimulatory activity on the differentiation of adipocytes, a feature often linked to insulin sensitization. (PMID:17099246)
- The association of three Sirt1 SNPs and energy homeostasis in Finnish subjects implicates SIRT1 as a key regulator of energy and metabolic homeostasis. (PMID:17112576)
- Overexpression of SIRT1 may have some relevance to the early stage of skin carcinogenesis. (PMID:17180656)
- HIC1 is a target of the class III deacetylase SIRT1 and identify a new posttranslational modification step in the P53-HIC1-SIRT1 regulatory loop. (PMID:17283066)
- HuR regulates SIRT1 expression, underscore functional links between the two stress-response proteins, and implicate Chk2 in these processes. (PMID:17317627)
- SIRT1 modulates DNA repair activity, which could be regulated by the acetylation status of repair protein Ku70 following DNA damage (PMID:17334224)
- Corepressor of androgen receptor, elucidating a new pathway relevant to prostate cancer growth and approaches to therapy. (PMID:17505061)
- SIRT1 was distributed in cytoplasm at metaphase during mitosis, and overexpression of SIRT1 significantly augmented apoptosis for cells at metaphase. (PMID:17516504)
- SIRT1 constitutes a unique molecular link between aging and human neurodegenerative disorders and provides a promising avenue for therapeutic intervention (PMID:17581637)
- Deacetylation of NBS1 by SIRT1 plays a key role in the dynamic regulation of the DNA damage response and in the maintenance of genomic stability. (PMID:17612497)
- downregulation of Sirt1 decreases survival and increases radiation-induced antiproliferation effects of human lung cancer cells (PMID:17624472)
Cross-species orthologs
5 orthologs
| Organism | Symbol | Gene ID |
|---|---|---|
| danio_rerio | sirt1 | ENSDARG00000068064 |
| mus_musculus | Sirt1 | ENSMUSG00000020063 |
| rattus_norvegicus | Sirt1 | ENSRNOG00000051592 |
| drosophila_melanogaster | Sirt1 | FBGN0024291 |
| caenorhabditis_elegans | WBGENE00004800 |
Paralogs (6): SIRT2 (ENSG00000068903), SIRT6 (ENSG00000077463), SIRT4 (ENSG00000089163), SIRT5 (ENSG00000124523), SIRT3 (ENSG00000142082), SIRT7 (ENSG00000187531)
Protein
Protein identifiers
NAD-dependent protein deacetylase sirtuin-1 — Q96EB6 (reviewed: Q96EB6)
Alternative names: NAD-dependent protein deacylase sirtuin-1, Regulatory protein SIR2 homolog 1, SIR2-like protein 1
All UniProt accessions (3): Q96EB6, B0QZ35, E9PC49
UniProt curated annotations — full annotation on UniProt →
Function. NAD-dependent protein deacetylase that links transcriptional regulation directly to intracellular energetics and participates in the coordination of several separated cellular functions such as cell cycle, response to DNA damage, metabolism, apoptosis and autophagy. Can modulate chromatin function through deacetylation of histones and can promote alterations in the methylation of histones and DNA, leading to transcriptional repression. Deacetylates a broad range of transcription factors and coregulators, thereby regulating target gene expression positively and negatively. Serves as a sensor of the cytosolic ratio of NAD(+)/NADH which is altered by glucose deprivation and metabolic changes associated with caloric restriction. Is essential in skeletal muscle cell differentiation and in response to low nutrients mediates the inhibitory effect on skeletal myoblast differentiation which also involves 5’-AMP-activated protein kinase (AMPK) and nicotinamide phosphoribosyltransferase (NAMPT). Component of the eNoSC (energy-dependent nucleolar silencing) complex, a complex that mediates silencing of rDNA in response to intracellular energy status and acts by recruiting histone-modifying enzymes. The eNoSC complex is able to sense the energy status of cell: upon glucose starvation, elevation of NAD(+)/NADP(+) ratio activates SIRT1, leading to histone H3 deacetylation followed by dimethylation of H3 at ‘Lys-9’ (H3K9me2) by SUV39H1 and the formation of silent chromatin in the rDNA locus. Deacetylates ‘Lys-266’ of SUV39H1, leading to its activation. Inhibits skeletal muscle differentiation by deacetylating PCAF and MYOD1. Deacetylates H2A and ‘Lys-26’ of H1-4. Deacetylates ‘Lys-16’ of histone H4 (in vitro). Involved in NR0B2/SHP corepression function through chromatin remodeling: Recruited to LRH1 target gene promoters by NR0B2/SHP thereby stimulating histone H3 and H4 deacetylation leading to transcriptional repression. Proposed to contribute to genomic integrity via positive regulation of telomere length; however, reports on localization to pericentromeric heterochromatin are conflicting. Proposed to play a role in constitutive heterochromatin (CH) formation and/or maintenance through regulation of the available pool of nuclear SUV39H1. Upon oxidative/metabolic stress decreases SUV39H1 degradation by inhibiting SUV39H1 polyubiquitination by MDM2. This increase in SUV39H1 levels enhances SUV39H1 turnover in CH, which in turn seems to accelerate renewal of the heterochromatin which correlates with greater genomic integrity during stress response. Deacetylates ‘Lys-382’ of p53/TP53 and impairs its ability to induce transcription-dependent proapoptotic program and modulate cell senescence. Deacetylates TAF1B and thereby represses rDNA transcription by the RNA polymerase I. Deacetylates MYC, promotes the association of MYC with MAX and decreases MYC stability leading to compromised transformational capability. Deacetylates FOXO3 in response to oxidative stress thereby increasing its ability to induce cell cycle arrest and resistance to oxidative stress but inhibiting FOXO3-mediated induction of apoptosis transcriptional activity; also leading to FOXO3 ubiquitination and protesomal degradation. Appears to have a similar effect on MLLT7/FOXO4 in regulation of transcriptional activity and apoptosis. Deacetylates DNMT1; thereby impairs DNMT1 methyltransferase-independent transcription repressor activity, modulates DNMT1 cell cycle regulatory function and DNMT1-mediated gene silencing. Deacetylates RELA/NF-kappa-B p65 thereby inhibiting its transactivating potential and augments apoptosis in response to TNF. Deacetylates HIF1A, KAT5/TIP60, RB1 and HIC1. Deacetylates FOXO1 resulting in its nuclear retention and enhancement of its transcriptional activity leading to increased gluconeogenesis in liver. Inhibits E2F1 transcriptional activity and apoptotic function, possibly by deacetylation. Involved in HES1- and HEY2-mediated transcriptional repression. In cooperation with MYCN seems to be involved in transcriptional repression of DUSP6/MAPK3 leading to MYCN stabilization by phosphorylation at ‘Ser-62’. Deacetylates MEF2D. Required for antagonist-mediated transcription suppression of AR-dependent genes which may be linked to local deacetylation of histone H3. Represses HNF1A-mediated transcription. Required for the repression of ESRRG by CREBZF. Deacetylates NR1H3 and NR1H2 and deacetylation of NR1H3 at ‘Lys-434’ positively regulates transcription of NR1H3:RXR target genes, promotes NR1H3 proteasomal degradation and results in cholesterol efflux; a promoter clearing mechanism after reach round of transcription is proposed. Involved in lipid metabolism: deacetylates LPIN1, thereby inhibiting diacylglycerol synthesis. Implicated in regulation of adipogenesis and fat mobilization in white adipocytes by repression of PPARG which probably involves association with NCOR1 and SMRT/NCOR2. Deacetylates p300/EP300 and PRMT1. Deacetylates ACSS2 leading to its activation, and HMGCS1 deacetylation. Involved in liver and muscle metabolism. Through deacetylation and activation of PPARGC1A is required to activate fatty acid oxidation in skeletal muscle under low-glucose conditions and is involved in glucose homeostasis. Involved in regulation of PPARA and fatty acid beta-oxidation in liver. Involved in positive regulation of insulin secretion in pancreatic beta cells in response to glucose; the function seems to imply transcriptional repression of UCP2. Proposed to deacetylate IRS2 thereby facilitating its insulin-induced tyrosine phosphorylation. Deacetylates SREBF1 isoform SREBP-1C thereby decreasing its stability and transactivation in lipogenic gene expression. Involved in DNA damage response by repressing genes which are involved in DNA repair, such as XPC and TP73, deacetylating XRCC6/Ku70, and facilitating recruitment of additional factors to sites of damaged DNA, such as SIRT1-deacetylated NBN can recruit ATM to initiate DNA repair and SIRT1-deacetylated XPA interacts with RPA2. Also involved in DNA repair of DNA double-strand breaks by homologous recombination and specifically single-strand annealing independently of XRCC6/Ku70 and NBN. Promotes DNA double-strand breaks by mediating deacetylation of SIRT6. Transcriptional suppression of XPC probably involves an E2F4:RBL2 suppressor complex and protein kinase B (AKT) signaling. Transcriptional suppression of TP73 probably involves E2F4 and PCAF. Deacetylates WRN thereby regulating its helicase and exonuclease activities and regulates WRN nuclear translocation in response to DNA damage. Deacetylates APEX1 at ‘Lys-6’ and ‘Lys-7’ and stimulates cellular AP endonuclease activity by promoting the association of APEX1 to XRCC1. Catalyzes deacetylation of ERCC4/XPF, thereby impairing interaction with ERCC1 and nucleotide excision repair (NER). Increases p53/TP53-mediated transcription-independent apoptosis by blocking nuclear translocation of cytoplasmic p53/TP53 and probably redirecting it to mitochondria. Deacetylates XRCC6/Ku70 at ‘Lys-539’ and ‘Lys-542’ causing it to sequester BAX away from mitochondria thereby inhibiting stress-induced apoptosis. Is involved in autophagy, presumably by deacetylating ATG5, ATG7 and MAP1LC3B/ATG8. Deacetylates AKT1 which leads to enhanced binding of AKT1 and PDK1 to PIP3 and promotes their activation. Proposed to play role in regulation of STK11/LBK1-dependent AMPK signaling pathways implicated in cellular senescence which seems to involve the regulation of the acetylation status of STK11/LBK1. Can deacetylate STK11/LBK1 and thereby increase its activity, cytoplasmic localization and association with STRAD; however, the relevance of such activity in normal cells is unclear. In endothelial cells is shown to inhibit STK11/LBK1 activity and to promote its degradation. Deacetylates SMAD7 at ‘Lys-64’ and ‘Lys-70’ thereby promoting its degradation. Deacetylates CIITA and augments its MHC class II transactivation and contributes to its stability. Deacetylates MECOM/EVI1. Deacetylates PML at ‘Lys-487’ and this deacetylation promotes PML control of PER2 nuclear localization. During the neurogenic transition, represses selective NOTCH1-target genes through histone deacetylation in a BCL6-dependent manner and leading to neuronal differentiation. Regulates the circadian expression of several core clock genes, including BMAL1, RORC, PER2 and CRY1 and plays a critical role in maintaining a controlled rhythmicity in histone acetylation, thereby contributing to circadian chromatin remodeling. Deacetylates BMAL1 and histones at the circadian gene promoters in order to facilitate repression by inhibitory components of the circadian oscillator. Deacetylates PER2, facilitating its ubiquitination and degradation by the proteasome. Protects cardiomyocytes against palmitate-induced apoptosis. Deacetylates XBP1 isoform 2; deacetylation decreases protein stability of XBP1 isoform 2 and inhibits its transcriptional activity. Deacetylates PCK1 and directs its activity toward phosphoenolpyruvate production promoting gluconeogenesis. Involved in the CCAR2-mediated regulation of PCK1 and NR1D1. Deacetylates CTNB1 at ‘Lys-49’. In POMC (pro-opiomelanocortin) neurons, required for leptin-induced activation of PI3K signaling. Deacetylates SOX9; promoting SOX9 nuclear localization and transactivation activity. Involved in the regulation of centrosome duplication: deacetylates CENATAC in G1 phase, allowing for SASS6 accumulation on the centrosome and subsequent procentriole assembly. Deacetylates NDC80/HEC1. In addition to protein deacetylase activity, also acts as a protein-lysine deacylase by mediating protein delactylation, depropionylation and decrotonylation. Mediates depropionylation of Osterix (SP7). Catalyzes decrotonylation of histones; it however does not represent a major histone decrotonylase. Mediates protein delactylation of TEAD1 and YAP1. Deacetylates ‘Lys-382’ of p53/TP53, however with lower activity than isoform 1. In combination, the two isoforms exert an additive effect. Isoform 2 regulates p53/TP53 expression and cellular stress response and is in turn repressed by p53/TP53 presenting a SIRT1 isoform-dependent auto-regulatory loop. Catalytically inactive 75SirT1 may be involved in regulation of apoptosis. May be involved in protecting chondrocytes from apoptotic death by associating with cytochrome C and interfering with apoptosome assembly. (Microbial infection) In case of HIV-1 infection, interacts with and deacetylates the viral Tat protein. The viral Tat protein inhibits SIRT1 deacetylation activity toward RELA/NF-kappa-B p65, thereby potentiates its transcriptional activity and SIRT1 is proposed to contribute to T-cell hyperactivation during infection.
