SIRT5

Summary

SIRT5 (sirtuin 5, HGNC:14933) is a protein-coding gene on chromosome 6p23, encoding NAD-dependent protein deacylase sirtuin-5, mitochondrial (Q9NXA8). NAD-dependent lysine demalonylase, desuccinylase and deglutarylase that specifically removes malonyl, succinyl and glutaryl groups on target proteins.

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 III of the sirtuin family. Alternative splicing of this gene results in multiple transcript variants.

Source: NCBI Gene 23408 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 72 total
• Druggable target: yes — 9 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_012241

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14933
Approved symbol	SIRT5
Name	sirtuin 5
Location	6p23
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000124523
Ensembl biotype	protein_coding
OMIM	604483
Entrez	23408

Gene structure

Transcript identifiers

Ensembl transcripts: 71 — 59 protein_coding, 10 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000359782, ENST00000379250, ENST00000379262, ENST00000397350, ENST00000606117, ENST00000606427, ENST00000637463, ENST00000679658, ENST00000679663, ENST00000679922, ENST00000680151, ENST00000680402, ENST00000680432, ENST00000680442, ENST00000680707, ENST00000680747, ENST00000680754, ENST00000680852, ENST00000680937, ENST00000681012, ENST00000681231, ENST00000681243, ENST00000681818, ENST00000681905, ENST00000888571, ENST00000888572, ENST00000888573, ENST00000888574, ENST00000888575, ENST00000888576, ENST00000888577, ENST00000888578, ENST00000888579, ENST00000888580, ENST00000888581, ENST00000888582, ENST00000888583, ENST00000888584, ENST00000888585, ENST00000888586, ENST00000888587, ENST00000888588, ENST00000888589, ENST00000888590, ENST00000915669, ENST00000915670, ENST00000915671, ENST00000915672, ENST00000915673, ENST00000915674, ENST00000949353, ENST00000949354, ENST00000949355, ENST00000949356, ENST00000949357, ENST00000949358, ENST00000949359, ENST00000949360, ENST00000949361, ENST00000949362, ENST00000949363, ENST00000949364, ENST00000949365, ENST00000949366, ENST00000949367, ENST00000949368, ENST00000949369, ENST00000949370, ENST00000949371, ENST00000949372, ENST00000949373

RefSeq mRNA: 22 — MANE Select: NM_012241 NM_001193267, NM_001242827, NM_001376798, NM_001376799, NM_001376800, NM_001376801, NM_001376802, NM_001376803, NM_001376804, NM_001376805, NM_001376806, NM_001376807, NM_001376808, NM_001376809, NM_001376810, NM_001376811, NM_001376812, NM_001376813, NM_001376814, NM_001376815, NM_012241, NM_031244

CCDS: CCDS4526, CCDS4527, CCDS54966, CCDS93861, CCDS93862

Canonical transcript exons

ENST00000606117 — 10 exons

Exon	Start	End
ENSE00000848043	13588331	13588464
ENSE00001372681	13579451	13579609
ENSE00001374504	13574601	13574744
ENSE00002320942	13611790	13615158
ENSE00003468946	13584076	13584225
ENSE00003695558	13599032	13599155
ENSE00003696738	13591669	13591894
ENSE00003697104	13600834	13600949
ENSE00003702336	13596963	13597016
ENSE00003702348	13595477	13595564

Expression profiles

Bgee: expression breadth ubiquitous, 278 present calls, max score 91.01.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 4.3201 / max 108.5483, expressed in 1569 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
65953	2.3252	1321
65954	1.7966	905
203870	0.1984	86

Top tissues by expression

287 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
diaphragm	UBERON:0001103	91.01	gold quality
apex of heart	UBERON:0002098	90.26	gold quality
heart left ventricle	UBERON:0002084	89.28	gold quality
cardiac ventricle	UBERON:0002082	89.20	gold quality
buccal mucosa cell	CL:0002336	88.49	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	88.25	gold quality
right lobe of liver	UBERON:0001114	88.21	gold quality
liver	UBERON:0002107	88.01	gold quality
body of tongue	UBERON:0011876	87.81	gold quality
hindlimb stylopod muscle	UBERON:0004252	87.77	gold quality
tendon of biceps brachii	UBERON:0008188	87.48	gold quality
biceps brachii	UBERON:0001507	87.13	gold quality
heart	UBERON:0000948	87.09	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	86.92	gold quality
muscle of leg	UBERON:0001383	86.84	gold quality
right atrium auricular region	UBERON:0006631	86.77	gold quality
muscle organ	UBERON:0001630	86.55	gold quality
vastus lateralis	UBERON:0001379	86.54	gold quality
gastrocnemius	UBERON:0001388	86.53	gold quality
cardiac atrium	UBERON:0002081	86.15	gold quality
parietal pleura	UBERON:0002400	86.13	gold quality
skeletal muscle tissue	UBERON:0001134	86.06	gold quality
renal medulla	UBERON:0000362	86.04	gold quality
calcaneal tendon	UBERON:0003701	85.95	gold quality
bronchial epithelial cell	CL:0002328	85.86	gold quality
medial globus pallidus	UBERON:0002477	85.81	gold quality
tendon	UBERON:0000043	85.78	gold quality
tongue	UBERON:0001723	85.49	gold quality
quadriceps femoris	UBERON:0001377	85.10	gold quality
epithelium of bronchus	UBERON:0002031	85.07	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.82

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

3 targets.

Target	Regulation
BECN1	Activation
NFE2L2	Activation
SIRT3	Activation

Upstream regulators (CollecTRI, top): BAG3

miRNA regulators (miRDB)

90 targeting SIRT5, 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-3613-3P	100.00	76.36	7965
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-23B-5P	99.98	66.07	587
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-6772-5P	99.94	67.01	577
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-106B-5P	99.88	74.72	2795

Literature-anchored findings (GeneRIF, showing 40)

