TIPARP

Summary

TIPARP (TCDD inducible poly(ADP-ribose) polymerase, HGNC:23696) is a protein-coding gene on chromosome 3q25.31, encoding Protein mono-ADP-ribosyltransferase TIPARP (Q7Z3E1). ADP-ribosyltransferase that mediates mono-ADP-ribosylation of glutamate, aspartate and cysteine residues on target proteins. It is a selective cancer dependency (DepMap: 24.7% of cell lines).

This gene encodes a member of the poly(ADP-ribose) polymerase superfamily. Studies of the mouse ortholog have shown that the encoded protein catalyzes histone poly(ADP-ribosyl)ation and may be involved in T-cell function. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 25976 — RefSeq curated summary.

At a glance

• GWAS associations: 12
• Clinical variants (ClinVar): 84 total
• GTEx eGene: eQTL in 18 tissues, sQTL in 2 (q < 0.05)
• ChEMBL bioactivity: 4 clinical-phase molecules tested; no curated mechanism-of-action drug
• Cancer dependency (DepMap): dependent in 24.7% of screened cell lines
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.35 (highly constrained)
• MANE Select transcript: NM_015508
• Interaction hub: 3,848 STRING partners (top 1% of genes corpus-wide)
• Notable: 84 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23696
Approved symbol	TIPARP
Name	TCDD inducible poly(ADP-ribose) polymerase
Location	3q25.31
Locus type	gene with protein product
Status	Approved
Aliases	DKFZP434J214, DKFZp686N0351, DDF1, PARP7, PARP-7, PARP-1, pART14, RM1, ARTD14
Ensembl gene	ENSG00000163659
Ensembl biotype	protein_coding
OMIM	612480
Entrez	25976

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 9 protein_coding

MANE Select: ENST00000295924

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 5, TSL 2: 1, TSL 5: 1

ENST00000295924, ENST00000461166, ENST00000473702, ENST00000481853, ENST00000486483, ENST00000495891, ENST00000542783, ENST00000908901, ENST00001142542

RefSeq mRNA: 3 — MANE Select: NM_015508 NM_001184717, NM_001184718, NM_015508

CCDS: CCDS3177

Canonical transcript exons

ENST00000295924 — 6 exons

Exon	Start	End
ENSE00001076994	156703424	156703702
ENSE00001076995	156695865	156696025
ENSE00001076997	156694020	156694188
ENSE00001331334	156677657	156678614
ENSE00001331336	156674590	156674796
ENSE00004801109	156704684	156706770

Expression profiles

Bgee: expression breadth ubiquitous, 283 present calls, max score 99.58.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 61.7045 / max 1404.7012, expressed in 1820 samples.

Highest expression (Bgee): secondary oocyte, oocyte, upper leg skin, vena cava, cervix squamous epithelium.

Genetic regulation across tissues (GTEx eQTL / sQTL)

TIPARP is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 18 tissues and its splicing (sQTL) in 2 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

20 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Artery Tibial	eqtl	1.7e-10	+0.22	3:157076636:C:G
Nerve Tibial	eqtl	3.1e-09	-0.19	3:157134803:C:G
Muscle Skeletal	eqtl	3.1e-07	-0.16	3:157134803:C:G
Adipose Subcutaneous	eqtl	4.7e-05	-0.18	3:156970924:C:T
Thyroid	eqtl	2.0e-04	-0.21	3:156810842:T:C
Whole Blood	eqtl	2.6e-04	-0.14	3:156883018:G:C
Artery Aorta	eqtl	5.6e-04	+0.85	3:156769642:T:C
Cells Cultured fibroblasts	eqtl	7.9e-04	+0.19	3:156679960:C:T
Pancreas	eqtl	3.5e-03	-0.23	3:157137443:C:CCCTTTGG
Brain Frontal Cortex BA9	eqtl	5.3e-03	+0.33	3:155750979:C:G
Adipose Visceral Omentum	eqtl	7.6e-03	+0.11	3:157077679:A:G
Cells EBV-transformed lymphocytes	eqtl	1.0e-02	+0.67	3:155795962:T:A
Colon Sigmoid	eqtl	1.5e-02	-0.17	3:157065306:C:G
Lung	sqtl	2.5e-02	+1.12	3:156597809:T:G
Ovary	sqtl	3.4e-02	-1.93	3:157599991:C:T
Brain Cerebellum	eqtl	3.6e-02	+0.35	3:155867549:C:T
Esophagus Mucosa	eqtl	3.7e-02	-0.28	3:156718373:G:A
Bladder	eqtl	4.4e-02	+1.67	3:156073092:C:G
Adrenal Gland	eqtl	4.5e-02	-0.25	3:157197300:A:G
Esophagus Muscularis	eqtl	4.7e-02	+0.16	3:155757631:C:A

FANTOM5 promoters

4 alternative TSS:

Promoter ID	TPM avg	Samples expressed
39428	42.0909	1804
39427	18.5633	1799
39430	0.9524	440
39429	0.0979	22