Subunit / interactions. Interacts with XBP1 isoform 2. Found in a complex with PCAF and MYOD1. Interacts with FOXO1; the interaction deacetylates FOXO1, resulting in its nuclear retention and promotion of its transcriptional activity Component of the eNoSC complex, composed of SIRT1, SUV39H1 and RRP8. Interacts with HES1, HEY2 and PML. Interacts with RPS19BP1/AROS. Interacts with CCAR2 (via N-terminus); the interaction disrupts the interaction between SIRT1 and p53/TP53. Interacts with SETD7; the interaction induces the dissociation of SIRT1 from p53/TP53 and increases p53/TP53 activity. Interacts with MYCN, NR1I2, CREBZF, TSC2, TLE1, FOS, JUN, NR0B2, PPARG, NCOR, IRS1, IRS2 and NMNAT1. Interacts with HNF1A; the interaction occurs under nutrient restriction. Interacts with SUZ12; the interaction mediates the association with the PRC4 histone methylation complex which is specific as an association with PCR2 and PCR3 complex variants is not found. Interacts with BCL6; leads to a epigenetic repression of specific target genes. Interacts with CLOCK, BMAL1 and PER2. Interacts with PPARA; the interaction seems to be modulated by NAD(+) levels. Interacts with NR1H3 and this interaction is inhibited in the presence of CCAR2. Interacts with CHEK2. Interacts with p53/TP53. Exhibits a preferential interaction with sumoylated CCAR2 over its unmodified form. Interacts with PACS2. Interacts with SIRT7. Interacts with PUS7. Interacts with TULP3. Interacts with MORN3; the interaction enhances the ubiquitination of p53/TP53. Interacts with NAP1L2; to promote deacetylation of histone H3 on ‘Lys-14’. (Microbial infection) Interacts with HIV-1 Tat.
Subcellular location. Nucleus. PML body. Cytoplasm. Nucleus Cytoplasm. Mitochondrion.
Tissue specificity. Widely expressed.
Post-translational modifications. Methylated on multiple lysine residues; methylation is enhanced after DNA damage and is dispensable for deacetylase activity toward p53/TP53. Phosphorylated. Phosphorylated by STK4/MST1, resulting in inhibition of SIRT1-mediated p53/TP53 deacetylation. Phosphorylation by MAPK8/JNK1 at Ser-27, Ser-47, and Thr-530 leads to increased nuclear localization and enzymatic activity. Phosphorylation at Thr-530 by DYRK1A and DYRK3 activates deacetylase activity and promotes cell survival. Phosphorylation by mammalian target of rapamycin complex 1 (mTORC1) at Ser-47 inhibits deacetylation activity. Phosphorylated by CaMK2, leading to increased p53/TP53 and NF-kappa-B p65/RELA deacetylation activity. Phosphorylation at Ser-27 implicating MAPK9 is linked to protein stability. There is some ambiguity for some phosphosites: Ser-159/Ser-162 and Thr-544/Ser-545. Proteolytically cleaved by cathepsin B upon TNF treatment to yield catalytic inactive but stable SirtT1 75 kDa fragment (75SirT1). S-nitrosylated by GAPDH, leading to inhibit the NAD-dependent protein deacetylase activity. Acetylated at various Lys residues. Deacetylated via an autocatalytic mechanism. Autodeacetylation at Lys-238 promotes its protein deacetylase activity. Ubiquitinated; leading to degradation. Deubiquitinated by USP22; leading to stabilization.
Activity regulation. Inhibited by nicotinamide. Activated by resveratrol (3,5,4’-trihydroxy-trans-stilbene), butein (3,4,2’,4’-tetrahydroxychalcone), piceatannol (3,5,3’,4’-tetrahydroxy-trans-stilbene), Isoliquiritigenin (4,2’,4’-trihydroxychalcone), fisetin (3,7,3’,4’-tetrahydroxyflavone) and quercetin (3,5,7,3’,4’-pentahydroxyflavone). MAPK8/JNK1 and RPS19BP1/AROS act as positive regulators of deacetylation activity. Negatively regulated by CCAR2.
Cofactor. Binds 1 zinc ion per subunit.
Induction. Up-regulated by methyl methanesulfonate (MMS). In H293T cells by presence of rat calorie restriction (CR) serum.
Miscellaneous. Red wine, which contains resveratrol, may participate in activation of sirtuin proteins, and may therefore participate in an extended lifespan as it has been observed in yeast. Calf histone H1 is used as substrate in the in vitro deacetylation assay. As, in vivo, interaction occurs between SIRT1 with H1-4, deacetylation has been validated only for H1-4. The reported ADP-ribosyltransferase activity of sirtuins is likely some inefficient side reaction of the deacetylase activity and may not be physiologically relevant.
Similarity. Belongs to the sirtuin family. Class I subfamily.
Isoforms (2)
| UniProt ID | Names | Canonical? |
|---|---|---|
| Q96EB6-1 | 1 | yes |
| Q96EB6-2 | 2, delta-exon8 |
RefSeq proteins (3): NP_001135970, NP_001300978, NP_036370* (*=MANE)
Domains & families (InterPro)
| ID | Name | Type |
|---|---|---|
| IPR003000 | Sirtuin | Family |
| IPR026590 | Ssirtuin_cat_dom | Domain |
| IPR026591 | Sirtuin_cat_small_dom_sf | Homologous_superfamily |
| IPR029035 | DHS-like_NAD/FAD-binding_dom | Homologous_superfamily |
| IPR050134 | NAD-dep_sirtuin_deacylases | Family |
Pfam: PF02146
Enzyme classification (BRENDA):
- EC 2.3.1.286 — protein acetyllysine N-acetyltransferase (BRENDA: 13 organisms, 147 substrates, 140 inhibitors, 18 Km, 11 kcat entries)
Substrate kinetics (BRENDA)
11 substrates with measured Km, best-characterized 11. Km ranges are aggregated across organisms/conditions.
| Substrate | Km (mM) | Measurements |
|---|---|---|
| NAD+ | 0.0161–0.4535 | 4 |
| NICOTINAMIDE | 0.037–0.16 | 3 |
| [HISTONE H3]-N6-ACETYL-L-LYSINE9 | 0.019–0.039 | 2 |
| [HISTONE H3]-N6-MYRISTOYL-L-LYSINE9 | 0.0002–0.001 | 2 |
| K382AZAKAC-CONTAINING P53 PEPTIDE | 0.0109 | 1 |
| K382KAC-CONTAINING P53 PEPTIDE | 0.0718 | 1 |
| [HISTONE H3]-N6-ACETYL-L-LYSINE | 0.372 | 1 |
| [HISTONE H3]-N6-BUTYRYL-L-LYSINE9 | 0.008 | 1 |
| [HISTONE H3]-N6-OCTANOYL-L-LYSINE9 | 0.0012 | 1 |
| [HISTONE H4]-N6-ACETYL-L-LYSINE | 0.176 | 1 |
| [PEPTIDE P300]-N6-ACETYL-L-LYSINE | 0.085 | 1 |
Catalyzed reactions (Rhea), 4 shown:
- N(6)-propanoyl-L-lysyl-[protein] + NAD(+) + H2O = 3’’-O-propanoyl-ADP-D-ribose + nicotinamide + L-lysyl-[protein] (RHEA:23500)
- N(6)-acetyl-L-lysyl-[protein] + NAD(+) + H2O = 2’’-O-acetyl-ADP-D-ribose + nicotinamide + L-lysyl-[protein] (RHEA:43636)
- N(6)-(2E)-butenoyl-L-lysyl-[protein] + NAD(+) + H2O = 2’’-O-(2E)-but-2-enoyl-ADP-D-ribose + nicotinamide + L-lysyl-[protein] (RHEA:69332)
- N(6)-[(S)-lactoyl]-L-lysyl-[protein] + NAD(+) + H2O = 2’’-O-(S)-lactoyl-ADP-D-ribose + nicotinamide + L-lysyl-[protein] (RHEA:80287)
UniProt features (118 total): modified residue 24, helix 20, strand 16, mutagenesis site 16, region of interest 9, binding site 9, compositionally biased region 6, turn 5, short sequence motif 4, chain 2, sequence variant 2, initiator methionine 1, active site 1, domain 1, splice variant 1, sequence conflict 1
Structure
Experimental structures (PDB)
9 structures.
| PDB | Method | Resolution (Å) |
|---|---|---|
| 8ANB | X-RAY DIFFRACTION | 1.64 |
| 4KXQ | X-RAY DIFFRACTION | 1.85 |
| 4IF6 | X-RAY DIFFRACTION | 2.25 |
| 4I5I | X-RAY DIFFRACTION | 2.5 |
| 4IG9 | X-RAY DIFFRACTION | 2.64 |
| 4ZZI | X-RAY DIFFRACTION | 2.73 |
| 4ZZJ | X-RAY DIFFRACTION | 2.74 |
| 4ZZH | X-RAY DIFFRACTION | 3.1 |
| 5BTR | X-RAY DIFFRACTION | 3.2 |
Predicted structure (AlphaFold)
| Model | pLDDT | Fraction very-high |
|---|---|---|
| AF-Q96EB6-F1 | 66.32 | 0.38 |
Functional residue map
Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.