• SIRT5 consists of eight exons and is found in two isoforms, which encode a 310 aa and a 299 aa protein, respectively. (PMID:16484774)
• Analyses did not yield convincing evidence for associations of schizophrenia with SIRT5. (PMID:16827919)
• Results describe the substrates and regulation mechanisms for the human mitochondrial sirtuins Sirt3 and Sirt5. (PMID:18680753)
• SIRT5 represents a risk factor for mitochondrial dysfunction-related diseases, including Parkinson’s, through accelerated molecular aging of disease-related genes. (PMID:20887790)
• these results indicate that human SIRT5 potentially controls various primate-specific functions via two isoforms with different intracellular localizations or stabilities. (PMID:21143562)
• we demonstrate that Sirt5, a member of the class III lysine deacetylases, can catalyze lysine demalonylation and lysine desuccinylation reactions both in vitro and in vivo (PMID:21908771)
• study found that Sirt5 is an efficient protein lysine desuccinylase and demalonylase in vitro; protein lysine succinylation may represent a posttranslational modification that can be reversed by Sirt5 in vivo (PMID:22076378)
• NAD(+)-dependent SIRT deacetylase has a role in regulating the expression of mitochondrial steroidogenic P450 (PMID:22585829)
• The bicyclic intermediate structure provides insights into the desuccinylation mechanism of human sirtuin 5 (SIRT5). (PMID:22767592)
• Analysis of Sirt5 structures and activity data suggest that an Arg/succinate interaction is the molecular basis of the differential nicotinamide sensitivities of the two Sirt5 activities. (PMID:23028781)
• Downregulation of SIRT5 is associated with head and neck squamous cell carcinoma. (PMID:23475622)
• Results suggest a role for SIRT5 in influencing oocyte quality and in vitro fertilization outcomes. (PMID:23978077)
• These results reveal a novel post-translational regulation of SOD1 by means of succinylation and SIRT5-dependent desuccinylation, which is important for the growth of lung tumor cells. (PMID:24140062)
• Expression of SIRT5 in the entorhinal cortex, hippocampus, and white matter increases during the progression of Alzheimer disease. It is seen in activated microglia. (PMID:24464653)
• SIRT1/SIRT5-mediated PML deacetylation plays a role in the regulation of cancer cell survival. (PMID:25032863)
• High SIRT5 expression facilitates cancer cell growth and drug resistance in non-small cell lung cancer. (PMID:25070488)
• The results reveal the Sirt5 substrate acyl selectivity and its molecular basis and enable the design of inhibitors for Sirt5. (PMID:25111069)
• Results show that mitochondrial sirtuins SIRT3, SIRT4, and SIRT5 can promote increased mitochondrial respiration and cellular metabolism and respond to excess glucose by inducing a coordinated increase of glycolysis and respiration. (PMID:25165814)
• This study demonstrated that SIRT15 downregulation in the liver of non-alcoholic fatty liver disease patients. (PMID:25361925)
• Data showed that SIRT5 was involved in protein post-translational modifications through its potent demalonylase, desuccinylase, and deglutarylase activities. Also, the protein was found in the mitochondrial, cytoplasmic, and nuclear compartments. [review] (PMID:25717114)
• Use of a pan-sirtuin inhibitor and shRNA-mediated protein knockdown led us to uncover a role for the NAD(+)-dependent family of sirtuins, and in particular for SIRT2 and SIRT5, in the regulation of the necroptotic cell death program (PMID:26001219)
• Data indicate that compared to non-neoplastic endometria (NNE), endometrial cancer (EC) showed SIRT7 mRNA overexpression, whereas SIRT1, SIRT2, SIRT4 and SIRT5 were underexpressed, and no significant differences were observed for SIRT3 and SIRT6. (PMID:26701732)
• mutual cooperation between Y102 and R105 residues in promoting the desuccinylation versus deacetylation reaction in SIRT5. (PMID:27023330)
• Our study uncovers a SIRT5-dependent mechanism that regulates cellular NADPH homeostasis and redox potential by promoting IDH2 desuccinylation and G6PD deglutarylation. (PMID:27113762)
• The function of the three mitochondrial sirtuins (SIRT3, SIRT4, SIRT5) and their role in disease are reviewed. (PMID:27164052)
• Results demonstrated presence of endogenous SIRT5 in mitochondria of cultured SH-EP cells, identified down-regulation of cellular oxidative stress by SIRT5 as one of the possible mechanisms mediating the anti-apoptotic effect of SIRT5 in SH-EP cells. (PMID:27577743)
• a side chain-to-side chain cyclic pentapeptide harboring a central N(epsilon)-carboxyethyl-thiocarbamoyl-lysine residue behaved as a strong and selective (versus human SIRT1/2/3/6) inhibitor against human SIRT5-catalyzed deacylation reaction. (PMID:27626398)
• Results show that SIRT5 binds to, desuccinylates and inhibits PKM2 activity. Increased levels of reactive oxygen species (ROS) decreases succinylation and activity of PKM2 by increasing its binding to SIRT5. Moreover, inhibition of SIRT5 suppresses tumor cell proliferation through desuccinylation of PKM2 K498. (PMID:28036303)
• Data (including data from studies using knockout mice) suggest that SIRT5 is targeted to protein complexes on the inner mitochondrial membrane via affinity for cardiolipin to promote respiratory chain function, particularly Complex I and Complex II; SIRT5 expression is observed in inner mitochondrial membrane of periportal hepatocytes. (PMID:28458255)
• In this study, we summarize biological functions of SIRT5 reported in normal tissues and in cancer and discuss potential mechanisms whereby SIRT5 may impact tumorigenesis, particularly focusing on its reported roles in metabolic reprogramming. Finally, we review current efforts to target SIRT5 pharmacologically (PMID:28707979)
• SIRT5 gene has an important regulatory role in liver carcinogenesis, and may function as a novel potential therapeutic target for HCC. (PMID:29115436)
• High SIRT5 expression is associated with Cancer Cell Proliferation. (PMID:29180469)
• This study showed that SIRT5 supports the anaplerotic entry of glutamine into the TCA cycle in malignant phenotypes of CRC via activating GLUD1. (PMID:29416026)
• Our study reveals a novel role of SIRT5 in inhibiting peroxisome-induced oxidative stress, in liver protection, and in suppressing hepatocellular carcinoma development. (PMID:29491006)
• Sirt5 inhibitors in combination with chemotherapeutic agents and/or cetuximab may represent a therapeutic strategy for colorectal cancer patients harboring wild-type Kras. (PMID:29514096)
• SIRT5 plays pivotal roles in cardiac physiology and stress responses and is involved in the regulation of numerous aspects of myocardial energy metabolism. SIRT5 is implicated in neoplasia, as both a tumor promoter and suppressor in a context-specific manner, and may serve a protective function in the setting of neurodegenerative disorders. (PMID:29637793)
• The roles of the CDK2/SIRT5 axis in gastric cancer. (PMID:29896817)
• In human beings, SIRT5 gene encodes for four SIRT5 protein isoforms, namely SIRT5iso1, SIRT5iso2, SIRT5iso3, and SIRT5iso4. SIRT5(iso1-3) were mitochondria-localized, while SIRT5(iso4) localized mainly in cytoplasm. SIRT5(iso2-4) had little deacylase activity comparing with SIRT5(iso1). (PMID:29932920)
• The DNA variants and SNPs identified in acute Myocardial infection (AMI) patients may change SIRT5 level by affecting activity of SIRT5 gene promoter, contributing to the AMI development as a risk factor. (PMID:29981421)
• miR-299-3p suppresses migration, invasion and proliferation of Hepatocellular carcinoma cells via directly targeting SIRT5 (PMID:30170358)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	sirt5	ENSDARG00000039684
mus_musculus	Sirt5	ENSMUSG00000054021
rattus_norvegicus	Sirt5	ENSRNOG00000017866

Paralogs (6): SIRT2 (ENSG00000068903), SIRT6 (ENSG00000077463), SIRT4 (ENSG00000089163), SIRT1 (ENSG00000096717), SIRT3 (ENSG00000142082), SIRT7 (ENSG00000187531)

Protein

Protein identifiers

NAD-dependent protein deacylase sirtuin-5, mitochondrial — Q9NXA8 (reviewed: Q9NXA8)

Alternative names: Regulatory protein SIR2 homolog 5, SIR2-like protein 5

All UniProt accessions (12): A0A7P0T877, A0A7P0T915, A0A7P0T9N1, A0A7P0T9X1, A0A7P0TA05, A0A7P0TBF5, A0A7P0Z490, A0A7P0Z4F6, A0A7P0Z4N6, Q9NXA8, Q7Z3A0, U3KQT8

UniProt curated annotations — full annotation on UniProt →

Function. NAD-dependent lysine demalonylase, desuccinylase and deglutarylase that specifically removes malonyl, succinyl and glutaryl groups on target proteins. Activates CPS1 and contributes to the regulation of blood ammonia levels during prolonged fasting: acts by mediating desuccinylation and deglutarylation of CPS1, thereby increasing CPS1 activity in response to elevated NAD levels during fasting. Activates SOD1 by mediating its desuccinylation, leading to reduced reactive oxygen species. Activates SHMT2 by mediating its desuccinylation. Modulates ketogenesis through the desuccinylation and activation of HMGCS2. Has weak NAD-dependent protein deacetylase activity; however this activity may not be physiologically relevant in vivo. Can deacetylate cytochrome c (CYCS) and a number of other proteins in vitro such as UOX.

Subunit / interactions. Interacts with CPS1. Interacts with PCCA. Monomer. Homodimer. Forms homodimers upon suramin binding.

Subcellular location. Mitochondrion matrix. Mitochondrion intermembrane space. Cytoplasm. Cytosol. Nucleus Cytoplasm. Mitochondrion Mitochondrion.

Tissue specificity. Widely expressed.

Activity regulation. Inhibited by suramin. NAD-dependent lysine desuccinylase activity is inhibited by physiological nicotinamide concentrations, while deacetylase activity is not. In contrast, resveratrol activates deacetylase activity, while inhibiting desuccinylase activity.

Cofactor. Binds 1 zinc ion per subunit.

Domain organisation. In contrast to class I sirtuins, class III sirtuins have only weak deacetylase activity. Difference in substrate specificity is probably due to a larger hydrophobic pocket with 2 residues (Tyr-102 and Arg-105) that bind to malonylated and succinylated substrates and define the specificity.

Miscellaneous. The mechanism of demalonylation and desuccinylation involves the presence of a 1’,2’-cyclic intermediate, suggesting that sirtuins use the ADP-ribose-peptidylamidate mechanism to remove acyl groups from substrate lysine residues.

Similarity. Belongs to the sirtuin family. Class III subfamily.