Top tissues by expression

showing 100 of 292 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	99.58	gold quality
oocyte	CL:0000023	99.33	gold quality
upper leg skin	UBERON:0004262	97.83	gold quality
vena cava	UBERON:0004087	96.98	gold quality
cervix squamous epithelium	UBERON:0006922	96.47	gold quality
cauda epididymis	UBERON:0004360	96.46	gold quality
caput epididymis	UBERON:0004358	96.19	gold quality
calcaneal tendon	UBERON:0003701	95.97	gold quality
cervix epithelium	UBERON:0004801	95.97	gold quality
mucosa of urinary bladder	UBERON:0001259	95.71	gold quality
pharyngeal mucosa	UBERON:0000355	95.58	gold quality
urethra	UBERON:0000057	95.46	gold quality
palpebral conjunctiva	UBERON:0001812	95.27	gold quality
stromal cell of endometrium	CL:0002255	94.68	gold quality
esophagus squamous epithelium	UBERON:0006920	94.30	gold quality
left uterine tube	UBERON:0001303	93.92	gold quality
squamous epithelium	UBERON:0006914	93.92	gold quality
bronchial epithelial cell	CL:0002328	93.85	gold quality
tibia	UBERON:0000979	93.80	gold quality
cartilage tissue	UBERON:0002418	93.72	gold quality
pericardium	UBERON:0002407	93.71	gold quality
eye	UBERON:0000970	93.69	gold quality
epithelium of esophagus	UBERON:0001976	93.50	gold quality
nipple	UBERON:0002030	93.25	gold quality
heart right ventricle	UBERON:0002080	93.25	gold quality
skin of hip	UBERON:0001554	93.22	gold quality
mucosa of paranasal sinus	UBERON:0005030	92.86	gold quality
sperm	CL:0000019	92.85	gold quality
islet of Langerhans	UBERON:0000006	92.66	gold quality
penis	UBERON:0000989	92.37	gold quality
bronchus	UBERON:0002185	92.23	gold quality
lower lobe of lung	UBERON:0008949	92.17	gold quality
epithelium of bronchus	UBERON:0002031	92.14	gold quality
oral cavity	UBERON:0000167	91.78	gold quality
amniotic fluid	UBERON:0000173	91.72	gold quality
corpus epididymis	UBERON:0004359	91.62	gold quality
adult organism	UBERON:0007023	91.49	gold quality
choroid plexus epithelium	UBERON:0003911	91.48	gold quality
gall bladder	UBERON:0002110	91.36	gold quality
gingival epithelium	UBERON:0001949	91.35	gold quality
male germ cell	CL:0000015	91.34	gold quality
epithelial cell of pancreas	CL:0000083	91.29	gold quality
gingiva	UBERON:0001828	91.27	gold quality
epithelium of mammary gland	UBERON:0003244	91.21	gold quality
skin of abdomen	UBERON:0001416	91.01	gold quality
mammary duct	UBERON:0001765	90.92	gold quality
renal glomerulus	UBERON:0000074	90.82	gold quality
uterine cervix	UBERON:0000002	90.79	gold quality
seminal vesicle	UBERON:0000998	90.79	gold quality
metanephric glomerulus	UBERON:0004736	90.79	gold quality
superficial temporal artery	UBERON:0001614	90.49	gold quality
epithelium of nasopharynx	UBERON:0001951	90.43	gold quality
mammalian vulva	UBERON:0000997	90.38	gold quality
saphenous vein	UBERON:0007318	90.21	gold quality
zone of skin	UBERON:0000014	90.15	gold quality
parietal pleura	UBERON:0002400	90.13	gold quality
fallopian tube	UBERON:0003889	90.11	gold quality
pleura	UBERON:0000977	90.03	gold quality
trachea	UBERON:0003126	89.93	gold quality
peritoneum	UBERON:0002358	89.92	gold quality
omental fat pad	UBERON:0010414	89.90	gold quality
synovial joint	UBERON:0002217	89.86	gold quality
lower esophagus mucosa	UBERON:0035834	89.79	gold quality
ectocervix	UBERON:0012249	89.76	gold quality
left testis	UBERON:0004533	89.73	gold quality
decidua	UBERON:0002450	89.63	gold quality
adipose tissue of abdominal region	UBERON:0007808	89.62	gold quality
cardiac atrium	UBERON:0002081	89.55	gold quality
cranial nerve II	UBERON:0000941	89.49	gold quality
layer of synovial tissue	UBERON:0007616	89.43	gold quality
hindlimb stylopod muscle	UBERON:0004252	89.42	gold quality
testis	UBERON:0000473	89.39	gold quality
right atrium auricular region	UBERON:0006631	89.39	gold quality
myocardium	UBERON:0002349	89.38	gold quality
visceral pleura	UBERON:0002401	89.35	gold quality
right testis	UBERON:0004534	89.33	gold quality
skin of leg	UBERON:0001511	89.31	gold quality
tibial artery	UBERON:0007610	89.20	gold quality
popliteal artery	UBERON:0002250	89.18	gold quality
smooth muscle tissue	UBERON:0001135	89.05	gold quality
pigmented layer of retina	UBERON:0001782	88.94	gold quality
left ovary	UBERON:0002119	88.94	gold quality
retina	UBERON:0000966	88.92	gold quality
right ovary	UBERON:0002118	88.88	gold quality
esophagus mucosa	UBERON:0002469	88.80	gold quality
cardiac muscle of right atrium	UBERON:0003379	88.78	gold quality
corpus callosum	UBERON:0002336	88.68	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.64	gold quality
mammary gland	UBERON:0001911	88.60	gold quality
tibial nerve	UBERON:0001323	88.55	gold quality
thoracic mammary gland	UBERON:0005200	88.53	gold quality
lung	UBERON:0002048	88.52	gold quality
nephron tubule	UBERON:0001231	88.40	gold quality
kidney epithelium	UBERON:0004819	88.37	gold quality
urinary bladder	UBERON:0001255	88.36	gold quality
oviduct epithelium	UBERON:0004804	88.25	gold quality
left ventricle myocardium	UBERON:0006566	88.09	silver quality
bone marrow	UBERON:0002371	87.92	gold quality
trigeminal ganglion	UBERON:0001675	87.85	gold quality
ovary	UBERON:0000992	87.83	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-CURD-46	yes	16.11
E-MTAB-9467	yes	11.70
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 76 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Parathyroid gland	tissue	93.3
Bone marrow	tissue	69.9
Adipose tissue	tissue	63.1
Urinary bladder	tissue	60.5
Adrenal gland	tissue	53.4
Esophagus	tissue	51.8
Testis	tissue	47.0
Liver	tissue	41.4
Smooth muscle	tissue	40.8
Breast	tissue	37.2
Fallopian tube	tissue	30.3
Spinal cord	tissue	30.2
Endometrium 1	tissue	28.6
Cervix	tissue	27.9
Pancreas	tissue	27.9
Seminal vesicle	tissue	26.2
Gallbladder	tissue	26.2
Kidney	tissue	26.2
Ovary	tissue	25.9
Lung	tissue	25.8
Prostate	tissue	24.2
Vagina	tissue	23.9
Nucleus accumbens	tissue	23.8
Small intestine	tissue	21.7
Postcentral gyrus	tissue	21.7
Hippocampus	tissue	21.6
Stomach 1	tissue	20.7
Choroid plexus	tissue	20.4
Thymus	tissue	20.2
Cerebellum	tissue	19.8
Locus coeruleus	tissue	19.3
Putamen	tissue	18.8
Corpus callosum	tissue	18.4
Olfactory bulb	tissue	18.1
Basal ganglia	tissue	18.0
Skin 1	tissue	17.8
Septum	tissue	17.3
Tonsil	tissue	17.0
Retina	tissue	16.9
Medulla oblongata	tissue	16.8
Ventral forebrain	tissue	16.8
Midbrain	tissue	16.2
Hypothalamus	tissue	15.9
Thyroid gland	tissue	15.9
Superior colliculi	tissue	15.7
Substantia nigra	tissue	15.7
Periaqueductal gray	tissue	15.7
Amygdala	tissue	15.3
Thalamus	tissue	15.2
Hippocampal formation	tissue	15.1
Appendix	tissue	15.1
Heart muscle	tissue	14.8
Cerebral cortex	tissue	14.8
Retrosplenial cortex	tissue	14.8
Pituitary gland	tissue	14.6
Entorhinal cortex	tissue	14.6
Motor cortex	tissue	14.5
Pons	tissue	14.4
Colon	tissue	14.2
Prefrontal cortex	tissue	13.9