Catalytic / active sites (1): 363 (proton acceptor)
Ligand- & substrate-binding residues (9): 261–280; 345–348; 371; 374; 395; 398; 440–442; 465–467; 482
Post-translational modifications (24): 2, 14, 26, 27, 47, 159, 162, 172, 173, 238, 377, 395, 398, 430, 513, 530, 535, 544, 545, 610 …
Mutagenesis-validated functional residues (16):
| Position | Phenotype |
|---|---|
| 27 | greatly diminishes phosphorylation by mapk8; when associated with a-47 and a-530. |
| 47 | blocks residue phosphorylation, restores deacetylation activity and inhibits dna damage-induced apoptosis. |
| 47 | greatly diminishes phosphorylation by mapk8; when associated with a-27 and a-530. |
| 233 | impairs in vitro methylation by setd7; when associated with r-235, r-236 and r-238. |
| 235 | impairs in vitro methylation by setd7; when associated with r-233, r-236 and r-238. |
| 236 | impairs in vitro methylation by setd7; when associated with r-233, r-235 and r-238. |
| 238 | impairs in vitro methylation by setd7; when associated with r-233, r-235a and r-236. |
| 256–257 | loss of interaction with the sumoylated form of ccar2. no effect on its deacetylation activity. |
| 363 | loss of function; abolishes both protein deacetylase, delactylase and decrotonylase activities. reduces the interaction |
| 474 | abolishes phosphorylation at ser-47, restores deacetylation activity and inhibits dna damage-induced apoptosis. |
| 530 | greatly diminishes phosphorylation by mapk8; when associated with a-27 and a-47. |
| 530 | reduces in vitro phosphorylation by cdk1. impairs cell proliferation and cell cycle progression; when associated with a- |
| 540 | reduces in vitro phosphorylation by cdk1. impairs cell proliferation and cell cycle progression; when associated with a- |
| 659 | reduces in vitro phosphorylation by camk2; when associated with s-661. greatly reduces in vivo phosphorylation; when ass |
| 661 | reduces in vitro phosphorylation by camk2; when associated with s-659. greatly reduces in vivo phosphorylation; when ass |
| 684 | no effect on phosphorylation (in vitro and in vivo). |
Function
Pathways and Gene Ontology
Reactome pathways
25 pathways
| ID | Pathway |
|---|---|
| R-HSA-3371453 | Regulation of HSF1-mediated heat shock response |
| R-HSA-427359 | SIRT1 negatively regulates rRNA expression |
| R-HSA-9617629 | Regulation of FOXO transcriptional activity by acetylation |
| R-HSA-9707616 | Heme signaling |
| R-HSA-9764725 | Negative Regulation of CDH1 Gene Transcription |
| R-HSA-9841922 | MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesis and hepatic steatosis |
| R-HSA-9854907 | Regulation of MITF-M dependent genes involved in metabolism |
| R-HSA-9856649 | Transcriptional and post-translational regulation of MITF-M expression and activity |
| R-HSA-9931509 | Expression of BMAL (ARNTL), CLOCK, and NPAS2 |
| R-HSA-1266738 | Developmental Biology |
| R-HSA-212165 | Epigenetic regulation of gene expression |
| R-HSA-212436 | Generic Transcription Pathway |
| R-HSA-2262752 | Cellular responses to stress |
| R-HSA-3371556 | Cellular response to heat stress |
| R-HSA-400253 | |
| R-HSA-5250941 | Negative epigenetic regulation of rRNA expression |
| R-HSA-73857 | RNA Polymerase II Transcription |
| R-HSA-74160 | Gene expression (Transcription) |
| R-HSA-8953897 | Cellular responses to stimuli |
| R-HSA-9614085 | FOXO-mediated transcription |
| R-HSA-9730414 | MITF-M-regulated melanocyte development |
| R-HSA-9818564 | Epigenetic regulation of gene expression by MLL3 and MLL4 complexes |
| R-HSA-9851695 | Epigenetic regulation of adipogenesis genes by MLL3 and MLL4 complexes |
| R-HSA-9856651 | MITF-M-dependent gene expression |
| R-HSA-9917777 | Epigenetic regulation by WDR5-containing histone modifying complexes |
MSigDB gene sets: 831 (showing top):
GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_CIRCADIAN_RHYTHM, GOBP_REGULATION_OF_DOUBLE_STRAND_BREAK_REPAIR, PID_HDAC_CLASSI_PATHWAY, GOBP_ACYLGLYCEROL_HOMEOSTASIS, GOBP_CHROMOSOME_ORGANIZATION, SHEPARD_BMYB_MORPHOLINO_UP, GOBP_ATTACHMENT_OF_SPINDLE_MICROTUBULES_TO_KINETOCHORE, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_NEGATIVE_REGULATION_OF_NEURON_APOPTOTIC_PROCESS, GOBP_REGULATION_OF_LIPID_STORAGE, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOBP_RESPONSE_TO_IONIZING_RADIATION, GOBP_INTRINSIC_APOPTOTIC_SIGNALING_PATHWAY_IN_RESPONSE_TO_DNA_DAMAGE_BY_P53_CLASS_MEDIATOR, GOBP_REGULATION_OF_AUTOPHAGY
GO Biological Process (125): single strand break repair (GO:0000012), negative regulation of transcription by RNA polymerase II (GO:0000122), rDNA heterochromatin formation (GO:0000183), pyrimidine dimer repair by nucleotide-excision repair (GO:0000720), DNA synthesis involved in DNA repair (GO:0000731), angiogenesis (GO:0001525), ovulation from ovarian follicle (GO:0001542), intracellular glucose homeostasis (GO:0001678), positive regulation of protein phosphorylation (GO:0001934), positive regulation of endothelial cell proliferation (GO:0001938), positive regulation of adaptive immune response (GO:0002821), chromatin organization (GO:0006325), DNA methylation-dependent constitutive heterochromatin formation (GO:0006346), protein deacetylation (GO:0006476), triglyceride mobilization (GO:0006642), DNA damage response (GO:0006974), response to oxidative stress (GO:0006979), transforming growth factor beta receptor signaling pathway (GO:0007179), spermatogenesis (GO:0007283), regulation of mitotic cell cycle (GO:0007346), muscle organ development (GO:0007517), positive regulation of cell population proliferation (GO:0008284), cellular response to starvation (GO:0009267), negative regulation of gene expression (GO:0010629), regulation of centrosome duplication (GO:0010824), negative regulation of triglyceride biosynthetic process (GO:0010868), positive regulation of cholesterol efflux (GO:0010875), regulation of lipid storage (GO:0010883), regulation of glucose metabolic process (GO:0010906), positive regulation of macroautophagy (GO:0016239), protein ubiquitination (GO:0016567), peptidyl-lysine acetylation (GO:0018394), macrophage differentiation (GO:0030225), negative regulation of transforming growth factor beta receptor signaling pathway (GO:0030512), endoplasmic reticulum unfolded protein response (GO:0030968), negative regulation of prostaglandin biosynthetic process (GO:0031393), heterochromatin formation (GO:0031507), subtelomeric heterochromatin formation (GO:0031509), protein destabilization (GO:0031648), negative regulation of TOR signaling (GO:0032007)
GO Molecular Function (37): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), p53 binding (GO:0002039), transcription coactivator activity (GO:0003713), transcription corepressor activity (GO:0003714), histone deacetylase activity (GO:0004407), enzyme inhibitor activity (GO:0004857), enzyme activator activity (GO:0008047), nuclear receptor binding (GO:0016922), histone deacetylase activity, NAD-dependent (GO:0017136), deacetylase activity (GO:0019213), enzyme binding (GO:0019899), histone H3K14 deacetylase activity, NAD-dependent (GO:0032041), protein lysine deacetylase activity (GO:0033558), NAD-dependent protein lysine deacetylase activity (GO:0034979), histone binding (GO:0042393), identical protein binding (GO:0042802), HLH domain binding (GO:0043398), bHLH transcription factor binding (GO:0043425), metal ion binding (GO:0046872), histone H3K9 deacetylase activity, NAD-dependent (GO:0046969), histone H4K16 deacetylase activity, NAD-dependent (GO:0046970), mitogen-activated protein kinase binding (GO:0051019), NAD+ binding (GO:0070403), NAD-dependent protein-lysine depropionylase activity (GO:0106231), DNA-binding transcription factor binding (GO:0140297), transcription regulator inhibitor activity (GO:0140416), histone H4K12 deacetylase activity, hydrolytic mechanism (GO:0140937), histone H3K deacetylase activity (GO:0141050), NAD-dependent protein lysine delactylase activity (GO:0141208), histone decrotonylase activity, NAD-dependent (GO:0160012), keratin filament binding (GO:1990254), promoter-specific chromatin binding (GO:1990841), protein binding (GO:0005515), transferase activity (GO:0016740), acyltransferase activity, transferring groups other than amino-acyl groups (GO:0016747), protein domain specific binding (GO:0019904), NAD-dependent protein decrotonylase activity (GO:0160011)
GO Cellular Component (19): chromosome, telomeric region (GO:0000781), chromatin (GO:0000785), euchromatin (GO:0000791), heterochromatin (GO:0000792), fibrillar center (GO:0001650), nucleus (GO:0005634), nuclear envelope (GO:0005635), nuclear inner membrane (GO:0005637), nucleoplasm (GO:0005654), chromatin silencing complex (GO:0005677), nucleolus (GO:0005730), cytoplasm (GO:0005737), mitochondrion (GO:0005739), cytosol (GO:0005829), PML body (GO:0016605), rDNA heterochromatin (GO:0033553), eNoSc complex (GO:0061773), protein-containing complex (GO:0032991), ESC/E(Z) complex (GO:0035098)
Reactome top-level categories
Rollup of top-14 pathways:
| Category | Pathways |
|---|---|
| Cellular responses to stress | 2 |
| Gene expression (Transcription) | 2 |
| Cellular response to heat stress | 1 |
| Negative epigenetic regulation of rRNA expression | 1 |
| FOXO-mediated transcription | 1 |
| Regulation of CDH1 Gene Transcription | 1 |
| Epigenetic regulation of adipogenesis genes by MLL3 and MLL4 complexes | 1 |
| MITF-M-dependent gene expression | 1 |
| MITF-M-regulated melanocyte development | 1 |
| Circadian clock | 1 |
| RNA Polymerase II Transcription | 1 |
| Cellular responses to stimuli | 1 |
| Epigenetic regulation of gene expression | 1 |
| Generic Transcription Pathway | 1 |
GO top-level categories
Rollup of top GO terms by namespace:
| Category | Terms |
|---|---|
| cellular anatomical structure | 5 |
| protein binding | 4 |
| DNA repair | 2 |
| negative regulation of DNA-templated transcription | 2 |
| transcription coregulator activity | 2 |
| catalytic activity | 2 |
| enzyme regulator activity | 2 |
| histone deacetylase activity, NAD-dependent | 2 |
| histone H3K deacetylase activity | 2 |
| chromatin | 2 |
| nucleolus | 2 |
| intracellular membrane-bounded organelle | 2 |
| nuclear lumen | 2 |
| cytoplasm | 2 |
| regulation of transcription by RNA polymerase II | 1 |
| transcription by RNA polymerase II | 1 |
| facultative heterochromatin formation | 1 |
| nucleolar chromatin organization | 1 |
| nucleotide-excision repair | 1 |
| pyrimidine dimer repair | 1 |
| DNA biosynthetic process | 1 |
| blood vessel morphogenesis | 1 |
| anatomical structure formation involved in morphogenesis | 1 |
| female gonad development | 1 |
| ovulation cycle process | 1 |
| ovulation | 1 |
| glucose homeostasis | 1 |
| intracellular chemical homeostasis | 1 |
| regulation of protein phosphorylation | 1 |
| protein phosphorylation | 1 |
| positive regulation of protein modification process | 1 |
| positive regulation of phosphorylation | 1 |
| endothelial cell proliferation | 1 |
| regulation of endothelial cell proliferation | 1 |
| positive regulation of epithelial cell proliferation | 1 |
| adaptive immune response | 1 |
| regulation of adaptive immune response | 1 |
| positive regulation of immune response | 1 |
| cellular component organization | 1 |
| constitutive heterochromatin formation | 1 |
Protein interactions and networks
STRING
6954 interactions, top by confidence (×1000):
| Protein A | Protein B | Partner UniProt | Score |
|---|---|---|---|
| SIRT1 | PPARGC1A | Q9UBK2 | 998 |
| SIRT1 | CLOCK | O15516 | 995 |
| SIRT1 | SUV39H1 | O43463 | 990 |
| SIRT1 | NCOR1 | O75376 | 990 |
| SIRT1 | TP53 | P04637 | 990 |
| SIRT1 | ATG5 | Q9H1Y0 | 990 |
| SIRT1 | CDC14A | Q9UNH5 | 989 |
| SIRT1 | BMAL1 | O00327 | 988 |
| SIRT1 | ATG7 | O95352 | 987 |
| SIRT1 | HDAC1 | Q13547 | 987 |
| SIRT1 | F5GZY7 | F5GZY7 | 985 |
| SIRT1 | FOXO1 | Q12778 | 984 |
| SIRT1 | PPARG | P37231 | 981 |
| SIRT1 | CCAR2 | Q8N163 | 977 |
| SIRT1 | GABARAPL2 | P60520 | 973 |
IntAct
524 interactions, top by confidence:
| A | B | Type | Score |
|---|---|---|---|
| SIRT1 | TP53 | psi-mi:“MI:0915”(physical association) | 0.960 |
| SIRT1 | TP53 | psi-mi:“MI:0407”(direct interaction) | 0.960 |
| TP53 | SIRT1 | psi-mi:“MI:0915”(physical association) | 0.960 |
| SIRT1 | CCAR2 | psi-mi:“MI:0915”(physical association) | 0.770 |
| SIRT1 | CCAR2 | psi-mi:“MI:0407”(direct interaction) | 0.770 |
| SIRT1 | CSNK2A1 | psi-mi:“MI:0915”(physical association) | 0.770 |
| SIRT1 | CSNK2A1 | psi-mi:“MI:0407”(direct interaction) | 0.770 |
BioGRID (807): WRN (Biochemical Activity), SIRT1 (Reconstituted Complex), SIRT1 (Affinity Capture-Western), WRN (Affinity Capture-Western), FOXO1 (Affinity Capture-Western), SIRT1 (Affinity Capture-Western), PPARGC1A (Affinity Capture-Western), SIRT1 (Affinity Capture-Western), PPARGC1A (Biochemical Activity), STK11 (Biochemical Activity), SIRT1 (Affinity Capture-Western), RPS19BP1 (Two-hybrid), RPS19BP1 (Reconstituted Complex), RPS19BP1 (Affinity Capture-Western), SIRT1 (Affinity Capture-Western)
ESM2 similar proteins: A0A0G2JZ79, A1ZA92, A6QQR4, A7E2Z2, A8JQ65, A8WRG3, B3NYS4, B4K6T8, B4R0A5, B6VQ60, F4JZ68, O75164, O94640, P06700, P33294, P42124, P50526, P70351, Q04688, Q08BS4, Q14149, Q15910, Q21921, Q28D84, Q28Z18, Q2NKX8, Q4R381, Q4V863, Q5RD88, Q5RDS6, Q5RDX4, Q60L58, Q61188, Q61IS6, Q640I9, Q6DTM3, Q6PL18, Q757M7, Q8CDM1, Q8K3E5
Diamond homologs: A0A0G2JZ79, A8MBU4, B0RM75, B5YJW3, C1DBX3, C6A243, C8V3W5, E9GD30, O07595, O28597, O30124, O58669, O59923, O94640, P06700, P0CS88, P33294, P53685, P53686, P53687, Q21921, Q25337, Q4JBN2, Q4R834, Q4UZX0, Q54GV7, Q54LF0, Q54P49, Q54QE6, Q57V41, Q5A985, Q5AQ47, Q5AW69, Q5HM33, Q5KZE8, Q5L014, Q5RBF1, Q5RJQ4, Q5V4Q5, Q607X6
SIGNOR signaling
83 interactions.