Isoforms (4)

UniProt ID	Names	Canonical?
Q9NXA8-1	1	yes
Q9NXA8-2	2
Q9NXA8-3	3
Q9NXA8-4	4

RefSeq proteins (22): NP_001180196, NP_001229756, NP_001363727, NP_001363728, NP_001363729, NP_001363730, NP_001363731, NP_001363732, NP_001363733, NP_001363734, NP_001363735, NP_001363736, NP_001363737, NP_001363738, NP_001363739, NP_001363740, NP_001363741, NP_001363742, NP_001363743, NP_001363744, NP_036373, NP_112534 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003000	Sirtuin	Family
IPR026590	Ssirtuin_cat_dom	Domain
IPR026591	Sirtuin_cat_small_dom_sf	Homologous_superfamily
IPR027546	Sirtuin_class_III	Family
IPR029035	DHS-like_NAD/FAD-binding_dom	Homologous_superfamily
IPR050134	NAD-dep_sirtuin_deacylases	Family

Pfam: PF02146

Enzyme classification (BRENDA):

• EC 2.3.1.B43 — (BRENDA: organisms, substrates, inhibitors, Km, kcat entries)

Catalyzed reactions (Rhea), 3 shown:

• N(6)-glutaryl-L-lysyl-[protein] + NAD(+) + H2O = 2’’-O-glutaryl-ADP-D-ribose + nicotinamide + L-lysyl-[protein] (RHEA:47664)
• N(6)-succinyl-L-lysyl-[protein] + NAD(+) + H2O = 2’’-O-succinyl-ADP-D-ribose + nicotinamide + L-lysyl-[protein] (RHEA:47668)
• N(6)-malonyl-L-lysyl-[protein] + NAD(+) + H2O = 2’’-O-malonyl-ADP-D-ribose + nicotinamide + L-lysyl-[protein] (RHEA:47672)

UniProt features (56 total): helix 15, strand 12, binding site 11, splice variant 4, mutagenesis site 4, turn 3, sequence variant 2, transit peptide 1, chain 1, domain 1, sequence conflict 1, active site 1

Structure

Experimental structures (PDB)

27 structures.

PDB	Method	Resolution (Å)
6EQS	X-RAY DIFFRACTION	1.32
6LJK	X-RAY DIFFRACTION	1.39
8Z54	X-RAY DIFFRACTION	1.45
5BWL	X-RAY DIFFRACTION	1.55
3RIY	X-RAY DIFFRACTION	1.55
7X3P	X-RAY DIFFRACTION	1.56
9V0H	X-RAY DIFFRACTION	1.67
4F56	X-RAY DIFFRACTION	1.7
6ACO	X-RAY DIFFRACTION	1.71
6LJM	X-RAY DIFFRACTION	1.78
6LJN	X-RAY DIFFRACTION	1.8
8Z56	X-RAY DIFFRACTION	1.81
8Z55	X-RAY DIFFRACTION	1.83
2B4Y	X-RAY DIFFRACTION	1.9
6ACL	X-RAY DIFFRACTION	1.92
4G1C	X-RAY DIFFRACTION	1.94
8Z57	X-RAY DIFFRACTION	1.96
6ACE	X-RAY DIFFRACTION	1.98
3RIG	X-RAY DIFFRACTION	2
4F4U	X-RAY DIFFRACTION	2
2NYR	X-RAY DIFFRACTION	2.06
5XHS	X-RAY DIFFRACTION	2.19
8GBL	X-RAY DIFFRACTION	2.24
6ACP	X-RAY DIFFRACTION	2.3
8Z58	X-RAY DIFFRACTION	2.4
4HDA	X-RAY DIFFRACTION	2.6
8GBN	X-RAY DIFFRACTION	2.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NXA8-F1	89.82	0.83

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): 158 (proton acceptor)

Ligand- & substrate-binding residues (11): 207; 212; 249–251; 275–277; 293; 58–77; 102; 105; 140–143; 166; 169

Mutagenesis-validated functional residues (4):

Position	Phenotype
69	abolishes enzyme activity.
102	increases the km for desuccinylation.
105	increases the km for desuccinylation. does not affect deacetylase activity.
158	abolishes desuccinylation and deglutarylation activity.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-2151201	Transcriptional activation of mitochondrial biogenesis
R-HSA-70635	Urea cycle
R-HSA-1592230	Mitochondrial biogenesis
R-HSA-1852241	Organelle biogenesis and maintenance

MSigDB gene sets: 126 (showing top): PID_HDAC_CLASSI_PATHWAY, GOBP_NEGATIVE_REGULATION_OF_REACTIVE_OXYGEN_SPECIES_METABOLIC_PROCESS, GOBP_MACROMOLECULE_DEACYLATION, GOBP_KETONE_METABOLIC_PROCESS, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_MUSCLE_CELL_APOPTOTIC_PROCESS, GOBP_PEPTIDYL_LYSINE_MODIFICATION, GOBP_RESPONSE_TO_ISCHEMIA, GOBP_REGULATION_OF_KETONE_METABOLIC_PROCESS, GOBP_REGULATION_OF_REACTIVE_OXYGEN_SPECIES_METABOLIC_PROCESS, GOCC_MITOCHONDRIAL_ENVELOPE, GOBP_KETONE_BIOSYNTHETIC_PROCESS, GOBP_CHROMATIN_REMODELING, GOBP_REACTIVE_OXYGEN_SPECIES_METABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_STRIATED_MUSCLE_CELL_APOPTOTIC_PROCESS

GO Biological Process (12): response to ischemia (GO:0002931), protein deacetylation (GO:0006476), mitochondrion organization (GO:0007005), regulation of ketone biosynthetic process (GO:0010566), negative regulation of cardiac muscle cell apoptotic process (GO:0010667), response to nutrient levels (GO:0031667), protein demalonylation (GO:0036046), peptidyl-lysine demalonylation (GO:0036047), protein desuccinylation (GO:0036048), peptidyl-lysine desuccinylation (GO:0036049), protein deglutarylation (GO:0061698), negative regulation of reactive oxygen species metabolic process (GO:2000378)

GO Molecular Function (10): zinc ion binding (GO:0008270), histone deacetylase activity, NAD-dependent (GO:0017136), NAD-dependent protein lysine deacetylase activity (GO:0034979), protein-malonyllysine demalonylase activity (GO:0036054), protein-succinyllysine desuccinylase activity (GO:0036055), protein-glutaryllysine deglutarylase activity (GO:0061697), NAD+ binding (GO:0070403), transferase activity (GO:0016740), acyltransferase activity, transferring groups other than amino-acyl groups (GO:0016747), metal ion binding (GO:0046872)

GO Cellular Component (7): nucleus (GO:0005634), mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), mitochondrial intermembrane space (GO:0005758), mitochondrial matrix (GO:0005759), cytosol (GO:0005829), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Mitochondrial biogenesis	1
Metabolism of amino acids and derivatives	1
Organelle biogenesis and maintenance	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein deacylation	4
NAD-dependent protein lysine deacylase activity	3
peptidyl-lysine modification	2
intracellular membrane-bounded organelle	2
cytoplasm	2
cellular anatomical structure	2
response to stress	1
organelle organization	1
regulation of biosynthetic process	1
regulation of ketone metabolic process	1
ketone biosynthetic process	1
regulation of small molecule metabolic process	1
cardiac muscle cell apoptotic process	1
negative regulation of striated muscle cell apoptotic process	1
regulation of cardiac muscle cell apoptotic process	1
response to stimulus	1
protein demalonylation	1
protein desuccinylation	1
negative regulation of metabolic process	1
reactive oxygen species metabolic process	1
regulation of reactive oxygen species metabolic process	1
transition metal ion binding	1
histone deacetylase activity	1
NAD-dependent protein lysine deacetylase activity	1
hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides	1
catalytic activity, acting on a protein	1
peptidyl-lysine desuccinylation	1
anion binding	1
NAD binding	1
catalytic activity	1
acyltransferase activity	1
cation binding	1
organelle inner membrane	1
mitochondrial membrane	1
mitochondrial envelope	1
organelle envelope lumen	1
mitochondrion	1
intracellular organelle lumen	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

2424 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SIRT5	CYCS	P00001	874
SIRT5	IDH2	P48735	738
SIRT5	SIRT4	Q9Y6E7	677
SIRT5	SIRT3	Q9NTG7	671
SIRT5	CPS1	P31327	636
SIRT5	HDAC11	Q96DB2	635
SIRT5	PPARGC1A	Q9UBK2	616
SIRT5	ACSS1	Q9NUB1	611
SIRT5	GLUD1	P00367	605
SIRT5	NDUFA9	Q16795	596
SIRT5	SIRT7	Q9NRC8	585
SIRT5	SIRT6	Q8N6T7	584
SIRT5	SIRT2	Q8IXJ6	582
SIRT5	HDAC10	Q969S8	571
SIRT5	F5H3C5	F5H3C5	568
SIRT5	SOD2	P04179	568

IntAct

51 interactions, top by confidence:

A	B	Type	Score
CWC15	CTNNBL1	psi-mi:“MI:0914”(association)	0.850
TAL1	TCF4	psi-mi:“MI:0914”(association)	0.690
rep	GLA	psi-mi:“MI:0914”(association)	0.530
HOXB5	VPS37C	psi-mi:“MI:0914”(association)	0.530
YBEY	NME4	psi-mi:“MI:0914”(association)	0.530
CPLX3	CIAO1	psi-mi:“MI:0914”(association)	0.530
ZSCAN18	ZNF24	psi-mi:“MI:0914”(association)	0.530
DMD	UTRN	psi-mi:“MI:0914”(association)	0.530
PARP12	GCLM	psi-mi:“MI:0914”(association)	0.530
TMEM184A	SLC33A1	psi-mi:“MI:0914”(association)	0.530
SIRT5	GLS	psi-mi:“MI:0403”(colocalization)	0.460
SIRT5	GLS	psi-mi:“MI:0915”(physical association)	0.460
SIRT5	HADHA	psi-mi:“MI:0915”(physical association)	0.400
CKAP2L	SIRT5	psi-mi:“MI:0915”(physical association)	0.400
SIRT5	SNCG	psi-mi:“MI:0915”(physical association)	0.400
MYC	SIRT5	psi-mi:“MI:0915”(physical association)	0.400
SGTB	ARHGAP32	psi-mi:“MI:0914”(association)	0.350
HNRNPD	ARHGAP32	psi-mi:“MI:0914”(association)	0.350
BAG6	CNOT1	psi-mi:“MI:0914”(association)	0.350
SORT1	SH3PXD2B	psi-mi:“MI:0914”(association)	0.350
Pik3r2	EDIL3	psi-mi:“MI:0914”(association)	0.350
ARHGAP27	MCRIP1	psi-mi:“MI:0914”(association)	0.350
rep	HERC2	psi-mi:“MI:0914”(association)	0.350
rep	PRDX5	psi-mi:“MI:0914”(association)	0.350
CAPZB	ENAH	psi-mi:“MI:0914”(association)	0.350
PCDH10	TMEM223	psi-mi:“MI:0914”(association)	0.350
MALSU1	VWA8	psi-mi:“MI:0914”(association)	0.350
HOXA4	RABGAP1L	psi-mi:“MI:0914”(association)	0.350
RABL3	GPR89A	psi-mi:“MI:0914”(association)	0.350

BioGRID (102): SIRT5 (Affinity Capture-MS), SIRT5 (Affinity Capture-MS), SIRT5 (Affinity Capture-MS), SIRT5 (Affinity Capture-MS), SIRT5 (Affinity Capture-MS), SIRT5 (Affinity Capture-MS), GLS (Affinity Capture-Western), SIRT5 (Affinity Capture-Western), SIRT5 (Affinity Capture-MS), SIRT5 (Affinity Capture-MS), SIRT5 (Affinity Capture-MS), SIRT5 (Affinity Capture-MS), SIRT5 (Affinity Capture-MS), SIRT5 (Affinity Capture-MS), SIRT5 (Affinity Capture-MS)

ESM2 similar proteins: A0A0J9UVG7, A0A250YGJ5, A0A2K5TU92, A0A559KX76, A8NWP2, C8V3W5, E1BRE2, E2RDZ6, E9GD30, F4P804, F7DKV7, F7EZ75, G5EB76, I1RN13, J4W6X9, O13492, P0CS88, P16081, P21334, P22945, P27783, P36842, P36858, P38681, P39863, P39869, P43100, P53686, P54898, P59941, Q3ZBQ0, Q57V41, Q59ST1, Q5AI90, Q5AW69, Q5HZN8, Q5R6G3, Q5RBF1, Q5RJQ4, Q68F47

Diamond homologs: A0A0J9UVG7, A0QC96, A0R2N3, A5U1J9, A8MBU4, A8NWP2, A9A0B2, A9SDL4, B4EVF5, C6A243, E1BRE2, E2RDZ6, E9GD30, F7D4X9, F7DKV7, F7EZ75, O07595, O25849, O28597, O30124, O58669, O67919, P0A2F2, P0A2F3, P53685, P66814, P75960, P9WGG2, P9WGG3, Q20480, Q3ZBQ0, Q4JBN2, Q4Q2Y6, Q4UZX0, Q584D5, Q5AI90, Q5HU51, Q5HZN8, Q5JG47, Q5L014

SIGNOR signaling

13 interactions.

A	Effect	B	Mechanism
BAG3	“down-regulates quantity by repression”	SIRT5	“transcriptional regulation”
SIRT5	“up-regulates quantity by expression”	BECN1	“transcriptional regulation”
SIRT5	“up-regulates activity”	GLS	binding
SIRT5	“up-regulates quantity by expression”	NFE2L2	“transcriptional regulation”
SIRT5	“up-regulates quantity by expression”	SIRT3	“transcriptional regulation”
SIRT5	“down-regulates activity”	ACOX1	“catalytic activity”
SIRT5	“up-regulates activity”	G6PD	“catalytic activity”
SIRT5	“up-regulates activity”	IDH2	“catalytic activity”
SIRT5	“up-regulates activity”	HMGCS2	“post translational modification”
SIRT5	“up-regulates activity”	CPS1	“post translational modification”
SIRT5	“up-regulates activity”	LDHB	deacetylation
SIRT5	“down-regulates activity”	SHMT2	“post translational modification”

Disease & clinical

Clinical variants and AI predictions

ClinVar

72 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	51
Likely benign	5
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2337 predictions. Top by Δscore:

Variant	Effect	Δscore
6:13579450:GTAA:G	acceptor_gain	1.0000
6:13584062:T:TA	acceptor_gain	1.0000
6:13584072:A:AG	acceptor_gain	1.0000
6:13584073:A:G	acceptor_gain	1.0000
6:13584074:A:AG	acceptor_gain	1.0000
6:13584075:G:GG	acceptor_gain	1.0000
6:13584226:G:GG	donor_gain	1.0000
6:13591894:GGT:G	donor_loss	1.0000
6:13591895:G:GA	donor_loss	1.0000
6:13591896:T:A	donor_loss	1.0000
6:13574685:G:GT	donor_gain	0.9900
6:13574697:G:GT	donor_gain	0.9900
6:13574788:G:GT	donor_gain	0.9900
6:13574789:G:T	donor_gain	0.9900
6:13579197:AGT:A	donor_gain	0.9900
6:13579449:A:AG	acceptor_gain	0.9900
6:13579450:G:GC	acceptor_gain	0.9900
6:13579450:GT:G	acceptor_gain	0.9900
6:13579450:GTA:G	acceptor_gain	0.9900
6:13584060:T:A	acceptor_gain	0.9900
6:13584071:TAAAG:T	acceptor_gain	0.9900
6:13584074:AGCCC:A	acceptor_gain	0.9900
6:13584075:GC:G	acceptor_gain	0.9900
6:13584075:GCC:G	acceptor_gain	0.9900
6:13584075:GCCC:G	acceptor_gain	0.9900
6:13584075:GCCCG:G	acceptor_gain	0.9900
6:13584221:TTC:T	donor_gain	0.9900
6:13584222:TCAAG:T	donor_loss	0.9900
6:13584224:AAG:A	donor_loss	0.9900
6:13584225:AGTAA:A	donor_loss	0.9900

AlphaMissense

1990 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:13599081:T:C	F223L	0.999
6:13599083:T:A	F223L	0.999
6:13599083:T:G	F223L	0.999
6:13588423:T:C	F70L	0.998
6:13588425:C:A	F70L	0.998
6:13588425:C:G	F70L	0.998
6:13591720:T:C	F101L	0.998
6:13591722:C:A	F101L	0.998
6:13591722:C:G	F101L	0.998
6:13591714:T:A	W99R	0.997
6:13591714:T:C	W99R	0.997
6:13588424:T:G	F70C	0.996
6:13588446:G:C	W77C	0.996
6:13588446:G:T	W77C	0.996
6:13591839:G:C	Q140H	0.996
6:13591839:G:T	Q140H	0.996
6:13599078:T:A	W222R	0.996
6:13599078:T:C	W222R	0.996
6:13599082:T:G	F223C	0.996
6:13600907:C:A	A272D	0.996
6:13591690:T:C	F91L	0.995
6:13591692:T:A	F91L	0.995
6:13591692:T:G	F91L	0.995
6:13591716:G:C	W99C	0.995
6:13591716:G:T	W99C	0.995
6:13591733:G:C	R105P	0.995
6:13591736:G:C	R106P	0.995
6:13599147:T:C	C245R	0.995
6:13588399:A:C	S62R	0.994
6:13588401:T:A	S62R	0.994

dbSNP variants (sampled 300 via entrez): RS1000075415 (6:13586661 T>C), RS1000174741 (6:13574612 C>G), RS1000181390 (6:13585559 A>G), RS1000194051 (6:13598881 G>A,C,T), RS1000211386 (6:13592096 C>T), RS1000213658 (6:13576165 A>G), RS1000282651 (6:13586946 G>A,T), RS1000314500 (6:13582671 G>T), RS1000363584 (6:13605050 T>C), RS1000425158 (6:13601358 T>G), RS1000535704 (6:13607052 C>T), RS1000770458 (6:13575749 A>G), RS1000892964 (6:13588290 C>A), RS1000928597 (6:13611564 T>G), RS1000950711 (6:13581573 T>A)