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Nucleus raphe pallidus (60.2), Area postrema (51.0), Median raphe nucleus (46.6), Anterior thalamic nucleus, ventral (44.4), Peritrigeminal nucleus (40.0).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting TIPARP by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 117 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777
HSA-MIR-302C-3P	99.89	71.20	1778
HSA-MIR-302D-3P	99.89	71.25	1777
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-373-3P	99.84	70.68	1668
HSA-MIR-520E-3P	99.84	70.55	1698
HSA-MIR-372-3P	99.83	70.58	1691
HSA-MIR-520A-3P	99.83	70.59	1687

Functional genomics

gnomAD constraint: pLI 1, LOEUF 0.346, missense Z 2.73 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000295924 splits into 4 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
3:156,677,698–156,678,412	261 / 279.2	0.93	no
3:156,678,413–156,678,506	14 / 37.6	0.37	no
3:156,678,507–156,704,730	252 / 303.9	0.83	no
3:156,704,731–156,705,128	77 / 161.0	0.48	no
DepMap (CRISPR cell-line fitness): dependent in 24.7% of screened cell lines.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): JOPACA-1 (-2.002), LCLC-97TM1 (-1.834), JHH-6 (-1.684), MG-63 (-1.676), OV7 (-1.517), MM1-S (-1.511), BICR 22 (-1.5), Shmac 4 (-1.499), Hs 683 (-1.464), LO68 (-1.464), UM-RC-7 (-1.458), NCI-H650 (-1.457), Panc 04.03 (-1.441), TGBC1TKB (-1.438), KKU-100 (-1.411).

Literature-anchored findings (GeneRIF, showing 20)

• TIPARP (DKFZp434J214) gene is amplified in HNSCC. TIPARP, FLJ22693 and ZAP proteins with TPH, WW and PARP-like domains constitute the TIPARP family. (PMID:12851707)
• Single nucleotide polymorphism in TIPARP is associated with ovarian cancer. (PMID:20852632)
• Knockdown of TiPARP, but not AHRR, increased 2,3,7,8-tetrachlorodibenzo-p-dioxin - induced CYP1A1 mRNA and AHR protein levels. (PMID:24806346)
• these data identify a new mechanism of LXR regulation that involves TIPARP, ADP-ribosylation and MACROD1. (PMID:26814197)
• TIPARP is a viral RNA-sensing pattern recognition receptors that mediates antiviral responses triggered by BAX- and BAK1-dependent mitochondrial damage (PMID:28213497)
• Moreover, time course and promoter activity assays suggest that TIPARP and TIPARP-AS1 work in concert to regulate AHR signaling. Collectively, these data show an added level of complexity in the AHR signaling cascade which involves lncRNAs, whose functions remain poorly understood. (PMID:29274782)
• circHECTD1 functions as an endogenous MIR142 (microRNA 142) sponge to inhibit MIR142 activity, resulting in the inhibition of TIPARP (TCDD inducible poly[ADP-ribose] polymerase) expression with subsequent inhibition of astrocyte activation via macroautophagy/autophagy. (PMID:29938598)
• Mutation of cysteine 39 to alanine resulted in a small, but significant, reduction in TCDD inducible poly(ADP-ribose) polymerase protein (TIPARP) autoribosylation activity. (PMID:30373764)
• TiPARP forms nuclear condensates to degrade HIF-1alpha and suppress tumorigenesis. (PMID:32482854)
• Chemical genetics and proteome-wide site mapping reveal cysteine MARylation by PARP-7 on immune-relevant protein targets. (PMID:33475084)
• Identification of PARP-7 substrates reveals a role for MARylation in microtubule control in ovarian cancer cells. (PMID:33475085)
• Post-Transcriptional Regulation of PARP7 Protein Stability Is Controlled by Androgen Signaling. (PMID:33572475)
• PARP7 and Mono-ADP-Ribosylation Negatively Regulate Estrogen Receptor alpha Signaling in Human Breast Cancer Cells. (PMID:33799807)
• Androgen signaling uses a writer and a reader of ADP-ribosylation to regulate protein complex assembly. (PMID:33976187)
• PARP7 mono-ADP-ribosylates the agonist conformation of the androgen receptor in the nucleus. (PMID:34264286)
• PARP7 negatively regulates the type I interferon response in cancer cells and its inhibition triggers antitumor immunity. (PMID:34375612)
• TIPARP is involved in the regulation of intraocular pressure. (PMID:36536086)
• Induction of PARP7 Creates a Vulnerability for Growth Inhibition by RBN2397 in Prostate Cancer Cells. (PMID:37077937)
• Transcriptome screening identifies TIPARP as an antiviral host factor against the Getah virus. (PMID:37768084)
• PARP7-mediated ADP-ribosylation of FRA1 promotes cancer cell growth by repressing IRF1- and IRF3-dependent apoptosis. (PMID:38011562)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	tiparp	ENSDARG00000061841
mus_musculus	Tiparp	ENSMUSG00000034640
rattus_norvegicus	Tiparp	ENSRNOG00000011238