| A | Effect | B | Mechanism |
|---|---|---|---|
| SIRT1 | “up-regulates activity” | FOXO3 | deacetylation |
| SIRT1 | “down-regulates activity” | FOXO3 | deacetylation |
| SIRT1 | up-regulates | FOXO4 | deacetylation |
| SIRT1 | down-regulates | SMAD7 | deacetylation |
| MAPK8 | up-regulates | SIRT1 | phosphorylation |
| FOXL2 | “up-regulates quantity by expression” | SIRT1 | “transcriptional regulation” |
| SIRT1 | down-regulates | FOXL2 | deacetylation |
| SIRT1 | down-regulates | EP300 | deacetylation |
| SIRT1 | down-regulates | TP53 | deacetylation |
| CDK1 | up-regulates | SIRT1 | phosphorylation |
| CSNK2A1 | unknown | SIRT1 | phosphorylation |
| PRKAA1 | up-regulates | SIRT1 | |
| (S)-selisistat | down-regulates | SIRT1 | “chemical inhibition” |
| SIRT1 | up-regulates | CRTC1 | deacetylation |
| SIRT1 | down-regulates | NOTCH1 | deacetylation |
| SRT1720 | “up-regulates activity” | SIRT1 | “chemical activation” |
| SIRT1 | “up-regulates activity” | PPARGC1A | deacetylation |
| CyclinB/CDK1 | up-regulates | SIRT1 | phosphorylation |
| SIRT1 | up-regulates | Cell_cycle_block | |
| SIRT1 | down-regulates | Apoptosis | |
| NAD(1-) | “up-regulates activity” | SIRT1 | binding |
| SIRT1 | “up-regulates quantity” | PPARGC1A | “transcriptional regulation” |
| SIRT1 | “down-regulates activity” | RELA | deacetylation |
| SIRT1 | “up-regulates quantity by expression” | SOD2 | “transcriptional regulation” |
| SIRT1 | up-regulates | FOXO | deacetylation |
Enriched among interaction partners
Reactome pathways and GO biological processes over-represented among this gene’s 143 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.
Reactome pathways:
| Pathway | Partners | Fold | FDR |
|---|---|---|---|
| NOTCH1 Intracellular Domain Regulates Transcription | 5 | 12.1× | 4e-03 |
| Constitutive Signaling by NOTCH1 PEST Domain Mutants | 5 | 10.1× | 5e-03 |
| Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants | 5 | 10.1× | 5e-03 |
| Regulation of PTEN gene transcription | 5 | 9.1× | 7e-03 |
| TCF dependent signaling in response to WNT | 7 | 8.4× | 3e-03 |
| Regulation of PD-L1(CD274) transcription | 6 | 6.7× | 9e-03 |
| Chromatin organization | 7 | 5.8× | 7e-03 |
GO biological processes:
| GO term | Partners | Fold | FDR |
|---|---|---|---|
| outflow tract morphogenesis | 6 | 14.6× | 7e-04 |
| positive regulation of miRNA transcription | 5 | 11.5× | 5e-03 |
| regulation of DNA repair | 5 | 11.0× | 6e-03 |
| canonical Wnt signaling pathway | 9 | 10.9× | 6e-05 |
| rhythmic process | 5 | 10.0× | 7e-03 |
| regulation of protein localization | 6 | 9.8× | 3e-03 |
| double-strand break repair | 6 | 9.7× | 3e-03 |
| anterior/posterior pattern specification | 6 | 8.6× | 5e-03 |
Disease & clinical
Cancer significance
Clinical variants and AI predictions
ClinVar
149 variants total. Per-class counts are floors (≥ shown; pagination cap):
| Classification | Count (floor) |
|---|---|
| Pathogenic | 0 |
| Likely pathogenic | 0 |
| Uncertain significance | 90 |
| Likely benign | 37 |
| Benign | 9 |
Top pathogenic / likely-pathogenic (0)
SpliceAI
1899 predictions. Top by Δscore:
| Variant | Effect | Δscore |
|---|---|---|
| 10:67885115:G:GT | donor_gain | 1.0000 |
| 10:67885118:G:GT | donor_gain | 1.0000 |
| 10:67885148:CGAGG:C | donor_loss | 1.0000 |
| 10:67885150:AG:A | donor_loss | 1.0000 |
| 10:67885151:GG:G | donor_loss | 1.0000 |
| 10:67885152:G:GA | donor_loss | 1.0000 |
| 10:67887529:GA:G | donor_gain | 1.0000 |
| 10:67887530:A:G | donor_gain | 1.0000 |
| 10:67887530:ATAG:A | donor_loss | 1.0000 |
| 10:67887532:AGGT:A | donor_loss | 1.0000 |
| 10:67887533:GG:G | donor_loss | 1.0000 |
| 10:67888469:T:G | donor_gain | 1.0000 |
| 10:67906133:T:G | acceptor_gain | 1.0000 |
| 10:67906775:ATTT:A | acceptor_gain | 1.0000 |
| 10:67906778:T:TA | acceptor_gain | 1.0000 |
| 10:67906782:T:TA | acceptor_gain | 1.0000 |
| 10:67906786:ACAG:A | acceptor_gain | 1.0000 |
| 10:67906787:CAGG:C | acceptor_loss | 1.0000 |
| 10:67906788:A:AG | acceptor_gain | 1.0000 |
| 10:67906788:AG:A | acceptor_gain | 1.0000 |
| 10:67906789:G:GG | acceptor_gain | 1.0000 |
| 10:67906789:GG:G | acceptor_gain | 1.0000 |
| 10:67906789:GGAA:G | acceptor_gain | 1.0000 |
| 10:67906789:GGAAA:G | acceptor_gain | 1.0000 |
| 10:67906921:G:GT | donor_gain | 1.0000 |
| 10:67906938:G:GA | donor_loss | 1.0000 |
| 10:67906938:G:GG | donor_gain | 1.0000 |
| 10:67906939:T:A | donor_loss | 1.0000 |
| 10:67908037:T:TA | acceptor_gain | 1.0000 |
| 10:67908041:TTTAG:T | acceptor_gain | 1.0000 |
AlphaMissense
4901 scored. Top likely-pathogenic:
| Variant | Protein change | am_pathogenicity |
|---|---|---|
| 10:67888897:T:A | V188D | 1.000 |
| 10:67888939:T:C | L202P | 1.000 |
| 10:67888995:T:A | W221R | 1.000 |
| 10:67888995:T:C | W221R | 1.000 |
| 10:67889005:T:A | V224D | 1.000 |
| 10:67889035:G:C | R234T | 1.000 |
| 10:67889035:G:T | R234M | 1.000 |
| 10:67889036:G:C | R234S | 1.000 |
| 10:67889036:G:T | R234S | 1.000 |
| 10:67889107:T:A | V258D | 1.000 |
| 10:67889110:T:C | L259P | 1.000 |
| 10:67889115:G:A | G261R | 1.000 |
| 10:67889115:G:C | G261R | 1.000 |
| 10:67889116:G:A | G261E | 1.000 |
| 10:67889119:C:A | A262D | 1.000 |
| 10:67889121:G:A | G263R | 1.000 |
| 10:67889121:G:C | G263R | 1.000 |
| 10:67889121:G:T | G263W | 1.000 |
| 10:67889122:G:A | G263E | 1.000 |
| 10:67891406:C:T | S265F | 1.000 |
| 10:67891409:T:A | V266D | 1.000 |
| 10:67891421:T:A | I270K | 1.000 |
| 10:67891421:T:C | I270T | 1.000 |
| 10:67891421:T:G | I270R | 1.000 |
| 10:67891426:G:C | D272H | 1.000 |
| 10:67891427:A:C | D272A | 1.000 |
| 10:67891427:A:G | D272G | 1.000 |
| 10:67891427:A:T | D272V | 1.000 |
| 10:67891428:C:A | D272E | 1.000 |
| 10:67891428:C:G | D272E | 1.000 |
dbSNP variants (sampled 300 via entrez): RS1000014826 (10:67905480 A>G), RS1000020014 (10:67908060 G>A), RS1000101106 (10:67897564 ATATT>A), RS1000136797 (10:67913870 A>G), RS1000183558 (10:67890887 G>A,C,T), RS1000184547 (10:67900603 C>T), RS1000324375 (10:67897430 G>C), RS1000376990 (10:67897698 A>G), RS1000487675 (10:67913612 A>T), RS1000517126 (10:67883192 G>A,T), RS1000532127 (10:67918795 C>G,T), RS1000597414 (10:67882799 A>T), RS1000605111 (10:67893007 A>T), RS1000644099 (10:67887738 G>C), RS1000708655 (10:67891589 T>A,C)
Disease associations
OMIM: gene MIM:604479 | disease phenotypes:
GenCC curated gene-disease
| Disease | Classification | Inheritance |
|---|---|---|
| autoimmune disease | Limited | Autosomal dominant |
ClinGen Gene-Disease Validity (1)
Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.