Disease associations

OMIM: gene MIM:604483 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST008766_2	Perceived intensity of sweet substances	9.000000e-06
GCST90011899_37	Aspartate aminotransferase levels	4.000000e-18

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004736	aspartate aminotransferase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2163183 (SINGLE PROTEIN), CHEMBL4742324 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

9 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 426,071 (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
CHEMBL1201346	BALSALAZIDE	4	8,319
CHEMBL1358	FULVESTRANT	4	56,655
CHEMBL1541	CEFIXIME	4	27,787
CHEMBL249837	METHACYCLINE	4	13,102
CHEMBL608	PROBUCOL	4	30,435
CHEMBL265502	SURAMIN	3	36,848
CHEMBL12131	CLOSANTEL	2	7,051
CHEMBL46469	ANTHRALIN	2	14,186

PharmGKB: 1 entry (VIP=true, CPIC=false)

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 (1 total), top 1:

Ligand	Action	Affinity	Parameter
compound 2 [Maurer et al., 2012]	Inhibition	5.64	pIC50

Binding affinities (BindingDB)

10 measured of 11 human assays (11 total across all organisms); most potent 10 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
CHEMBL5199270	KI	0.5 nM
CHEMBL5209031	KI	7 nM
CHEMBL5185695	IC50	290 nM
phenyl N-[1-anilino-6-(heptanethioylamino)-1-oxohexan-2-yl]carbamate	IC50	310 nM	US-9359293: Methods of treatment using modulators of SIRT2
CHEMBL5188575	IC50	370 nM
CHEMBL5172115	IC50	830 nM
CHEMBL5171330	IC50	900 nM
phenyl N-[1-anilino-6-(butanethioylamino)-1-oxohexan-2-yl]carbamate	IC50	2400 nM	US-9359293: Methods of treatment using modulators of SIRT2
CHEMBL5201503	IC50	5100 nM
phenyl N-[1-anilino-6-(ethanethioylamino)-1-oxohexan-2-yl]carbamate	IC50	30000 nM	US-9359293: Methods of treatment using modulators of SIRT2

ChEMBL bioactivities

414 potent at pChembl≥5 of 711 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
11.00	Kd	0.01	nM	CHEMBL4091790
9.92	Kd	0.12	nM	CHEMBL4064460
9.30	Ki	0.5	nM	CHEMBL5199270
8.46	Ki	3.5	nM	CHEMBL4068735
8.46	Ki	3.5	nM	CHEMBL4092751
8.46	Ki	3.5	nM	CHEMBL4065067
8.46	Ki	3.5	nM	CHEMBL4100475
8.46	Ki	3.5	nM	CHEMBL4073655
8.22	Ki	6	nM	CHEMBL4636862
8.15	Ki	7	nM	CHEMBL4091258
8.15	Ki	7	nM	CHEMBL5209031
7.87	Ki	13.6	nM	CHEMBL4064460
7.81	IC50	15.4	nM	CHEMBL4091258
7.72	IC50	19.1	nM	CHEMBL4064460
7.66	Ki	22	nM	CHEMBL5172115
7.64	Ki	23	nM	CHEMBL4100351
7.52	IC50	30.3	nM	CHEMBL4091790
7.52	IC50	30	nM	CHEMBL4091790
7.43	Ki	37	nM	CHEMBL5188575
7.35	Ki	45	nM	CHEMBL6114923
7.34	IC50	45.9	nM	CHEMBL4100351
7.34	IC50	46.1	nM	CHEMBL4065953
7.23	IC50	59	nM	CHEMBL4083471
7.08	Ki	83.2	nM	CHEMBL4085990
7.07	IC50	86.1	nM	CHEMBL4084850
7.05	IC50	89.9	nM	CHEMBL4101463
7.04	IC50	91.1	nM	CHEMBL4085990
7.02	IC50	95	nM	CHEMBL4079616
7.00	IC50	100	nM	ANTHRALIN
6.99	IC50	101.9	nM	CHEMBL4078223
6.96	IC50	110	nM	CHEMBL4636862
6.96	IC50	110	nM	CHEMBL5177283
6.92	IC50	119.9	nM	CHEMBL4097208
6.89	Ki	129	nM	CHEMBL6160490
6.87	Ki	135	nM	CHEMBL4079212
6.82	IC50	150	nM	CHEMBL6160490
6.75	IC50	176.6	nM	CHEMBL4092610
6.68	IC50	207	nM	CHEMBL4063400
6.68	IC50	210	nM	CHEMBL5398650
6.64	IC50	230	nM	CHEMBL5177283
6.62	IC50	240	nM	CHEMBL5398650
6.60	IC50	250	nM	CHEMBL5398650
6.58	Ki	263	nM	CHEMBL4068365
6.58	IC50	260	nM	CHEMBL5197912
6.58	IC50	260	nM	CHEMBL5398650
6.58	IC50	260	nM	CHEMBL6133053
6.56	IC50	273.5	nM	CHEMBL4079212
6.55	IC50	280	nM	CHEMBL6109002
6.54	IC50	290	nM	CHEMBL5185695
6.53	IC50	295.1	nM	CHEMBL4093875