Paralogs (8): PARP12 (ENSG00000059378), ZC3HAV1 (ENSG00000105939), PARP11 (ENSG00000111224), PARP9 (ENSG00000138496), ZC3HAV1L (ENSG00000146858), PARP14 (ENSG00000173193), PARP15 (ENSG00000173200), PARP10 (ENSG00000178685)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:2159210) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 53 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal neurocranium morphology	1
short premaxilla	1
short maxilla	1
abnormal frontal bone morphology	1
abnormal sternum morphology	1
decreased hematocrit	1
short snout	1
enlarged liver	1
abnormal spleen morphology	1
enlarged spleen	1
abnormal smooth muscle morphology	1
scaly skin	1
anemia	1
abnormal blood vessel morphology	1
abnormal thymus involution	1
kidney inflammation	1
hemorrhage	1
reduced female fertility	1
decreased litter size	1
abnormal skin morphology	1
postnatal lethality	1
abnormal kidney morphology	1
long gestation period	1
hepatic steatosis	1
reticulocytosis	1

+28 more (showing top 25).

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
TIPARP-AS1	ncRNA	100287227
LEKR1	protein-coding	389170
SSR3	protein-coding	6747
LINC00886	ncRNA	730091
KCNAB1	protein-coding	7881
KCNAB1-AS2	ncRNA	100874083
KCNAB1-AS1	ncRNA	100874084

Protein

Protein identifiers

Protein mono-ADP-ribosyltransferase TIPARP — Q7Z3E1 (reviewed: Q7Z3E1)

Alternative names: ADP-ribosyltransferase diphtheria toxin-like 14, Poly [ADP-ribose] polymerase 7, TCDD-inducible poly [ADP-ribose] polymerase

All UniProt accessions (4): Q7Z3E1, C9JXM5, G5E9W1, H7C5K7

UniProt curated annotations — full annotation on UniProt →

Function. ADP-ribosyltransferase that mediates mono-ADP-ribosylation of glutamate, aspartate and cysteine residues on target proteins. Acts as a negative regulator of AHR by mediating mono-ADP-ribosylation of AHR, leading to inhibit transcription activator activity of AHR.

Subunit / interactions. Interacts with AHR.

Subcellular location. Nucleus.

Post-translational modifications. Auto-mono-ADP-ribosylated.

Activity regulation. ADP-ribosyltransferase activity is inhibited by PJ34; inhibition is however not specific to TIPARP and other PARP-domain containing proteins are also inhibited by PJ34. Partially inhibited by KU0058948.

Similarity. Belongs to the ARTD/PARP family.

RefSeq proteins (3): NP_001171646, NP_001171647, NP_056323* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000571	Znf_CCCH	Domain
IPR004170	WWE_dom	Domain
IPR012317	Poly(ADP-ribose)pol_cat_dom	Domain
IPR037197	WWE_dom_sf	Homologous_superfamily
IPR051712	ARTD-AVP	Family

Pfam: PF00644

Enzyme classification (BRENDA)

• EC 2.4.2.30 — NAD+ ADP-ribosyltransferase (BRENDA: 32 organisms, 193 substrates, 306 inhibitors, 42 Km, 24 kcat entries)

Substrate kinetics (BRENDA)

5 substrates with measured Km, best-characterized 5. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
NAD+	0.002–0.251	25
(ADP-D-RIBOSYL)N-ACTIN	0.011–0.037	7
(ADP-D-RIBOSYL)N-SOYBEAN-TRYPSIN-INHIBITOR	0.03–0.429	6
(ADP-D-RIBOSYL)N-RHOA PROTEIN	0.017	1
N6-ETHENO-NAD+	0.0225	1

Catalyzed reactions (Rhea)

• L-aspartyl-[protein] + NAD(+) = 4-O-(ADP-D-ribosyl)-L-aspartyl-[protein] + nicotinamide (RHEA:54424)
• L-cysteinyl-[protein] + NAD(+) = S-(ADP-D-ribosyl)-L-cysteinyl-[protein] + nicotinamide + H(+) (RHEA:56612)
• L-glutamyl-[protein] + NAD(+) = 5-O-(ADP-D-ribosyl)-L-glutamyl-[protein] + nicotinamide (RHEA:58224)

UniProt features (18 total): mutagenesis site 6, sequence conflict 3, domain 2, chain 1, zinc finger region 1, region of interest 1, short sequence motif 1, compositionally biased region 1, modified residue 1, sequence variant 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7Z3E1-F1	70.00	0.43

Human Protein Atlas

Protein class: Metabolic proteins, Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): microtubules

Antibody reliability (HPA): IF approved

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1)

Type	Positions
Adp-ribosylcysteine	39

Mutagenesis-validated functional residues (6)

Position	Phenotype
41	partial relocalization to the cytoplasm.
243	relocalization to the cytosol.
532	abolishes adp-ribosyltransferase activity.
564	abolishes adp-ribosyltransferase activity.
631	does not affect adp-ribosyltransferase activity.
39	slight reduction of auto-mono-adp-ribosylation.

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

MSigDB gene sets: 363 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_DN, GOBP_PLATELET_DERIVED_GROWTH_FACTOR_RECEPTOR_SIGNALING_PATHWAY, GOBP_BODY_MORPHOGENESIS, GOBP_MUSCLE_TISSUE_DEVELOPMENT, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, AMIT_EGF_RESPONSE_60_HELA, TTTGTAG_MIR520D, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, MENSE_HYPOXIA_UP, GOBP_POSITIVE_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_REGULATION_OF_HORMONE_LEVELS, GTTAAAG_MIR302B, GENTILE_RESPONSE_CLUSTER_D3, CACCAGC_MIR138

GO Biological Process (4): negative regulation of gene expression (GO:0010629), positive regulation of protein catabolic process (GO:0045732), protein auto-ADP-ribosylation (GO:0070213), response to 2,3,7,8-tetrachlorodibenzodioxine (GO:1904612)