| Disease | Classification | Inheritance |
|---|---|---|
| monogenic diabetes | Limited | AD |
Mondo (1): autoimmune disease (MONDO:0007179)
Orphanet (0):
HPO phenotypes
0 total (0 of 0 shown, HPO-id order):
GWAS associations
5 associations (top):
| Study | Trait | p-value |
|---|---|---|
| GCST002937_4 | Molybdenum levels | 4.000000e-07 |
| GCST006414_136 | Atrial fibrillation | 5.000000e-08 |
| GCST006479_12 | Diverticular disease | 7.000000e-06 |
| GCST006626_41 | Pulse pressure | 2.000000e-10 |
| GCST007576_105 | Chronotype | 3.000000e-09 |
EFO canonical traits (3, from GWAS)
| EFO ID | Trait name |
|---|---|
| EFO:0009959 | diverticular disease |
| EFO:0005763 | pulse pressure measurement |
| EFO:0008328 | chronotype measurement |
MeSH disease descriptors (1)
| Descriptor | Name | Tree numbers |
|---|---|---|
| D001327 | Autoimmune Diseases | C20.111 |
Drugs & pharmacology
Drug and pharmacology data
Is drug target: yes
ChEMBL targets (2): CHEMBL4296132 (PROTEIN-PROTEIN INTERACTION), CHEMBL4506 (SINGLE PROTEIN)
Molecules with ChEMBL bioactivity
6 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 344,421 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).
| Molecule | Name | Phase | Patents |
|---|---|---|---|
| CHEMBL1140 | NIACINAMIDE | 4 | 231,688 |
| CHEMBL165 | RESVERATROL | 3 | 60,144 |
| CHEMBL265502 | SURAMIN | 3 | 36,848 |
| CHEMBL413376 | SURAMIN HEXASODIUM | 3 | 2,743 |
| CHEMBL382277 | EX-527 | 2 | 231 |
| CHEMBL23832 | FENAMIC ACID | 1 | 12,767 |
Clinical evidence (CIViC)
Drug × variant × indication: 1 predictive associations from 1 curated evidence items; also 1 prognostic.
| Variant | Therapy | Indication | Effect | Level | CIViC |
|---|---|---|---|---|---|
| SIRT1 Overexpression | Niacinamide | Pancreatic Cancer | Resistance | CIViC D | EID1294 |
PharmGKB: 1 entry (VIP=true, CPIC=false)
PharmGKB variants
1 variants.
| Variant | Genes | Level | Score | #Clin annots | Drugs |
|---|---|---|---|---|---|
| rs932658 | SIRT1 | 0.00 | 0 |
GtoPdb / IUPHAR curated pharmacology
(IUPHAR/BPS Guide to Pharmacology — expert-curated)
Target class: enzyme — 3.5.1.- Histone deacetylases (HDACs)
Most potent curated ligand interactions (5 total), top 5:
| Ligand | Action | Affinity | Parameter |
|---|---|---|---|
| compound 17 [PMID: 23570514] | Inhibition | 8.17 | pIC50 |
| selisistat | Inhibition | 7.42 | pIC50 |
| SRT1720 | Activation | 6.8 | pEC50 |
| SIRT1 activator 3 | Activation | 6.0 | pIC50 |
| splitomicin | Inhibition | 4.02 | pIC50 |
Binding affinities (BindingDB)
29 measured of 55 human assays (55 total across all organisms); most potent 29 below. Values come from heterogeneous assays and are not directly comparable.
| Ligand | Measure | Value | Patent |
|---|---|---|---|
| 5,5’,5’’-[1,3,6-naphthalenetriyltris(sulfonylimino)]tris[1,3-benzenesulfonate analogue | KI | 25 nM | |
| phenyl N-[1-anilino-6-(heptanethioylamino)-1-oxohexan-2-yl]carbamate | IC50 | 310 nM | US-9359293: Methods of treatment using modulators of SIRT2 |
| 5-(4,6-dihydroxy-1-benzofuran-2-yl)benzene-1,2,3-triol | IC50 | 1840 nM | US-8835659: Polysubstituted benzofurans and medicinal applications thereof |
| phenyl N-[1-anilino-6-(butanethioylamino)-1-oxohexan-2-yl]carbamate | IC50 | 2400 nM | US-9359293: Methods of treatment using modulators of SIRT2 |
| cambinol analog, 6b | IC50 | 12700 nM | |
| CHEBI:5834 | IC50 | 15000 nM | |
| 3-bromo-4-tert-butyl-N-[[4-[5-(dimethylamino)pentanoylamino]phenyl]carbamothioyl]benzamide | IC50 | 18300 nM | US-9365508: Aroyl thiourea derivatives |
| 4-butoxy-3,5-dichloro-N-[[4-[5-(dimethylamino)pentanoylamino]phenyl]carbamothioyl]benzamide | IC50 | 22500 nM | US-9365508: Aroyl thiourea derivatives |
| 3-(4-hydroxyphenyl)-1-benzofuran-4,6-diol | IC50 | 22800 nM | US-8835659: Polysubstituted benzofurans and medicinal applications thereof |
| 3,5-dichloro-N-[[4-[5-(dimethylamino)pentanoylamino]phenyl]carbamothioyl]-4-ethoxybenzamide | IC50 | 29300 nM | US-9365508: Aroyl thiourea derivatives |
| phenyl N-[1-anilino-6-(ethanethioylamino)-1-oxohexan-2-yl]carbamate | IC50 | 30000 nM | US-9359293: Methods of treatment using modulators of SIRT2 |
| 2-(3,5-difluorophenyl)-1-benzofuran-4,6-diol | IC50 | 36700 nM | US-8835659: Polysubstituted benzofurans and medicinal applications thereof |
| cambinol analog, 6xi | IC50 | 38300 nM | |
| 3-bromo-N-[[4-[5-(dimethylamino)pentanoylamino]phenyl]carbamothioyl]benzamide | IC50 | 39900 nM | US-9365508: Aroyl thiourea derivatives |
| cambinol | IC50 | 40700 nM | |
| cambinol analog, 6i | IC50 | 43000 nM | |
| 3-bromo-N-[[4-[5-(dimethylamino)pentanoylamino]phenyl]carbamothioyl]-4-methylbenzamide | IC50 | 43900 nM | US-9365508: Aroyl thiourea derivatives |
| cambinol analog, 6ii | IC50 | 44200 nM | |
| cambinol analog, 6iii | IC50 | 44500 nM | |
| 3,5-dibromo-N-[[4-[5-(dimethylamino)pentanoylamino]phenyl]carbamothioyl]-4-methoxybenzamide | IC50 | 47200 nM | US-9365508: Aroyl thiourea derivatives |
| cambinol analog, 6x | IC50 | 50000 nM | |
| N-[[4-[5-(dimethylamino)pentanoylamino]phenyl]carbamothioyl]-4-methoxy-3-(trifluoromethyl)benzamide | IC50 | 51700 nM | US-9365508: Aroyl thiourea derivatives |
| 4-bromo-N-[[4-[5-(dimethylamino)pentanoylamino]phenyl]carbamothioyl]benzamide | IC50 | 62100 nM | US-9365508: Aroyl thiourea derivatives |
| 3,5-dichloro-N-[[4-[5-(dimethylamino)pentanoylamino]phenyl]carbamothioyl]-4-methoxybenzamide | IC50 | 62500 nM | US-9365508: Aroyl thiourea derivatives |
| N-[[4-[5-(dimethylamino)pentanoylamino]phenyl]carbamothioyl]-4-propan-2-ylbenzamide | IC50 | 64800 nM | US-9365508: Aroyl thiourea derivatives |
| 3,4-dichloro-N-[[4-[5-(dimethylamino)pentanoylamino]phenyl]carbamothioyl]benzamide | IC50 | 70900 nM | US-9365508: Aroyl thiourea derivatives |
| 2-bromo-3-(3,5-difluorophenyl)-1-benzofuran-4,6-diol | IC50 | 76300 nM | US-8835659: Polysubstituted benzofurans and medicinal applications thereof |
| 3-(4-fluorophenyl)-1-benzofuran-4,6-diol | IC50 | 192000 nM | US-8835659: Polysubstituted benzofurans and medicinal applications thereof |
| 3-(3,5-difluorophenyl)-1-benzofuran-4,6-diol | IC50 | 274000 nM | US-8835659: Polysubstituted benzofurans and medicinal applications thereof |
ChEMBL bioactivities
488 potent at pChembl≥5 of 928 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).
| pChembl | Type | Value | Unit | Molecule |
|---|---|---|---|---|
| 8.64 | IC50 | 2.3 | nM | CHEMBL3781397 |
| 8.44 | IC50 | 3.6 | nM | CHEMBL2332039 |
| 8.44 | IC50 | 3.6 | nM | CHEMBL5614132 |
| 8.37 | IC50 | 4.3 | nM | CHEMBL2338810 |
| 8.28 | IC50 | 5.3 | nM | CHEMBL2332037 |
| 8.24 | IC50 | 5.8 | nM | CHEMBL2332043 |
| 8.22 | IC50 | 6 | nM | CHEMBL420311 |
| 8.17 | IC50 | 6.7 | nM | CHEMBL2332041 |
| 7.85 | IC50 | 14 | nM | CHEMBL2332042 |
| 7.82 | IC50 | 15 | nM | CHEMBL2332055 |
| 7.77 | IC50 | 17 | nM | CHEMBL2332044 |
| 7.58 | IC50 | 26 | nM | CHEMBL4438193 |
| 7.57 | IC50 | 27 | nM | SURAMIN |
| 7.51 | IC50 | 31 | nM | CHEMBL2332040 |
| 7.46 | IC50 | 35 | nM | SURAMIN |
| 7.43 | IC50 | 37.1 | nM | CHEMBL3781129 |
| 7.42 | IC50 | 38 | nM | CHEMBL420311 |
| 7.41 | IC50 | 38.7 | nM | CHEMBL3781226 |
| 7.38 | IC50 | 42 | nM | CHEMBL2338808 |
| 7.33 | IC50 | 47 | nM | CHEMBL3779989 |
| 7.32 | IC50 | 48 | nM | CHEMBL4447813 |
| 7.32 | IC50 | 48 | nM | CHEMBL420311 |
| 7.30 | IC50 | 50 | nM | CHEMBL4446458 |
| 7.28 | IC50 | 53 | nM | CHEMBL2338814 |
| 7.25 | IC50 | 56 | nM | CHEMBL2332052 |
| 7.25 | IC50 | 56.8 | nM | CHEMBL3780405 |
| 7.23 | IC50 | 59 | nM | CHEMBL2338816 |
| 7.20 | IC50 | 63.5 | nM | CHEMBL3780552 |
| 7.20 | IC50 | 63 | nM | CHEMBL198609 |
| 7.17 | IC50 | 67 | nM | CHEMBL2332038 |
| 7.15 | IC50 | 71 | nM | CHEMBL4447813 |
| 7.12 | IC50 | 75.2 | nM | CHEMBL3781485 |
| 7.08 | IC50 | 84 | nM | CHEMBL4529328 |
| 7.07 | IC50 | 85 | nM | CHEMBL420311 |
| 7.03 | IC50 | 93 | nM | CHEMBL3951539 |
| 7.03 | IC50 | 93 | nM | CHEMBL4632578 |
| 7.01 | IC50 | 98 | nM | CHEMBL420311 |
| 7.01 | IC50 | 98 | nM | CHEMBL2312289 |
| 7.01 | IC50 | 98 | nM | CHEMBL4457496 |
| 7.01 | IC50 | 98 | nM | EX-527 |
| 7.01 | IC50 | 98 | nM | CHEMBL1797750 |
| 7.00 | IC50 | 100 | nM | CHEMBL420311 |
| 7.00 | Ki | 100 | nM | CHEMBL1410976 |
| 7.00 | IC50 | 100 | nM | CHEMBL4787472 |
| 6.96 | IC50 | 110 | nM | CHEMBL2338813 |
| 6.96 | IC50 | 110 | nM | CHEMBL2332045 |
| 6.96 | IC50 | 110 | nM | CHEMBL3986181 |
| 6.96 | IC50 | 110 | nM | CHEMBL1450796 |
| 6.96 | IC50 | 110 | nM | CHEMBL4855963 |
| 6.96 | IC50 | 110 | nM | CHEMBL5592160 |
PubChem BioAssay actives
476 with measured affinity, of 3537 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.