PubChem BioAssay actives

370 with measured affinity, of 1075 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
(4S)-5-[[(2S)-1-[[2-[[(2S)-1-amino-3-methyl-1-oxobutan-2-yl]amino]-2-oxoethyl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[(2-benzamidoacetyl)amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-6-[[(3S)-3-carboxy-3-naphthalen-2-ylsulfanylpropanoyl]amino]hexanoyl]amino]-5-oxopentanoic acid	1455616: Binding affinity to human N-terminal biotinylated SIRT5 by surface plasmon resonance spectroscopy	kd	<0.0001	uM
(4S)-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[4-[3-[2-[2-[3-[5-[(3aS,4S,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]propoxy]ethoxy]ethoxy]propylamino]-4-oxobutanoyl]amino]acetyl]amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-6-[[(3S)-3-carboxy-3-naphthalen-2-ylsulfanylpropanoyl]amino]hexanoyl]amino]-5-[[(2S)-1-[[2-[[(2S)-1-amino-3-methyl-1-oxobutan-2-yl]amino]-2-oxoethyl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-5-oxopentanoic acid	1455616: Binding affinity to human N-terminal biotinylated SIRT5 by surface plasmon resonance spectroscopy	kd	0.0001	uM
(2S)-N-[(2S)-1-(cyclobutylamino)-3-(1H-indol-3-yl)-1-oxopropan-2-yl]-2-[(3-fluorophenyl)sulfonylamino]-6-[2-(2H-tetrazol-5-yl)ethylcarbamothioylamino]hexanamide	1885222: Binding affinity to SIRT5 (unknown origin) assessed as deglutarylase activity by measuring inhibition constant	ki	0.0005	uM
(4S)-5-[[(2S)-1-[[2-[[(2S)-1-amino-3-methyl-1-oxobutan-2-yl]amino]-2-oxoethyl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[(2-benzamidoacetyl)amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-6-[[3-carboxy-3-(2-pyrazin-2-ylethylsulfanyl)propanoyl]amino]hexanoyl]amino]-5-oxopentanoic acid	1455609: Inhibition of human recombinant N-terminal Strep2-tagged SIRT5 expressed in Escherichia coli BL21 (DE3) using Abz-GVLK(glutaryl)AY(NO2)GV-NH2 as substrate in presence of NAD+ by fluorescence assay	ki	0.0035	uM
(4S)-5-[[(2S)-1-[[2-[[(2S)-1-amino-3-methyl-1-oxobutan-2-yl]amino]-2-oxoethyl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[(2-benzamidoacetyl)amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-6-[[3-carboxy-3-(2-pyridin-2-ylethylsulfanyl)propanoyl]amino]hexanoyl]amino]-5-oxopentanoic acid	1455609: Inhibition of human recombinant N-terminal Strep2-tagged SIRT5 expressed in Escherichia coli BL21 (DE3) using Abz-GVLK(glutaryl)AY(NO2)GV-NH2 as substrate in presence of NAD+ by fluorescence assay	ki	0.0035	uM
(4S)-5-[[(2S)-1-[[2-[[(2S)-1-amino-3-methyl-1-oxobutan-2-yl]amino]-2-oxoethyl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[(2-benzamidoacetyl)amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-6-[[(3S)-3-carboxy-3-[2-(3,5-dimethyl-1,2-oxazol-4-yl)ethylsulfanyl]propanoyl]amino]hexanoyl]amino]-5-oxopentanoic acid	1455609: Inhibition of human recombinant N-terminal Strep2-tagged SIRT5 expressed in Escherichia coli BL21 (DE3) using Abz-GVLK(glutaryl)AY(NO2)GV-NH2 as substrate in presence of NAD+ by fluorescence assay	ki	0.0035	uM
(4S)-5-[[(2S)-1-[[2-[[(2S)-1-amino-3-methyl-1-oxobutan-2-yl]amino]-2-oxoethyl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[(2-benzamidoacetyl)amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-6-[[3-carboxy-3-(2-pyridin-4-ylethylsulfanyl)propanoyl]amino]hexanoyl]amino]-5-oxopentanoic acid	1455609: Inhibition of human recombinant N-terminal Strep2-tagged SIRT5 expressed in Escherichia coli BL21 (DE3) using Abz-GVLK(glutaryl)AY(NO2)GV-NH2 as substrate in presence of NAD+ by fluorescence assay	ki	0.0035	uM
(4S)-5-[[(2S)-1-[[2-[[(2S)-1-amino-3-methyl-1-oxobutan-2-yl]amino]-2-oxoethyl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[(2-benzamidoacetyl)amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-6-[[(3R)-3-carboxy-3-[2-(3,5-dimethyl-1,2-oxazol-4-yl)ethylsulfanyl]propanoyl]amino]hexanoyl]amino]-5-oxopentanoic acid	1455609: Inhibition of human recombinant N-terminal Strep2-tagged SIRT5 expressed in Escherichia coli BL21 (DE3) using Abz-GVLK(glutaryl)AY(NO2)GV-NH2 as substrate in presence of NAD+ by fluorescence assay	ki	0.0035	uM
3-[[(5S)-6-[[(2S)-1-(cyclobutylamino)-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-5-[(3-fluorophenyl)sulfonylamino]-6-oxohexyl]carbamothioylamino]propanoic acid	1885222: Binding affinity to SIRT5 (unknown origin) assessed as deglutarylase activity by measuring inhibition constant	ki	0.0060	uM
(4S)-5-[[(2S)-1-[[2-[[(2S)-1-amino-3-methyl-1-oxobutan-2-yl]amino]-2-oxoethyl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[(2-benzamidoacetyl)amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-6-[[(3S)-3-carboxy-3-(naphthalen-1-ylmethylsulfanyl)propanoyl]amino]hexanoyl]amino]-5-oxopentanoic acid	1455609: Inhibition of human recombinant N-terminal Strep2-tagged SIRT5 expressed in Escherichia coli BL21 (DE3) using Abz-GVLK(glutaryl)AY(NO2)GV-NH2 as substrate in presence of NAD+ by fluorescence assay	ki	0.0070	uM
(2S)-N-[(2S)-1-(cyclobutylamino)-3-(1H-indol-3-yl)-1-oxopropan-2-yl]-2-[(3-fluorophenyl)sulfonylamino]-6-[2-(5-oxo-4H-1,2,4-oxadiazol-3-yl)ethylcarbamothioylamino]hexanamide	1885222: Binding affinity to SIRT5 (unknown origin) assessed as deglutarylase activity by measuring inhibition constant	ki	0.0070	uM
5-[[(5S)-6-[[(2S)-3-(1H-indol-3-yl)-1-oxo-1-(propan-2-ylamino)propan-2-yl]amino]-6-oxo-5-(phenylmethoxycarbonylamino)hexyl]amino]-5-sulfanylidenepentanoic acid	1885222: Binding affinity to SIRT5 (unknown origin) assessed as deglutarylase activity by measuring inhibition constant	ki	0.0220	uM
(4S)-5-[[(2S)-1-[[2-[[(2S)-1-amino-3-methyl-1-oxobutan-2-yl]amino]-2-oxoethyl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[(2-benzamidoacetyl)amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-6-[[(3S)-3-carboxy-3-(3,4-dichlorophenyl)sulfanylpropanoyl]amino]hexanoyl]amino]-5-oxopentanoic acid	1455609: Inhibition of human recombinant N-terminal Strep2-tagged SIRT5 expressed in Escherichia coli BL21 (DE3) using Abz-GVLK(glutaryl)AY(NO2)GV-NH2 as substrate in presence of NAD+ by fluorescence assay	ki	0.0230	uM
3-[[(5S)-6-[[(2S)-3-(1H-indol-3-yl)-1-oxo-1-(propan-2-ylamino)propan-2-yl]amino]-6-oxo-5-(phenylmethoxycarbonylamino)hexyl]carbamothioylamino]propanoic acid	1885222: Binding affinity to SIRT5 (unknown origin) assessed as deglutarylase activity by measuring inhibition constant	ki	0.0370	uM
(4S)-5-[[(2S)-1-[[2-[[(2S)-1-amino-3-methyl-1-oxobutan-2-yl]amino]-2-oxoethyl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[(2-benzamidoacetyl)amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-6-[[(3S)-3-carboxy-3-(3,4-dimethylphenyl)sulfanylpropanoyl]amino]hexanoyl]amino]-5-oxopentanoic acid	1455609: Inhibition of human recombinant N-terminal Strep2-tagged SIRT5 expressed in Escherichia coli BL21 (DE3) using Abz-GVLK(glutaryl)AY(NO2)GV-NH2 as substrate in presence of NAD+ by fluorescence assay	ic50	0.0461	uM
(2S)-4-[[(5S)-6-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-amino-3-methyl-1-oxobutan-2-yl]amino]-2-oxoethyl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-5-[[(2S)-2-[[(2S)-2-[(2-benzamidoacetyl)amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-6-oxohexyl]amino]-2-methyl-2-naphthalen-1-ylsulfanyl-4-oxobutanoic acid	1455609: Inhibition of human recombinant N-terminal Strep2-tagged SIRT5 expressed in Escherichia coli BL21 (DE3) using Abz-GVLK(glutaryl)AY(NO2)GV-NH2 as substrate in presence of NAD+ by fluorescence assay	ic50	0.0590	uM
(4S)-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[4-[3-[2-[2-[3-[5-[(3aS,4S,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]propoxy]ethoxy]ethoxy]propylamino]-4-oxobutanoyl]amino]acetyl]amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-6-[(3-carboxy-3-naphthalen-2-ylsulfanylpropanoyl)amino]hexanoyl]amino]-5-[[(2S)-1-[[2-[[(2S)-1-amino-3-methyl-1-oxobutan-2-yl]amino]-2-oxoethyl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-5-oxopentanoic acid	1455621: Competitive inhibition of human recombinant N-terminal Strep2-tagged SIRT5 expressed in Escherichia coli BL21 (DE3) using Abz-GVLK(glutaryl)AY(NO2)GV-NH2 as substrate in presence of NAD+ by fluorescence assay	ki	0.0832	uM
(4S)-5-[[(2S)-1-[[2-[[(2S)-1-amino-3-methyl-1-oxobutan-2-yl]amino]-2-oxoethyl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[(2-benzamidoacetyl)amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-6-[[(3S)-3-carboxy-3-(3,5-dichlorophenyl)sulfanylpropanoyl]amino]hexanoyl]amino]-5-oxopentanoic acid	1455609: Inhibition of human recombinant N-terminal Strep2-tagged SIRT5 expressed in Escherichia coli BL21 (DE3) using Abz-GVLK(glutaryl)AY(NO2)GV-NH2 as substrate in presence of NAD+ by fluorescence assay	ic50	0.0861	uM
(2R)-4-[[(5S)-6-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-amino-3-methyl-1-oxobutan-2-yl]amino]-2-oxoethyl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-5-[[(2S)-2-[[(2S)-2-[(2-benzamidoacetyl)amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-6-oxohexyl]amino]-2-methyl-2-naphthalen-1-ylsulfanyl-4-oxobutanoic acid	1455609: Inhibition of human recombinant N-terminal Strep2-tagged SIRT5 expressed in Escherichia coli BL21 (DE3) using Abz-GVLK(glutaryl)AY(NO2)GV-NH2 as substrate in presence of NAD+ by fluorescence assay	ic50	0.0899	uM
(4S)-5-[[(2S)-1-[[2-[[(2S)-1-amino-3-methyl-1-oxobutan-2-yl]amino]-2-oxoethyl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[(2-benzamidoacetyl)amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-6-[[(3S)-3-carboxy-3-naphthalen-1-ylsulfanylpropanoyl]amino]hexanoyl]amino]-5-oxopentanoic acid	1455609: Inhibition of human recombinant N-terminal Strep2-tagged SIRT5 expressed in Escherichia coli BL21 (DE3) using Abz-GVLK(glutaryl)AY(NO2)GV-NH2 as substrate in presence of NAD+ by fluorescence assay	ic50	0.0950	uM
Anthralin	1455622: Inhibition of SIRT5 (unknown origin) using GGQSLK[succ]FGKG as substrate after 30 mins	ic50	0.1000	uM
(4S)-5-[[(2S)-1-[[2-[[(2S)-1-amino-3-methyl-1-oxobutan-2-yl]amino]-2-oxoethyl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[(2-benzamidoacetyl)amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-6-[[(3S)-3-carboxy-3-(4-chlorophenyl)sulfanylpropanoyl]amino]hexanoyl]amino]-5-oxopentanoic acid	1455609: Inhibition of human recombinant N-terminal Strep2-tagged SIRT5 expressed in Escherichia coli BL21 (DE3) using Abz-GVLK(glutaryl)AY(NO2)GV-NH2 as substrate in presence of NAD+ by fluorescence assay	ic50	0.1019	uM