GO Molecular Function (11): cis-regulatory region sequence-specific DNA binding (GO:0000987), NAD+ poly-ADP-ribosyltransferase activity (GO:0003950), zinc ion binding (GO:0008270), nucleotidyltransferase activity (GO:0016779), NAD+-protein-cysteine ADP-ribosyltransferase activity (GO:0140803), NAD+-protein-aspartate ADP-ribosyltransferase activity (GO:0140806), NAD+-protein-glutamate ADP-ribosyltransferase activity (GO:0140807), NAD+-protein mono-ADP-ribosyltransferase activity (GO:1990404), transferase activity (GO:0016740), glycosyltransferase activity (GO:0016757), metal ion binding (GO:0046872)

GO Cellular Component (1): nucleus (GO:0005634)

GO top-level categories

19 GO namespaces:

Category	Terms
NAD+-protein mono-ADP-ribosyltransferase activity	3
pentosyltransferase activity	2
gene expression	1
regulation of gene expression	1
negative regulation of macromolecule biosynthetic process	1
positive regulation of catabolic process	1
protein catabolic process	1
regulation of protein catabolic process	1
positive regulation of protein metabolic process	1
post-translational protein modification	1
response to chemical	1
transcription cis-regulatory region binding	1
transition metal ion binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity, acting on a protein	1
catalytic activity	1
transferase activity	1
cation binding	1
intracellular membrane-bounded organelle	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 7 of 16 annotations. The rest are phylogenetic / computational / electronic (IEA).

7 experimentally-supported GO terms:

GO term	NS	Evidence
negative regulation of gene expression	BP	mutant phenotype
positive regulation of protein catabolic process	BP	mutant phenotype
nucleus	CC	direct assay
NAD+ poly-ADP-ribosyltransferase activity	MF	direct assay
NAD+-protein mono-ADP-ribosyltransferase activity	MF	direct assay
NAD+-protein-cysteine ADP-ribosyltransferase activity	MF	direct assay
cis-regulatory region sequence-specific DNA binding	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 3,848 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TIPARP	PARP1	P09874	842
TIPARP	PARP16	Q8N5Y8	602
TIPARP	AHR	P35869	601
TIPARP	CYP1B1	Q16678	584
TIPARP	CYP1A1	P04798	576
TIPARP	PARP6	Q2NL67	567
TIPARP	AHRR	A9YTQ3	565
TIPARP	PARP3	Q9Y6F1	550
TIPARP	PARP2	Q9UGN5	547
TIPARP	PARP8	Q8N3A8	547
TIPARP	PARP4	Q9UKK3	539
TIPARP	MACROD1	Q9BQ69	451
TIPARP	D6RE68	D6RE68	429
TIPARP	ZFAND5	O76080	423
TIPARP	ADPRS	Q9NX46	422

IntAct

Human interaction partners of TIPARP in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

3 partners by confidence:

Partner	Interaction type	MIscore	Records
RPL11	physical association	0.400	1
LAD1	association	0.350	1
XRN2	physical association	0.000	1

BioGRID (2,348 interactions; top human partners by supporting records in a sample of 600 records): CLPP (Affinity Capture-MS; 2 records), ABCB7 (Affinity Capture-MS), ABCD3 (Affinity Capture-MS), ABCE1 (Affinity Capture-MS), ABCF1 (Affinity Capture-MS), ABL2 (Affinity Capture-MS), ACADSB (Affinity Capture-MS), ACLY (Affinity Capture-MS), ACTB (Affinity Capture-MS), ACTL6A (Affinity Capture-MS), ADAR (Affinity Capture-MS), ADD1 (Affinity Capture-MS), ADD3 (Affinity Capture-MS), ADSL (Affinity Capture-MS), AGFG1 (Affinity Capture-MS)

Disease & clinical

Genetic variants

Variant evidence for TIPARP: 84 ClinVar records (0 pathogenic / likely pathogenic); 12 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	67
Likely benign	2
Benign	2

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 28 predictions of 533):

Position(s)	Effect	Δscore	Sites
3:156694007	acceptor_gain	1.0000
3:156694018–156694019	acceptor_loss	1.0000	6
3:156694189–156694190	donor_loss	1.0000	5
3:156695843	acceptor_gain	1.0000
3:156695848	acceptor_gain	1.0000
3:156695862	acceptor_gain	1.0000
3:156695863–156695864	acceptor_loss	1.0000	6
3:156703595	donor_gain	1.0000
3:156674797–156674798	donor_loss	0.9900	5
3:156695967	donor_gain	0.9900

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	8.84e-05
Breast Invasive Carcinoma (TCGA)	favorable	0.000363

Disease associations

OMIM: gene MIM:612480 | disease phenotypes:

GWAS associations

12 associations:

Study	Trait	p-value
GCST002748_4	Epithelial ovarian cancer	6e-51
GCST007656_21	Chronic obstructive pulmonary disease or resting heart rate (pleiotropy)	4e-11
GCST005667_20	Central corneal thickness	5e-11
GCST012490_595	Femur bone mineral density x serum urate levels interaction	2e-10
GCST010988_424	Adult body size	8e-10
GCST004713_16	Testicular germ cell tumor	7e-9
GCST011011_10	Youthful appearance (self-reported)	2e-8
GCST007576_366	Chronotype	6e-8
GCST003999_12	Nose size	2e-7
GCST000802_1	Ovarian cancer	3e-7
GCST010725_36	Malaria	1e-6
GCST010725_56	Malaria	6e-6

EFO canonical traits (from GWAS)

3 canonical traits:

EFO ID	Trait name
EFO:0005213	central corneal thickness
EFO:0008328	chronotype measurement
EFO:0004531	urate measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2380188 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 16,696 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

4 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL521686	OLAPARIB	4	13,785
CHEMBL4112930	PAMIPARIB	3	2,251
CHEMBL5095220	SARUPARIB	3	393
CHEMBL5095043	ATAMPARIB	1	267

PharmGKB: 1 entry (CPIC guideline: no)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Mono-ADP-ribosylating PARPs

Most potent curated ligand interactions (2 total), top 2:

Ligand	Action	Affinity	Parameter
atamparib	Inhibition	8.52	pIC50
(S)-XY-05	Inhibition	8.35	pIC50