| Compound | Assay | Type | Value | Unit |
|---|---|---|---|---|
| (2S,5S,8S,33S)-33-acetamido-2-(4-aminobutyl)-N-[(2S)-1-amino-4-methylsulfanyl-1-oxobutan-2-yl]-5-[4-(ethanethioylamino)butyl]-3,6,14,17,24,27,34-heptaoxo-1,4,7,13,16,25,28-heptazacyclotetratriacontane-8-carboxamide | 1286977: Inhibition of recombinant GST-tagged human SIRT1 using 0.3 mM H2N-HK-[N(epsilon)-acetyl-lysine]-LM-COOH as substrate measured after 10 mins HPLC analysis in presence of 0.5 mM beta-NAD+ | ic50 | 0.0023 | uM |
| 4-[4-[2-[[5-(ethylcarbamothioyl)thiophene-2-carbonyl]amino]ethyl]piperidin-1-yl]thieno[3,2-d]pyrimidine-6-carboxamide | 2125908: Inhibition of SIRT1 (unknown origin) | ic50 | 0.0036 | uM |
| 2-N-[2-[1-(6-carbamoylthieno[3,2-d]pyrimidin-4-yl)piperidin-4-yl]ethyl]-5-N-ethylthiophene-2,5-dicarboxamide | 735750: Inhibition of His-tagged SIRT1 (1 to 747) (unknown origin)-mediated deacetylation of Ac-RHKKAcW-NH2 substrate preincubated for 20 mins measured after 30 mins by mass spectrophotometric analysis | ic50 | 0.0036 | uM |
| 4-[4-[2-(methanesulfonamido)ethyl]piperidin-1-yl]thieno[3,2-d]pyrimidine-6-carboxamide | 735750: Inhibition of His-tagged SIRT1 (1 to 747) (unknown origin)-mediated deacetylation of Ac-RHKKAcW-NH2 substrate preincubated for 20 mins measured after 30 mins by mass spectrophotometric analysis | ic50 | 0.0043 | uM |
| 3-N-[2-[1-(6-carbamoylthieno[3,2-d]pyrimidin-4-yl)piperidin-4-yl]ethyl]-1-N-ethylbenzene-1,3-dicarboxamide | 735750: Inhibition of His-tagged SIRT1 (1 to 747) (unknown origin)-mediated deacetylation of Ac-RHKKAcW-NH2 substrate preincubated for 20 mins measured after 30 mins by mass spectrophotometric analysis | ic50 | 0.0053 | uM |
| 4-[4-[2-(thiophene-2-carbonylamino)ethyl]piperidin-1-yl]thieno[3,2-d]pyrimidine-6-carboxamide | 735750: Inhibition of His-tagged SIRT1 (1 to 747) (unknown origin)-mediated deacetylation of Ac-RHKKAcW-NH2 substrate preincubated for 20 mins measured after 30 mins by mass spectrophotometric analysis | ic50 | 0.0058 | uM |
| 6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide | 1690943: Inhibition of human N-terminal His-tagged SIRT1 (183 to 664 residues) expressed in Escherichia coli using Ac-Arg-Leu-Ile-Lys(Ac)-AMC as substrate preincubated for 10 mins followed by substrate addition and measured after 30 mins in presence of NAD+ by fluorescence assay | ic50 | 0.0060 | uM |
| tert-butyl 5-[2-[1-(6-carbamoylthieno[3,2-d]pyrimidin-4-yl)piperidin-4-yl]ethylcarbamoyl]thiophene-2-carboxylate | 735750: Inhibition of His-tagged SIRT1 (1 to 747) (unknown origin)-mediated deacetylation of Ac-RHKKAcW-NH2 substrate preincubated for 20 mins measured after 30 mins by mass spectrophotometric analysis | ic50 | 0.0067 | uM |
| 5-[2-[1-(6-carbamoylthieno[3,2-d]pyrimidin-4-yl)piperidin-4-yl]ethylcarbamoyl]thiophene-2-carboxylic acid | 735750: Inhibition of His-tagged SIRT1 (1 to 747) (unknown origin)-mediated deacetylation of Ac-RHKKAcW-NH2 substrate preincubated for 20 mins measured after 30 mins by mass spectrophotometric analysis | ic50 | 0.0140 | uM |
| 4-[4-[2-(2,2-dimethylpropanoylamino)ethyl]piperidin-1-yl]thieno[3,2-d]pyrimidine-6-carboxamide | 735750: Inhibition of His-tagged SIRT1 (1 to 747) (unknown origin)-mediated deacetylation of Ac-RHKKAcW-NH2 substrate preincubated for 20 mins measured after 30 mins by mass spectrophotometric analysis | ic50 | 0.0150 | uM |
| tert-butyl N-[2-[1-(6-carbamoylthieno[3,2-d]pyrimidin-4-yl)piperidin-4-yl]ethyl]carbamate | 735750: Inhibition of His-tagged SIRT1 (1 to 747) (unknown origin)-mediated deacetylation of Ac-RHKKAcW-NH2 substrate preincubated for 20 mins measured after 30 mins by mass spectrophotometric analysis | ic50 | 0.0170 | uM |
| (2S)-2-[[(2S,3S)-2-[[(2S)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-3-methylpentanoyl]amino]-N-[(2S)-1-[[(2S)-1-amino-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]-6-(tetradecanethioylamino)hexanamide | 1509515: Inhibition of recombinant human C-terminal His6-tagged SIRT1 (Met1 to Ser747 residues) demyristoylase activity expressed in Escherichia coli using p53(Myr)-AMC as substrate measured after 3 hrs in presence of NAD+ and trypsin by fluorescence assay | ic50 | 0.0260 | uM |
| 8-[4-methyl-3-[(5Z)-5-[(Z)-[5-[[2-methyl-5-[(4,6,8-trisulfo-2H-naphthalen-1-ylidene)carbamoyl]cyclohexa-2,4-dien-1-ylidene]carbamoyl]cyclohexa-2,4-dien-1-ylidene]carbamoyl]iminocyclohexa-1,3-diene-1-carbonyl]iminocyclohexa-1,4-diene-1-carbonyl]imino-7H-naphthalene-1,3,5-trisulfonic acid | 1690943: Inhibition of human N-terminal His-tagged SIRT1 (183 to 664 residues) expressed in Escherichia coli using Ac-Arg-Leu-Ile-Lys(Ac)-AMC as substrate preincubated for 10 mins followed by substrate addition and measured after 30 mins in presence of NAD+ by fluorescence assay | ic50 | 0.0270 | uM |
| 2-N-[2-[4-(6-carbamoylthieno[3,2-d]pyrimidin-4-yl)piperazin-1-yl]ethyl]-5-N-ethylthiophene-2,5-dicarboxamide | 735750: Inhibition of His-tagged SIRT1 (1 to 747) (unknown origin)-mediated deacetylation of Ac-RHKKAcW-NH2 substrate preincubated for 20 mins measured after 30 mins by mass spectrophotometric analysis | ic50 | 0.0310 | uM |
| (2S,5S,8S,27S)-27-acetamido-2-(4-aminobutyl)-N-[(2S)-1-amino-4-methylsulfanyl-1-oxobutan-2-yl]-5-[4-(ethanethioylamino)butyl]-3,6,14,21,28-pentaoxo-1,4,7,13,22-pentazacyclooctacosane-8-carboxamide | 1286977: Inhibition of recombinant GST-tagged human SIRT1 using 0.3 mM H2N-HK-[N(epsilon)-acetyl-lysine]-LM-COOH as substrate measured after 10 mins HPLC analysis in presence of 0.5 mM beta-NAD+ | ic50 | 0.0371 | uM |
| (2S,5S,8S,31S)-31-acetamido-2-(4-aminobutyl)-N-[(2S)-1-amino-4-methylsulfanyl-1-oxobutan-2-yl]-5-[4-(ethanethioylamino)butyl]-3,6,14,17,22,25,32-heptaoxo-1,4,7,13,16,23,26-heptazacyclodotriacontane-8-carboxamide | 1286977: Inhibition of recombinant GST-tagged human SIRT1 using 0.3 mM H2N-HK-[N(epsilon)-acetyl-lysine]-LM-COOH as substrate measured after 10 mins HPLC analysis in presence of 0.5 mM beta-NAD+ | ic50 | 0.0387 | uM |
| 4-[4-[3-(2,2-dimethylpropanoylamino)propyl]piperidin-1-yl]thieno[3,2-d]pyrimidine-6-carboxamide | 735750: Inhibition of His-tagged SIRT1 (1 to 747) (unknown origin)-mediated deacetylation of Ac-RHKKAcW-NH2 substrate preincubated for 20 mins measured after 30 mins by mass spectrophotometric analysis | ic50 | 0.0420 | uM |
| (3R,6S,9S,12S,15S,18S,21S,24S,27S,30S,33S,36S,39R,42S)-12,36-bis(2-amino-2-oxoethyl)-33-benzyl-27-[(2S)-butan-2-yl]-21,30-bis(3-carbamimidamidopropyl)-6,9,15,39-tetrakis(hydroxymethyl)-18,42-bis[(4-hydroxyphenyl)methyl]-5,8,11,14,17,20,23,26,29,32,35,38,41,44-tetradecaoxo-24-[4-[(2,2,2-trifluoroacetyl)amino]butyl]-1-thia-4,7,10,13,16,19,22,25,28,31,34,37,40,43-tetradecazacyclopentatetracontane-3-carboxamide | 1286968: Inhibition of SIRT1 (unknown origin) | ic50 | 0.0470 | uM |
| (2S)-2-[[(2S,3S)-2-[[(2S)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-3-methylpentanoyl]amino]-N-[(2S)-1-[[(2S)-1-amino-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]-6-[[2-(4-phenyldiazenylphenyl)acetyl]amino]hexanamide | 1509508: Inhibition of recombinant human C-terminal His6-tagged SIRT1 (Met1 to Ser747 residues) defatty-acylase activity expressed in Escherichia coli using SFP3 as substrate measured at 5 mins interval for 60 mins in presence of NAD+ by fluorescence assay | ic50 | 0.0480 | uM |
| (2S)-2-[[(2S,3S)-2-[[(2S)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-3-methylpentanoyl]amino]-N-[(2S)-1-[[(2S)-1-amino-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]-6-[[2-[4-[(4-hydroxyphenyl)diazenyl]phenyl]acetyl]amino]hexanamide | 1509515: Inhibition of recombinant human C-terminal His6-tagged SIRT1 (Met1 to Ser747 residues) demyristoylase activity expressed in Escherichia coli using p53(Myr)-AMC as substrate measured after 3 hrs in presence of NAD+ and trypsin by fluorescence assay | ic50 | 0.0500 | uM |
| 4-[4-(2-pyrrolidin-1-ylethyl)piperazin-1-yl]thieno[3,2-d]pyrimidine-6-carboxamide | 735750: Inhibition of His-tagged SIRT1 (1 to 747) (unknown origin)-mediated deacetylation of Ac-RHKKAcW-NH2 substrate preincubated for 20 mins measured after 30 mins by mass spectrophotometric analysis | ic50 | 0.0530 | uM |
| 4-[4-[2-(ethanethioylamino)ethyl]piperidin-1-yl]thieno[3,2-d]pyrimidine-6-carboxamide | 735750: Inhibition of His-tagged SIRT1 (1 to 747) (unknown origin)-mediated deacetylation of Ac-RHKKAcW-NH2 substrate preincubated for 20 mins measured after 30 mins by mass spectrophotometric analysis | ic50 | 0.0560 | uM |