3-[[(5S)-6-[[(2S)-1-(cyclopentylamino)-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-5-[(3-fluorophenyl)sulfonylamino]-6-oxohexyl]carbamothioylamino]propanoic acid	1873015: Inhibition of SIRT5 (unknown origin)	ic50	0.1100	uM
(4S)-5-[[(2S)-1-[[2-[[(2S)-1-amino-3-methyl-1-oxobutan-2-yl]amino]-2-oxoethyl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[(2-benzamidoacetyl)amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-6-[[(3S)-3-carboxy-3-(3-chlorophenyl)sulfanylpropanoyl]amino]hexanoyl]amino]-5-oxopentanoic acid	1455609: Inhibition of human recombinant N-terminal Strep2-tagged SIRT5 expressed in Escherichia coli BL21 (DE3) using Abz-GVLK(glutaryl)AY(NO2)GV-NH2 as substrate in presence of NAD+ by fluorescence assay	ic50	0.1199	uM
(4S)-5-[[(2S)-1-[[2-[[(2S)-1-amino-3-methyl-1-oxobutan-2-yl]amino]-2-oxoethyl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[(2-benzamidoacetyl)amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-6-[[(3S)-3-carboxy-3-phenylsulfanylpropanoyl]amino]hexanoyl]amino]-5-oxopentanoic acid	1455609: Inhibition of human recombinant N-terminal Strep2-tagged SIRT5 expressed in Escherichia coli BL21 (DE3) using Abz-GVLK(glutaryl)AY(NO2)GV-NH2 as substrate in presence of NAD+ by fluorescence assay	ki	0.1350	uM
(4S)-5-[[(2S)-1-[[2-[[(2S)-1-amino-3-methyl-1-oxobutan-2-yl]amino]-2-oxoethyl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[(2-benzamidoacetyl)amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-6-[[(3S)-3-carboxy-3-(2,4-dichlorophenyl)sulfanylpropanoyl]amino]hexanoyl]amino]-5-oxopentanoic acid	1455609: Inhibition of human recombinant N-terminal Strep2-tagged SIRT5 expressed in Escherichia coli BL21 (DE3) using Abz-GVLK(glutaryl)AY(NO2)GV-NH2 as substrate in presence of NAD+ by fluorescence assay	ic50	0.1766	uM
(4S)-5-[[(2S)-1-[[2-[[(2S)-1-amino-3-methyl-1-oxobutan-2-yl]amino]-2-oxoethyl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[(2-benzamidoacetyl)amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-6-[[(3R)-3-carboxy-3-(naphthalen-1-ylmethylsulfanyl)propanoyl]amino]hexanoyl]amino]-5-oxopentanoic acid	1455609: Inhibition of human recombinant N-terminal Strep2-tagged SIRT5 expressed in Escherichia coli BL21 (DE3) using Abz-GVLK(glutaryl)AY(NO2)GV-NH2 as substrate in presence of NAD+ by fluorescence assay	ic50	0.2070	uM
4-[(E)-[1-[4-(4-chlorophenyl)-1,3-thiazol-2-yl]-3-methyl-5-oxopyrazol-4-ylidene]methyl]benzoic acid	2007544: Inhibition of human SIRT5 by fluorescence based analysis	ic50	0.2100	uM
3-[[(5S)-6-[[(2S)-1-(cyclopropylamino)-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-5-[(3-fluorophenyl)sulfonylamino]-6-oxohexyl]carbamothioylamino]propanoic acid	1885221: Inhibition of SIRT5 deglutarylase activity (unknown origin)	ic50	0.2600	uM
(4S)-5-[[(2S)-1-[[2-[[(2S)-1-amino-3-methyl-1-oxobutan-2-yl]amino]-2-oxoethyl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[(2-benzamidoacetyl)amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-6-[(3-carboxy-4-phenylbutanoyl)amino]hexanoyl]amino]-5-oxopentanoic acid	1455609: Inhibition of human recombinant N-terminal Strep2-tagged SIRT5 expressed in Escherichia coli BL21 (DE3) using Abz-GVLK(glutaryl)AY(NO2)GV-NH2 as substrate in presence of NAD+ by fluorescence assay	ki	0.2630	uM
(2S)-N-[(2S)-1-(cyclobutylamino)-3-(1H-indol-3-yl)-1-oxopropan-2-yl]-2-[(3-fluorophenyl)sulfonylamino]-6-[2-(5-oxo-2H-1,2-oxazol-3-yl)ethylcarbamothioylamino]hexanamide	1885221: Inhibition of SIRT5 deglutarylase activity (unknown origin)	ic50	0.2900	uM
(4S)-5-[[(2S)-1-[[2-[[(2S)-1-amino-3-methyl-1-oxobutan-2-yl]amino]-2-oxoethyl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[(2-benzamidoacetyl)amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-6-[[(3S)-3-carboxy-3-(2,5-dichlorophenyl)sulfanylpropanoyl]amino]hexanoyl]amino]-5-oxopentanoic acid	1455609: Inhibition of human recombinant N-terminal Strep2-tagged SIRT5 expressed in Escherichia coli BL21 (DE3) using Abz-GVLK(glutaryl)AY(NO2)GV-NH2 as substrate in presence of NAD+ by fluorescence assay	ic50	0.2951	uM
3-[3-[[2-(2-chloroanilino)-5-[(3R)-3-phenylpyrrolidine-1-carbonyl]pyrimidin-4-yl]amino]propylcarbamothioylamino]propanoic acid	2010903: Inhibition of human SIRT5 (34 to 269 residues) using Ac-Leu-Gly-Ser-Lys (Su)-AMC as fluorogenic substrate in presence of NAD+	ic50	0.3097	uM
(4S)-5-[[(2S)-1-[[2-[[(2S)-1-amino-3-methyl-1-oxobutan-2-yl]amino]-2-oxoethyl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[(2-benzamidoacetyl)amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-6-[[(3S)-3-carboxy-3-(3,4-dimethoxyphenyl)sulfanylpropanoyl]amino]hexanoyl]amino]-5-oxopentanoic acid	1455609: Inhibition of human recombinant N-terminal Strep2-tagged SIRT5 expressed in Escherichia coli BL21 (DE3) using Abz-GVLK(glutaryl)AY(NO2)GV-NH2 as substrate in presence of NAD+ by fluorescence assay	ic50	0.3258	uM
(4S)-5-[[(2S)-1-[[2-[[(2S)-1-amino-3-methyl-1-oxobutan-2-yl]amino]-2-oxoethyl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[(2-benzamidoacetyl)amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-6-[[(3S)-3-benzylsulfanyl-3-carboxypropanoyl]amino]hexanoyl]amino]-5-oxopentanoic acid	1455609: Inhibition of human recombinant N-terminal Strep2-tagged SIRT5 expressed in Escherichia coli BL21 (DE3) using Abz-GVLK(glutaryl)AY(NO2)GV-NH2 as substrate in presence of NAD+ by fluorescence assay	ic50	0.3357	uM
3-[[(5S)-6-(3-hydroxyanilino)-5-[[(2S)-4-methyl-2-(phenylmethoxycarbonylamino)pentanoyl]amino]-6-oxohexyl]carbamothioylamino]propanoic acid	1885220: Inhibition of SIRT5 desuccinylase activity (unknown origin)	ic50	0.3400	uM
(2S)-4-[[(5S)-5-[[(2S)-2-acetamido-4-methylpentanoyl]amino]-6-[[(2S)-1-amino-1-oxopropan-2-yl]amino]-6-oxohexyl]amino]-2-naphthalen-2-ylsulfanyl-4-oxobutanoic acid	1455609: Inhibition of human recombinant N-terminal Strep2-tagged SIRT5 expressed in Escherichia coli BL21 (DE3) using Abz-GVLK(glutaryl)AY(NO2)GV-NH2 as substrate in presence of NAD+ by fluorescence assay	ic50	0.3504	uM
(4S)-5-[[(2S)-1-[[2-[[(2S)-1-amino-3-methyl-1-oxobutan-2-yl]amino]-2-oxoethyl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[(2-benzamidoacetyl)amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-6-[[(3R)-3-carboxy-3-[(2-chlorophenyl)methylsulfanyl]propanoyl]amino]hexanoyl]amino]-5-oxopentanoic acid	1455609: Inhibition of human recombinant N-terminal Strep2-tagged SIRT5 expressed in Escherichia coli BL21 (DE3) using Abz-GVLK(glutaryl)AY(NO2)GV-NH2 as substrate in presence of NAD+ by fluorescence assay	ic50	0.3524	uM
8-[(2,6-dioxo-1,3-dipropyl-7H-purin-8-yl)disulfanyl]-1,3-dipropyl-7H-purine-2,6-dione	1873015: Inhibition of SIRT5 (unknown origin)	ic50	0.3900	uM
8-[(1,3-diethyl-2,6-dioxo-7H-purin-8-yl)disulfanyl]-1,3-diethyl-7H-purine-2,6-dione	1873015: Inhibition of SIRT5 (unknown origin)	ic50	0.4200	uM
(4S)-5-[[(2S)-1-[[2-[[(2S)-1-amino-3-methyl-1-oxobutan-2-yl]amino]-2-oxoethyl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[(2-benzamidoacetyl)amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-6-[[(3R)-3-carboxy-3-[(2,4-dichlorophenyl)methylsulfanyl]propanoyl]amino]hexanoyl]amino]-5-oxopentanoic acid	1455609: Inhibition of human recombinant N-terminal Strep2-tagged SIRT5 expressed in Escherichia coli BL21 (DE3) using Abz-GVLK(glutaryl)AY(NO2)GV-NH2 as substrate in presence of NAD+ by fluorescence assay	ic50	0.4315	uM
3-[[6-(3,4-dihydro-2H-thiochromen-4-ylamino)-6-oxo-5-(phenylmethoxycarbonylamino)hexyl]carbamothioylamino]propanoic acid	1873014: Inhibition of GST-tagged SIRT5 (unknown origin) incubated for 10 mins by HPLC based analysis	ic50	0.4500	uM
3-ethyl-8-[[3-ethyl-2,6-dioxo-1-(2-phenylethyl)-7H-purin-8-yl]disulfanyl]-1-(2-phenylethyl)-7H-purine-2,6-dione	1873015: Inhibition of SIRT5 (unknown origin)	ic50	0.4500	uM
3-ethyl-8-[[3-ethyl-1-(oxan-4-ylmethyl)-2,6-dioxo-7H-purin-8-yl]disulfanyl]-1-(oxan-4-ylmethyl)-7H-purine-2,6-dione	1873015: Inhibition of SIRT5 (unknown origin)	ic50	0.5000	uM
4-[(E)-[3-methyl-5-oxo-1-[4-[4-(trifluoromethyl)phenyl]-1,3-thiazol-2-yl]pyrazol-4-ylidene]methyl]benzoic acid	2007544: Inhibition of human SIRT5 by fluorescence based analysis	ic50	0.5200	uM
3-[3-[[2-(2-chloroanilino)-5-(3-phenylpyrrolidine-1-carbonyl)pyrimidin-4-yl]amino]propylcarbamothioylamino]propanoic acid	2010903: Inhibition of human SIRT5 (34 to 269 residues) using Ac-Leu-Gly-Ser-Lys (Su)-AMC as fluorogenic substrate in presence of NAD+	ic50	0.5297	uM
(4S)-5-[[(2S)-1-[[2-[[(2S)-1-amino-3-methyl-1-oxobutan-2-yl]amino]-2-oxoethyl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[(2-benzamidoacetyl)amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-6-[[(3S)-3-carboxy-3-[(2-chlorophenyl)methylsulfanyl]propanoyl]amino]hexanoyl]amino]-5-oxopentanoic acid	1455609: Inhibition of human recombinant N-terminal Strep2-tagged SIRT5 expressed in Escherichia coli BL21 (DE3) using Abz-GVLK(glutaryl)AY(NO2)GV-NH2 as substrate in presence of NAD+ by fluorescence assay	ic50	0.5333	uM
(4S)-5-[[(2S)-1-[[2-[[(2S)-1-amino-3-methyl-1-oxobutan-2-yl]amino]-2-oxoethyl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[(2-benzamidoacetyl)amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-6-[[(3S)-3-carboxy-3-[(2,4-dichlorophenyl)methylsulfanyl]propanoyl]amino]hexanoyl]amino]-5-oxopentanoic acid	1455609: Inhibition of human recombinant N-terminal Strep2-tagged SIRT5 expressed in Escherichia coli BL21 (DE3) using Abz-GVLK(glutaryl)AY(NO2)GV-NH2 as substrate in presence of NAD+ by fluorescence assay	ic50	0.5433	uM
(4S)-5-[[(2S)-1-[[2-[[(2S)-1-amino-3-methyl-1-oxobutan-2-yl]amino]-2-oxoethyl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[(2-benzamidoacetyl)amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-6-[[(3S)-3-carboxy-3-(2,6-dichlorophenyl)sulfanylpropanoyl]amino]hexanoyl]amino]-5-oxopentanoic acid	1455609: Inhibition of human recombinant N-terminal Strep2-tagged SIRT5 expressed in Escherichia coli BL21 (DE3) using Abz-GVLK(glutaryl)AY(NO2)GV-NH2 as substrate in presence of NAD+ by fluorescence assay	ic50	0.5768	uM
3-[3-[[2-(2-chloroanilino)-5-[[(1R)-1-phenylpropyl]carbamoyl]pyrimidin-4-yl]amino]propylcarbamothioylamino]propanoic acid	2010903: Inhibition of human SIRT5 (34 to 269 residues) using Ac-Leu-Gly-Ser-Lys (Su)-AMC as fluorogenic substrate in presence of NAD+	ic50	0.5800	uM