Binding affinities (BindingDB)

794 measured of 1665 human assays (1665 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
CHEMBL5400567	IC50	0.11 nM
CHEMBL5397180	IC50	0.14 nM
CHEMBL5393845	IC50	0.179 nM
CHEMBL5422715	IC50	0.185 nM
CHEMBL5407242	IC50	0.188 nM
CHEMBL5421106	IC50	0.188 nM
(S)-1-(6-Oxo-5-(trifluoromethyl)-1,6-dihydropyridin-3-yl)propan-2-yl (S)-2-methyl-4-(5-(trifluoromethyl)pyrimidin-2-yl)piperazine-1-carboxylate	IC50	0.19 nM	US-20240351997: NOVEL PARP7 INHIBITOR AND USE THEREOF
2-(6-Oxo-5-(trifluoromethyl)-1,6-dihydropyridin-3-yl)ethyl 4-(5-cyclopentylpyrimidin-2-yl)piperazine-1-carboxylate	IC50	0.24 nM	US-20240351997: NOVEL PARP7 INHIBITOR AND USE THEREOF
CHEMBL5176874	IC50	0.25 nM
N-(1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)-5-(4-((7-ethyl-6-oxo-5,6-dihydro-1,5-naphthyridin-3-yl)methyl)piperazin-1-yl)picolinamide	IC50	0.32 nM	US-20250222116: PARP-1 DEGRADATION AGENT AND USE THEREOF
CHEMBL6165720	EC50	0.375 nM
(R)-(1-(6-Oxo-5-(trifluoromethyl)-1,6-dihydropyridin-3-yl)pyrrolidin-2-yl)methyl 4-(5-(trifluoromethyl)pyrimidin-2-yl)piperazine-1-carboxylate	IC50	0.38 nM	US-20240351997: NOVEL PARP7 INHIBITOR AND USE THEREOF
2-(6-Oxo-5-(trifluoromethyl)-1,6-dihydropyridin-3-yl)ethyl (R)-2-methyl-4-(5-(trifluoromethyl)pyrimidin-2-yl)piperazine-1-carboxylate	IC50	0.38 nM	US-20240351997: NOVEL PARP7 INHIBITOR AND USE THEREOF
2-(6-Oxo-5-(trifluoromethyl)-1,6-dihydropyridin-3-yl)ethyl 2-(methoxymethyl)-4-(5-(trifluoromethyl)pyrimidin-2-yl)piperazine-1-carboxylate	IC50	0.39 nM	US-20240351997: NOVEL PARP7 INHIBITOR AND USE THEREOF
CHEMBL5420649	IC50	0.4 nM
CHEMBL5568973	IC50	0.4 nM
5-[[(2S)-1-[3-[(11S)-5-chloro-8-oxa-1,3,13-triazatricyclo[9.4.0.02,7]pentadeca-2(7),3,5-trien-13-yl]-3-oxopropoxy]-3-methoxypropan-2-yl]amino]-4-(trifluoromethyl)diazinan-3-one	IC50	0.4 nM	US-20240336629: Tricyclic Derivatives Useful As PARP7 Inhibitors
(10S)-5-chloro-8-methyl-12-[3-[[(2S)-1-[6-oxo-5-(trifluoromethyl)diazinan-4-yl]azetidin-2-yl]methoxy]propanoyl]-1,3,8,12-tetrazatricyclo[8.4.0.02,7]tetradeca-2(7),3,5-trien-9-one	IC50	0.416 nM	US-20240336629: Tricyclic Derivatives Useful As PARP7 Inhibitors
CHEMBL6174091	EC50	0.42 nM
(10S)-5-bromo-8-methyl-12-[3-[(2S)-2-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-ylidene]amino]propoxy]propanoyl]-1,3,8,12-tetrazatricyclo[8.4.0.02,7]tetradeca-2(7),3,5-trien-9-one	IC50	0.424 nM	US-20240336629: Tricyclic Derivatives Useful As PARP7 Inhibitors
N-(2-(6-Oxo-5-(trifluoromethyl)-1,6-dihydropyridin-3-yl)ethyl)-4-(5-(trifluoromethyl)pyrimidin-2-yl)piperazine-1-carboxamide	IC50	0.44 nM	US-20240351997: NOVEL PARP7 INHIBITOR AND USE THEREOF
(10R)-5-chloro-8-methyl-12-[3-[[(2S)-1-[6-oxo-5-(trifluoromethyl)diazinan-4-yl]azetidin-2-yl]methoxy]propanoyl]-1,3,8,12-tetrazatricyclo[8.4.0.02,7]tetradeca-2(7),3,5-trien-9-one	IC50	0.446 nM	US-20240336629: Tricyclic Derivatives Useful As PARP7 Inhibitors
CHEMBL6145263	EC50	0.46 nM
2-(6-Oxo-5-(trifluoromethyl)-1,6-dihydropyridin-3-yl)ethyl 4-(5-(trifluoromethyl)pyridin-2-yl)piperazine-1-carboxylate	IC50	0.46 nM	US-20240351997: NOVEL PARP7 INHIBITOR AND USE THEREOF
2-(6-Oxo-5-(trifluoromethyl)-1,6-dihydropyridin-3-yl)ethyl (S)-3-ethyl-4-(5-(trifluoromethyl)pyrimidin-2-yl)piperazine-1-carboxylate	IC50	0.48 nM	US-20240351997: NOVEL PARP7 INHIBITOR AND USE THEREOF
2-(6-Oxo-5-(trifluoromethyl)-1,6-dihydropyridin-3-yl)ethyl 4-(5-(trifluoromethyl)pyrazin-2-yl)piperazine-1-carboxylate	IC50	0.49 nM	US-20240351997: NOVEL PARP7 INHIBITOR AND USE THEREOF
5-[(2S)-2-[[3-oxo-3-[5-(trifluoromethyl)-1,3,11-triazatricyclo[7.4.0.02,7]trideca-2,4,6,8-tetraen-11-yl]propoxy]methyl]azetidin-1-yl]-4-(trifluoromethyl)-4H-pyridazin-3-one	IC50	0.496 nM	US-20240336629: Tricyclic Derivatives Useful As PARP7 Inhibitors
(S)-1-(6-Oxo-5-(trifluoromethyl)-1,6-dihydropyridin-3-yl)propan-2-yl 4-(5-(methylcarbamoyl)pyrimidin-2-yl)piperazine-1-carboxylate	IC50	0.5 nM	US-20240351997: NOVEL PARP7 INHIBITOR AND USE THEREOF
(S)-1-(6-Oxo-5-(trifluoromethyl)-1,6-dihydropyridin-3-yl)propan-2-yl 4-(5-(difluoromethyl)pyrimidin-2-yl)piperazine-1-carboxylate	IC50	0.52 nM	US-20240351997: NOVEL PARP7 INHIBITOR AND USE THEREOF