| (2S,5S,8S,29S)-29-acetamido-2-(4-aminobutyl)-N-[(2S)-1-amino-4-methylsulfanyl-1-oxobutan-2-yl]-5-[4-(ethanethioylamino)butyl]-3,6,14,17,20,23,30-heptaoxo-1,4,7,13,16,21,24-heptazacyclotriacontane-8-carboxamide | 1286977: Inhibition of recombinant GST-tagged human SIRT1 using 0.3 mM H2N-HK-[N(epsilon)-acetyl-lysine]-LM-COOH as substrate measured after 10 mins HPLC analysis in presence of 0.5 mM beta-NAD+ | ic50 | 0.0568 | uM |
| 7-[4-[2-(2,2-dimethylpropanoylamino)ethyl]piperidin-1-yl]thieno[3,2-b]pyridine-2-carboxamide | 735750: Inhibition of His-tagged SIRT1 (1 to 747) (unknown origin)-mediated deacetylation of Ac-RHKKAcW-NH2 substrate preincubated for 20 mins measured after 30 mins by mass spectrophotometric analysis | ic50 | 0.0590 | uM |
| (6S)-2-chloro-5,6,7,8,9,10-hexahydrocyclohepta[b]indole-6-carboxamide | 256743: Inhibitory activity against recombinant human SIRT1 expressed in Escherichia coli by fluorimetric assay | ic50 | 0.0630 | uM |
| (2S,5S,8S,25S)-25-acetamido-2-(4-aminobutyl)-N-[(2S)-1-amino-4-methylsulfanyl-1-oxobutan-2-yl]-5-[4-(ethanethioylamino)butyl]-3,6,14,19,26-pentaoxo-1,4,7,13,20-pentazacyclohexacosane-8-carboxamide | 1286977: Inhibition of recombinant GST-tagged human SIRT1 using 0.3 mM H2N-HK-[N(epsilon)-acetyl-lysine]-LM-COOH as substrate measured after 10 mins HPLC analysis in presence of 0.5 mM beta-NAD+ | ic50 | 0.0635 | uM |
| 3-N-[2-[4-(6-carbamoylthieno[3,2-d]pyrimidin-4-yl)piperazin-1-yl]ethyl]-1-N-ethylbenzene-1,3-dicarboxamide | 735750: Inhibition of His-tagged SIRT1 (1 to 747) (unknown origin)-mediated deacetylation of Ac-RHKKAcW-NH2 substrate preincubated for 20 mins measured after 30 mins by mass spectrophotometric analysis | ic50 | 0.0670 | uM |
| (2S,5S,8S,23S)-23-acetamido-2-(4-aminobutyl)-N-[(2S)-1-amino-4-methylsulfanyl-1-oxobutan-2-yl]-5-[4-(ethanethioylamino)butyl]-3,6,14,17,24-pentaoxo-1,4,7,13,18-pentazacyclotetracosane-8-carboxamide | 1286977: Inhibition of recombinant GST-tagged human SIRT1 using 0.3 mM H2N-HK-[N(epsilon)-acetyl-lysine]-LM-COOH as substrate measured after 10 mins HPLC analysis in presence of 0.5 mM beta-NAD+ | ic50 | 0.0752 | uM |
| (2S)-2-[[(2S,3S)-2-acetamido-3-methylpentanoyl]amino]-N-[(2S)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]-6-[[2-(4-phenyldiazenylphenyl)acetyl]amino]hexanamide | 1509515: Inhibition of recombinant human C-terminal His6-tagged SIRT1 (Met1 to Ser747 residues) demyristoylase activity expressed in Escherichia coli using p53(Myr)-AMC as substrate measured after 3 hrs in presence of NAD+ and trypsin by fluorescence assay | ic50 | 0.0840 | uM |
| hexasodium;8-[[3-[[3-[[3-amino-5-[[3-[(4,6,8-trisulfonatonaphthalen-1-yl)carbamoyl]phenyl]carbamoyl]phenyl]carbamoylamino]benzoyl]amino]benzoyl]amino]naphthalene-1,3,5-trisulfonate | 1317161: Inhibition of full-length human N-terminal GST-tagged SIRT1 expressed in Escherichia coli BL21 (DE3) assessed as inhibition of deacetylase activity using ZMAL as substrate measured after 4 hrs by Fluor de Lys assay | ic50 | 0.0930 | uM |
| hexasodium;8-[[3-[[3-amino-5-[[3-[(4,6,8-trisulfonatonaphthalen-1-yl)carbamoyl]phenyl]carbamoyl]benzoyl]amino]benzoyl]amino]naphthalene-1,3,5-trisulfonate | 1652959: Inhibition of sirtuin 1 (unknown origin) | ic50 | 0.0930 | uM |
| (2S)-2-[[(2S,3S)-2-[[(2S)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-3-methylpentanoyl]amino]-N-[(2S)-1-[[(2S)-1-amino-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]-6-[[2-[4-[[4-(dimethylamino)phenyl]diazenyl]phenyl]acetyl]amino]hexanamide | 1509515: Inhibition of recombinant human C-terminal His6-tagged SIRT1 (Met1 to Ser747 residues) demyristoylase activity expressed in Escherichia coli using p53(Myr)-AMC as substrate measured after 3 hrs in presence of NAD+ and trypsin by fluorescence assay | ic50 | 0.0980 | uM |
| 6-chloro-2,3,4,4a,9,9a-hexahydro-1H-carbazole-1-carboxamide | 1617832: Inhibition of SIRT1 (unknown origin) | ic50 | 0.0980 | uM |
| 8-methyl-1-(4-methylphenyl)-2,4-dihydro-1H-benzo[f]quinolin-3-one | 602654: Inhibition of SIRT1 | ic50 | 0.0980 | uM |
| (1R)-6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide | 725328: Inhibition of full length SIRT1 (unknown origin) by fluorometric enzyme assay | ic50 | 0.0980 | uM |
| 5-[(3-bromo-4-hydroxy-5-methoxyphenyl)methylidene]-2-phenyl-1,3-dioxane-4,6-dione | 1694708: Inhibition of wild type N-terminal hexa-His-tagged human SIRT1 (156 to 664 residues) expressed in Escherichia coli BL21 (DE3) assessed as dissociation equilibrium constant using Abz-GVLKacAYNO2GY-NH2 as substrate in presence of varying level of NAD+ by Lineweaver-burk plot analysis | ki | 0.1000 | uM |
| 1-phenothiazin-10-yl-2-(5H-[1,2,4]triazino[5,6-b]indol-3-ylsulfanyl)butan-1-one | 1694722: Inhibition of His-tagged SIRT1 (unknown origin) expressed in Escherichia coli codon plus (DE3) using acetylated p53 as substrate | ic50 | 0.1000 | uM |
| 4-[(2-cyanophenyl)methyl]-2,3-dihydro-1,4-benzoxazine-2-carboxamide | 1776280: Inhibition of His6-tagged SIRT1 (unknown origin) expressed in Escherichia coli BL21 (DE3) preincubated for 15 mins followed by NAD+ addition and measured after 30 mins by FLucK529Ac based luminescence assay | ic50 | 0.1100 | uM |
| triethyl-[[3-[[(2S)-2-(phenylmethoxycarbonylamino)-6-(tetradecanethioylamino)hexanoyl]amino]phenyl]methyl]azanium bromide | 2117958: Inhibition of human SIRT1 preincubated for 15 mins followed by H3K9Ac (KQTARK(Ac)STGGWW) peptide addition and measured after 5 mins | ic50 | 0.1100 | uM |
| 3-butyl-1,6-dimethylpyrimido[5,4-e][1,2,4]triazine-5,7-dione | 1317182: Inhibition of human SIRT1 using biotinylated peptide with an acetylated FLAG sequence as substrate measured after 3 hr in presence of NAD+ by TR-FRET assay | ic50 | 0.1100 | uM |
| 1,6-dimethyl-3-(4-methylphenyl)pyrimido[5,4-e][1,2,4]triazine-5,7-dione | 1317182: Inhibition of human SIRT1 using biotinylated peptide with an acetylated FLAG sequence as substrate measured after 3 hr in presence of NAD+ by TR-FRET assay | ic50 | 0.1100 | uM |
| 4-[4-(2-acetamidoethyl)piperidin-1-yl]thieno[3,2-d]pyrimidine-6-carboxamide | 735750: Inhibition of His-tagged SIRT1 (1 to 747) (unknown origin)-mediated deacetylation of Ac-RHKKAcW-NH2 substrate preincubated for 20 mins measured after 30 mins by mass spectrophotometric analysis | ic50 | 0.1100 | uM |
| 4-[4-(2-pyrrolidin-1-ylethyl)piperidin-1-yl]thieno[3,2-d]pyrimidine-6-carboxamide | 735750: Inhibition of His-tagged SIRT1 (1 to 747) (unknown origin)-mediated deacetylation of Ac-RHKKAcW-NH2 substrate preincubated for 20 mins measured after 30 mins by mass spectrophotometric analysis | ic50 | 0.1100 | uM |
| 2-[2-(1H-indol-3-yl)ethyl]-1-methylquinolin-1-ium-4-amine | 1938012: Inhibition of SIRT1 (unknown origin) | ic50 | 0.1200 | uM |
| 4-[4-[2-(2,2-dimethylpropanoylamino)ethyl]piperazin-1-yl]thieno[3,2-d]pyrimidine-6-carboxamide | 735750: Inhibition of His-tagged SIRT1 (1 to 747) (unknown origin)-mediated deacetylation of Ac-RHKKAcW-NH2 substrate preincubated for 20 mins measured after 30 mins by mass spectrophotometric analysis | ic50 | 0.1200 | uM |
| 2-chloro-5,6,7,8,9,10-hexahydrocyclohepta[b]indole-6-carboxamide | 256743: Inhibitory activity against recombinant human SIRT1 expressed in Escherichia coli by fluorimetric assay | ic50 | 0.1240 | uM |
| (2S)-2-[[(2S,3S)-2-[[(2S)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-3-methylpentanoyl]amino]-N-[(2S)-1-[[(2S)-1-amino-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]-6-[[2-[4-[[4-(diethylamino)phenyl]diazenyl]phenyl]acetyl]amino]hexanamide | 1509515: Inhibition of recombinant human C-terminal His6-tagged SIRT1 (Met1 to Ser747 residues) demyristoylase activity expressed in Escherichia coli using p53(Myr)-AMC as substrate measured after 3 hrs in presence of NAD+ and trypsin by fluorescence assay | ic50 | 0.1400 | uM |
| 6-chloro-N-(dimethylaminomethylidene)-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide | 1317171: Inhibition of recombinant SIRT1 (unknown origin) assessed as deacetylation activity using acetylated p53 as substrate measured after 2 hrs by Fluor de Lys assay | ic50 | 0.1490 | uM |
| 4-[(2-nitrophenyl)methyl]-2,3-dihydro-1,4-benzoxazine-2-carboxamide | 1776280: Inhibition of His6-tagged SIRT1 (unknown origin) expressed in Escherichia coli BL21 (DE3) preincubated for 15 mins followed by NAD+ addition and measured after 30 mins by FLucK529Ac based luminescence assay | ic50 | 0.1500 | uM |
| N-[2-[3-(piperazin-1-ylmethyl)imidazo[2,1-b][1,3]thiazol-6-yl]phenyl]quinoxaline-2-carboxamide | 1934120: Inhibition of SIRT1 (unknown origin) | ec50 | 0.1600 | uM |
CTD chemical–gene interactions
261 total (human), top 30 by PubMed support.