CTD chemical–gene interactions

36 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, decreases methylation	3
Resveratrol	affects cotreatment, increases expression, affects reaction, decreases acetylation	2
Estradiol	affects expression, increases expression	2
GSK-J4	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
diisononyl phthalate	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
butyraldehyde	decreases expression	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
beta-methylcholine	affects expression	1
pentanal	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
N-(oxo-5,6-dihydrophenanthridin-2-yl)-N,N-dimethylacetamide hydrochloride	decreases reaction, increases expression	1
abrine	decreases expression	1
jinfukang	increases expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	affects binding, decreases reaction	1
Atrazine	decreases expression	1
Cisplatin	decreases response to substance, increases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Potassium Dichromate	increases expression	1
Silver	decreases expression	1
Smoke	decreases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1

ChEMBL screening assays

232 unique, capped per target: 232 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2166661	Binding	Activity of human SIRT5 assessed as decrotonylation of compound at 50 uM after 1 hr by trypsin developer-based fluorescence assay	Substrates for efficient fluorometric screening employing the NAD-dependent sirtuin 5 lysine deacylase (KDAC) enzyme. — J Med Chem

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B2FF	Abcam HeLa SIRT5 KO	Cancer cell line	Female
CVCL_B9RU	Abcam A-549 SIRT5 KO	Cancer cell line	Male
CVCL_TL34	HAP1 SIRT5 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.