(S)-1-(6-Oxo-5-(trifluoromethyl)-1,6-dihydropyridin-3-yl)propan-2-yl 4-(5-methylpyrimidin-2-yl)piperazine-1-carboxylate	IC50	0.52 nM	US-20240351997: NOVEL PARP7 INHIBITOR AND USE THEREOF
[(2S)-1-[6-oxo-5-(trifluoromethyl)-1H-pyridin-3-yl]propan-2-yl] 4-[5-(trifluoromethyl)pyrimidin-2-yl]piperazine-1-carboxylate	IC50	0.53 nM	US-20240351997: NOVEL PARP7 INHIBITOR AND USE THEREOF
2-(6-Oxo-5-(trifluoromethyl)-1,6-dihydropyridin-3-yl)ethyl (R)-3-(hydroxymethyl)-4-(5-(trifluoromethyl)pyrimidin-2-yl)piperazine-1-carboxylate	IC50	0.53 nM	US-20240351997: NOVEL PARP7 INHIBITOR AND USE THEREOF
2-(6-Oxo-5-(trifluoromethyl)-1,6-dihydropyridin-3-yl)ethyl 4-(5-(2-hydroxypropan-2-yl)pyrimidin-2-yl)piperazine-1-carboxylate	IC50	0.53 nM	US-20240351997: NOVEL PARP7 INHIBITOR AND USE THEREOF
2-(6-Oxo-5-(trifluoromethyl)-1,6-dihydropyridin-3-yl)ethyl (S)-2-ethyl-4-(5-(trifluoromethyl)pyrimidin-2-yl)piperazine-1-carboxylate	IC50	0.54 nM	US-20240351997: NOVEL PARP7 INHIBITOR AND USE THEREOF
(S)-1-(6-Oxo-5-(trifluoromethyl)-1,6-dihydropyridin-3-yl)propan-2-yl 4-(5-chloropyrimidin-2-yl)piperazine-1-carboxylate	IC50	0.56 nM	US-20240351997: NOVEL PARP7 INHIBITOR AND USE THEREOF
(S)-1-(6-Oxo-5-(trifluoromethyl)-1,6-dihydropyridin-3-yl)propan-2-yl 4-(5-(trifluoromethyl)pyridin-2-yl)piperidine-1-carboxylate	IC50	0.56 nM	US-20240351997: NOVEL PARP7 INHIBITOR AND USE THEREOF
5-[1-[(7-ethyl-6-oxo-8aH-1,5-naphthyridin-3-yl)methyl]-3,6-dihydro-2H-pyridin-4-yl]-N-methylpyridine-2-carboxamide	IC50	0.59 nM	US-20250034168: NITROGEN-CONTAINING HETEROCYCLIC DERIVATIVE PARP INHIBITOR AND USE THEREOF
(S)-1-(6-Oxo-5-(trifluoromethyl)-1,6-dihydropyridin-3-yl)propan-2-yl (2R,5S)-2,5-dimethyl-4-(5-(trifluoromethyl)pyrimidin-2-yl)piperazine-1-carboxylate	IC50	0.59 nM	US-20240351997: NOVEL PARP7 INHIBITOR AND USE THEREOF
5-[(2S)-2-[[3-[(11R)-5-chloro-8-oxa-1,3,13-triazatricyclo[9.4.0.02,7]pentadeca-2(7),3,5-trien-13-yl]-3-oxopropoxy]methyl]azetidin-1-yl]-4-(trifluoromethyl)diazinan-3-one	IC50	0.592 nM	US-20240336629: Tricyclic Derivatives Useful As PARP7 Inhibitors
[(2R)-2-(5-methyl-6-oxo-1H-pyridin-3-yl)propyl] 4-[5-(trifluoromethyl)pyrimidin-2-yl]piperazine-1-carboxylate	IC50	0.6 nM	US-20240351997: NOVEL PARP7 INHIBITOR AND USE THEREOF
(S)-1-(6-Oxo-5-(trifluoromethyl)-1,6-dihydropyridin-3-yl)propan-2-yl 4-(5-(trifluoromethyl)pyridin-2-yl)piperazine-1-carboxylate	IC50	0.6 nM	US-20240351997: NOVEL PARP7 INHIBITOR AND USE THEREOF
(S)-1-(6-Oxo-5-(trifluoromethyl)-1,6-dihydropyridin-3-yl)propan-2-yl 4-(5-(2-hydroxypropan-2-yl)pyrimidin-2-yl)piperazine-1-carboxylate	IC50	0.61 nM	US-20240351997: NOVEL PARP7 INHIBITOR AND USE THEREOF
2-(6-Oxo-5-(trifluoromethyl)-1,6-dihydropyridin-3-yl)ethyl (S)-3-(hydroxymethyl)-4-(5-(trifluoromethyl)pyrimidin-2-yl)piperazine-1-carboxylate	IC50	0.61 nM	US-20240351997: NOVEL PARP7 INHIBITOR AND USE THEREOF
3-(6-Oxo-5-(trifluoromethyl)-1,6-dihydropyridin-3-yl)phenyl (R)-3-(hydroxymethyl)-4-(5-(trifluoromethyl)pyrimidin-2-yl)piperazine-1-carboxylate	IC50	0.61 nM	US-20240351997: NOVEL PARP7 INHIBITOR AND USE THEREOF
(10S)-12-[3-[[(2S)-1-[1-[(4-methoxyphenyl)methyl]-6-oxo-5-(trifluoromethyl)pyridazin-4-yl]azetidin-2-yl]methoxy]propanoyl]-8-methyl-5-(trifluoromethyl)-1,3,8,12-tetrazatricyclo[8.4.0.02,7]tetradeca-2(7),3,5-trien-9-one	IC50	0.611 nM	US-20240336629: Tricyclic Derivatives Useful As PARP7 Inhibitors
CHEMBL5177385	IC50	0.611 nM
5-[[(2S)-1-[3-[(11R)-5-bromo-8-oxa-1,3,13-triazatricyclo[9.4.0.02,7]pentadeca-2(7),3,5-trien-13-yl]-3-oxopropoxy]propan-2-yl]amino]-4-(trifluoromethyl)diazinan-3-one	IC50	0.617 nM	US-20240336629: Tricyclic Derivatives Useful As PARP7 Inhibitors
CHEMBL6165111	EC50	0.62 nM
2-(6-Oxo-5-(trifluoromethyl)-1,6-dihydropyridin-3-yl)ethyl (R)-3-methyl-4-(5-(trifluoromethyl)pyrimidin-2-yl)piperazine-1-carboxylate	IC50	0.62 nM	US-20240351997: NOVEL PARP7 INHIBITOR AND USE THEREOF
(R)-1-Hydroxy-3-(6-oxo-5-(trifluoromethyl)-1,6-dihydropyridin-3-yl)propan-2-yl 4-(5-(trifluoromethyl)pyrimidin-2-yl)piperazine-1-carboxylate	IC50	0.62 nM	US-20240351997: NOVEL PARP7 INHIBITOR AND USE THEREOF