| Chemical | Actions (top 5) | PubMed papers |
|---|---|---|
| Resveratrol | decreases response to substance, increases stability, affects response to substance, decreases abundance, increases abundance (+20 more) | 83 |
| sirtinol | decreases activity, decreases reaction, affects cotreatment, affects binding, increases acetylation (+5 more) | 19 |
| Glucose | affects reaction, affects cotreatment, increases expression, affects binding, decreases activity (+12 more) | 19 |
| 6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide | decreases expression, decreases reaction, increases expression, increases activity, increases secretion (+4 more) | 18 |
| Hydrogen Peroxide | increases activity, decreases response to substance, increases expression, affects reaction, decreases activity (+11 more) | 16 |
| Niacinamide | affects cotreatment, decreases reaction, increases reaction, decreases acetylation, increases phosphorylation (+5 more) | 16 |
| Lipopolysaccharides | decreases expression, increases expression, affects cotreatment, affects expression, increases secretion (+5 more) | 9 |
| SRT1720 | affects reaction, decreases expression, decreases reaction, decreases activity, increases activity (+2 more) | 8 |
| sodium arsenite | affects binding, increases abundance, decreases expression, decreases reaction, increases expression (+3 more) | 7 |
| N-(oxo-5,6-dihydrophenanthridin-2-yl)-N,N-dimethylacetamide hydrochloride | increases expression, increases response to substance, decreases expression, decreases reaction, decreases activity (+2 more) | 5 |
| dorsomorphin | affects cotreatment, decreases expression, decreases reaction, increases expression | 5 |
| Cisplatin | increases expression, increases reaction, increases response to substance, affects reaction, affects cotreatment (+2 more) | 5 |
| Oxygen | increases cleavage, affects response to substance, increases expression, increases reaction, affects reaction (+7 more) | 5 |
| Valproic Acid | affects expression, decreases expression, decreases methylation | 5 |
| bisphenol A | decreases expression, decreases reaction, increases expression, affects cotreatment | 4 |
| Dexamethasone | affects cotreatment, decreases expression, decreases reaction, affects reaction, increases expression (+2 more) | 4 |
| Doxorubicin | decreases expression, decreases reaction, affects reaction, affects response to substance, decreases response to substance (+1 more) | 4 |
| 1-Methyl-4-phenylpyridinium | decreases reaction, affects reaction, increases expression, decreases activity, decreases expression | 4 |
| arsenite | affects binding, decreases reaction, increases reaction, decreases expression, increases expression (+1 more) | 3 |
| N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide | decreases reaction, increases expression, affects cotreatment, decreases expression | 3 |
| Acetaminophen | affects response to substance, increases expression, decreases reaction, affects reaction | 3 |
| Acetylcysteine | decreases expression, decreases reaction | 3 |
| Ethanol | decreases expression, decreases reaction, increases reaction | 3 |
| Estradiol | decreases expression, decreases reaction, affects binding, increases reaction | 3 |
| Melatonin | decreases expression, decreases reaction, decreases activity | 3 |
| NAD | decreases activity, increases abundance, increases activity, decreases reaction, increases reaction (+4 more) | 3 |
| Quercetin | increases activity, increases expression, affects reaction, decreases expression, decreases reaction | 3 |
| Dinoprostone | decreases expression, decreases reaction, affects binding, increases reaction, increases abundance (+4 more) | 3 |
| Palmitic Acid | decreases activity, decreases reaction, decreases expression, increases oxidation, increases acetylation (+5 more) | 3 |
| baicalein | decreases reaction, increases expression, affects expression, decreases expression, affects cotreatment (+3 more) | 2 |
ChEMBL screening assays
645 unique, capped per target: 642 binding, 3 admet
Representative assays (with source publication via chembl_document):
| Assay ID | Type | Description | Source paper |
|---|---|---|---|
| CHEMBL4219423 | Binding | Induction of cereblon-mediated Sirt1 degradation in human HeLa cells at 10 uM after 1 to 6 hrs by Western blot method | Chemically Induced Degradation of Sirtuin 2 (Sirt2) by a Proteolysis Targeting Chimera (PROTAC) Based on Sirtuin Rearranging Ligands (SirReals). — J Med Chem |
| CHEMBL4322654 | ADMET | Inhibition of human sirtuin 1 at 25 uM relative to control | Structure-Reactivity Relationships on Substrates and Inhibitors of the Lysine Deacylase Sirtuin 2 from Schistosoma mansoni (SmSirt2). — J Med Chem |
Cellosaurus cell lines
21 cell lines: 18 cancer cell line, 3 transformed cell line
First 10 cell lines (id-ordered, not curated):
| Cellosaurus | Name | Category | Sex |
|---|---|---|---|
| CVCL_A6UK | COLO 320DM#3 SIRT1 KO cl.1 | Cancer cell line | Female |
| CVCL_A6UL | COLO 320DM#3 SIRT1 KO cl.2 | Cancer cell line | Female |
| CVCL_A6UM | COLO 320DM#3 SIRT1 KO cl.3 | Cancer cell line | Female |
| CVCL_A6UN | COLO 320DM#3 SIRT1 KO cl.4 | Cancer cell line | Female |
| CVCL_A6UP | COLO 320DM#3 SIRT1 KO cl.5 | Cancer cell line | Female |
| CVCL_A6UQ | COLO 320DM#3 SIRT1 KO cl.6 | Cancer cell line | Female |
| CVCL_B1BH | Abcam HEK293 SIRT1 KO | Transformed cell line | Female |
| CVCL_B8PC | Abcam HCT 116 SIRT1 KO | Cancer cell line | Male |
| CVCL_B9BH | Abcam MCF-7 SIRT1 KO | Cancer cell line | Female |
| CVCL_B9RQ | Abcam A-549 SIRT1 KO | Cancer cell line | Male |
Clinical trials (associated diseases)
300 trials via MONDO — disease-level, not drug-specific.
| Trial | Phase | Status | Title |
|---|---|---|---|
| NCT00001658 | PHASE4 | COMPLETED | Amoxicillin for the Treatment of Pediatric Autoimmune Disorders Associated With Streptococcal Infections |
| NCT00820469 | PHASE4 | COMPLETED | Study of the Influence of Plasma Exchange on the Pharmacokinetics of Rituximab |
| NCT00862693 | PHASE4 | UNKNOWN | Calcitriol in the Treatment of Immunoglobulin A Nephropathy |
| NCT01065285 | PHASE4 | COMPLETED | Vaccination Against Influenza in Autoimmune Diseases |
| NCT04015596 | PHASE4 | TERMINATED | Trial of Naproxen Sodium for the Treatment of OCD in Children With PANDAS |
| NCT04127747 | PHASE4 | UNKNOWN | Efficacy of Individualized Rituximab in Maintaining Remission of Moderate and Severe Systemic Lupus Erythematosus |
| NCT04297592 | PHASE4 | ENROLLING_BY_INVITATION | Antibiotic Prophylaxis in High-Risk Arthroplasty Patients |
| NCT06499233 | PHASE4 | RECRUITING | Efficacy and Safety of Prophylactic Treatment for Pneumocystis Jirovecii Pneumonia in Patients With Autoimmune Inflammatory Rheumatic Disease |
| NCT06723548 | PHASE4 | NOT_YET_RECRUITING | Telitacicept and Low-dose Steroids in Refractory Myasthenia Gravis |
| NCT06964269 | PHASE4 | RECRUITING | Use of Acthar Gel Single-Dose Pre-Filled SelfJectTM Injector in Patients With Moderate-Severe Keratitis and Autoimmune Disease |
| NCT00001768 | PHASE3 | COMPLETED | Treatment of Childhood Onset Psychiatric Disorders With Intravenous Immunoglobulin (IVIg) |
| NCT00035308 | PHASE3 | COMPLETED | Safety and Efficacy Study of LJP 394 (Abetimus Sodium) to Treat Lupus Kidney Disease |
| NCT00351377 | PHASE3 | COMPLETED | Gastrointestinal and Health-related Quality of Life Outcomes in Patients With Autoimmune Diseases Treated With Mycophenolate |
| NCT00419419 | PHASE3 | COMPLETED | Phase III Study of a Topical Gel Formulation for Treatment and Prevention of Raynaud’s Phenomenon |
| NCT01004432 | PHASE3 | COMPLETED | Golimumab in Rheumatoid Arthritis Participants With an Inadequate Response to Etanercept (ENBREL) or Adalimumab (HUMIRA) |
| NCT01196091 | PHASE3 | COMPLETED | A Study of LY2127399 in Participants With Systemic Lupus Erythematosus |
| NCT01205438 | PHASE3 | COMPLETED | A Study of LY2127399 in Participants With Systemic Lupus Erythematosus |
| NCT01210716 | PHASE3 | COMPLETED | Evaluation of Therapeutic Plasma Exchange (TPE) Procedure Using the AMICUS Device |
| NCT01281969 | PHASE3 | COMPLETED | Intravenous Immunoglobulin for PANDAS |
| NCT01488708 | PHASE3 | TERMINATED | On Open-Label Study in Participants With Systemic Lupus Erythematosus |
| NCT01601028 | PHASE3 | COMPLETED | Hydroxychloroquine Treatment of Dry Eyes in Patients With Primary Sjögren’s Syndrome |
| NCT02263703 | PHASE3 | COMPLETED | Immunogenicity of HPV Vaccine in Immunosuppressed Children |
| NCT03790293 | PHASE3 | COMPLETED | Clinical and Immunological Long-term Follow-up of Patients With Pemphigus Included in the RITUXIMAB 3 Trial |
| NCT05069714 | PHASE3 | COMPLETED | One or Two Week Methotrexate Discontinuation on Efficacy of Influenza Vaccination in Rheumatoid Arthritis. |
| NCT00010387 | PHASE2 | COMPLETED | Phase II Study of High-Dose Cyclophosphamide in Patients With Severe Autoimmune Hematologic Disease |
| NCT00716066 | PHASE2 | ACTIVE_NOT_RECRUITING | Autologous Stem Cell Transplant for Neurologic Autoimmune Diseases |
| NCT00977977 | PHASE2 | RECRUITING | Rituximab Plus Cyclosporine in Idiopathic Membranous Nephropathy |
| NCT01579110 | PHASE2 | UNKNOWN | Efficacy and Safety of Levamisole Combined With Standard Prednisolone in Warm Antibody Autoimmune Hemolytic Anemia. |
| NCT01778348 | PHASE2 | COMPLETED | Closing the Loop in Children and Adolescents With Type 1 Diabetes in the Home Setting |
| NCT02203682 | PHASE2 | UNKNOWN | Doxycycline Treatment in Mild Thyroid-Associated Ophthalmopathy |
| NCT02458196 | PHASE2 | UNKNOWN | Study of Treatment Response on IgG4 Related Disease (IgG4RD) |
| NCT02647866 | PHASE2 | COMPLETED | Study of a Monoclonal Antibody KHK4083 in Moderate Ulcerative Colitis |
| NCT02682511 | PHASE2 | ACTIVE_NOT_RECRUITING | Oral Ifetroban to Treat Diffuse Cutaneous Systemic Sclerosis (SSc) or SSc-associated Pulmonary Arterial Hypertension |
| NCT03183869 | PHASE2 | TERMINATED | Fecal Microbial Transplantation in Relapsing Multiple Sclerosis Patients |
| NCT03239600 | PHASE2 | WITHDRAWN | A Study to Evaluate the Safety, Tolerability, Pharmacokinetics (PK), Proof of Mechanism of GSK2618960 in Primary Sjögren’s Syndrome (pSS) |
| NCT03345004 | PHASE2 | COMPLETED | Diamyd Administered Into Lymph Nodes in Combination With Vitamin D in Type 1 Diabetes |
| NCT03644069 | PHASE2 | UNKNOWN | A Study of the Safety, Efficacy and Tolerability of Nexvax-2 in Patients With Celiac Disease (CeD) |
| NCT03651518 | PHASE2 | COMPLETED | Personalized Therapies in Inflammatory Complex Disease |
| NCT04186871 | PHASE2 | COMPLETED | Study to Assess Safety and Effectiveness of Branebrutinib Treatment in Participants With Active Systemic Lupus Erythematosus or Primary Sjögren’s Syndrome, or Branebrutinib Treatment Followed by Open-label Abatacept Treatment in Study Participants With Active Rheumatoid Arthritis |
| NCT04663204 | PHASE2 | ACTIVE_NOT_RECRUITING | A Study of the Safety and Activity of Sparsentan for the Treatment of Incident Patients With Immunoglobulin A Nephropathy |
Related Atlas pages
- Associated diseases: autoimmune disease, monogenic diabetes, malignant pancreatic neoplasm
- Biomarker drugs (CIViC) (drugs whose response is associated with variants in this gene — CIViC predictive evidence, not targeting): Niacinamide
- Disease cohort memberships (association, not causation — diseases whose associated-gene cohort lists this gene; a subset are also under Associated diseases): atrial fibrillation, autoimmune disease, exocrine pancreatic carcinoma, malignant pancreatic neoplasm, pancreatic ductal adenocarcinoma