ChEMBL bioactivities

714 potent at pChembl≥5 of 718 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.96	IC50	0.11	nM	CHEMBL5400567
9.96	IC50	0.11	nM	CHEMBL5568745
9.85	IC50	0.141	nM	CHEMBL5394931
9.85	IC50	0.14	nM	CHEMBL5397180
9.82	IC50	0.151	nM	CHEMBL5413717
9.75	IC50	0.179	nM	CHEMBL5415829
9.75	IC50	0.179	nM	CHEMBL5393845
9.73	IC50	0.188	nM	CHEMBL5407242
9.73	IC50	0.188	nM	CHEMBL5421106
9.73	IC50	0.185	nM	CHEMBL5422715
9.68	IC50	0.21	nM	CHEMBL5403305
9.67	IC50	0.212	nM	CHEMBL5419793
9.66	Kd	0.22	nM	ATAMPARIB
9.63	IC50	0.233	nM	CHEMBL5409582
9.63	IC50	0.232	nM	CHEMBL5422627
9.58	IC50	0.263	nM	CHEMBL5425262
9.54	IC50	0.288	nM	CHEMBL5409458
9.43	EC50	0.375	nM	CHEMBL6165720
9.40	IC50	0.4	nM	CHEMBL5568973
9.40	IC50	0.4	nM	CHEMBL5572156
9.39	IC50	0.405	nM	CHEMBL5417113
9.38	EC50	0.42	nM	CHEMBL6174091
9.34	EC50	0.46	nM	CHEMBL6145263
9.25	IC50	0.56	nM	CHEMBL5639789
9.23	IC50	0.584	nM	CHEMBL5209116
9.21	IC50	0.6114	nM	CHEMBL5177385
9.21	EC50	0.62	nM	CHEMBL6165111
9.19	IC50	0.648	nM	CHEMBL5181016
9.18	IC50	0.66	nM	CHEMBL5647433
9.18	EC50	0.667	nM	CHEMBL6148942
9.17	IC50	0.671	nM	CHEMBL5407196
9.15	IC50	0.71	nM	CHEMBL5646537
9.11	EC50	0.786	nM	CHEMBL6143717
9.10	IC50	0.802	nM	CHEMBL5190796
9.09	IC50	0.806	nM	CHEMBL5183629
9.06	IC50	0.87	nM	CHEMBL5202833
9.05	IC50	0.9	nM	CHEMBL5569182
9.02	IC50	0.966	nM	CHEMBL5174619
9.01	IC50	0.97	nM	CHEMBL5647333
9.00	IC50	1.006	nM	CHEMBL5173659
8.93	IC50	1.173	nM	CHEMBL5180425
8.92	IC50	1.2	nM	CHEMBL5575932
8.91	IC50	1.243	nM	CHEMBL5183278
8.89	IC50	1.3	nM	CHEMBL5564709
8.89	IC50	1.3	nM	CHEMBL5565268
8.85	IC50	1.4	nM	CHEMBL5572070
8.77	IC50	1.7	nM	CHEMBL5592550
8.76	IC50	1.75	nM	CHEMBL5183278
8.73	IC50	1.86	nM	CHEMBL5646959
8.70	IC50	2	nM	CHEMBL5567069

PubChem BioAssay actives

140 with measured affinity, of 223 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
3-[[(3S)-3-hydroxy-4-oxo-4-[4-[5-(trifluoromethyl)pyrimidin-2-yl]piperazin-1-yl]butyl]amino]-5-(trifluoromethyl)-1H-pyridazin-6-one	2015542: Displacement of biotinylated RBN011147 probe from PARP7 (unknown origin) preincubated for 1 hr followed by probe addition and measured after 1.5 hrs by electrochemiluminescent assay	ic50	0.0001	uM
2-[7-fluoro-1-oxo-2-[(4S)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]isoquinolin-6-yl]-8H-pyrimido[5,4-b][1,4]oxazin-7-one	2038721: Displacement of biotinylated RBN011147 probe from PARP7 (unknown origin) preincubated for 1 hr followed by incubation with probe for 1.5 hrs by MSD electrochemiluminescent assay	ic50	0.0001	uM
6-[4-amino-5-(trifluoromethyl)pyrimidin-2-yl]-2-[(4R)-5-(difluoromethoxy)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]-7-fluoroisoquinolin-1-one	2038721: Displacement of biotinylated RBN011147 probe from PARP7 (unknown origin) preincubated for 1 hr followed by incubation with probe for 1.5 hrs by MSD electrochemiluminescent assay	ic50	0.0001	uM
4-[(2S)-2-[[3-[(11S)-5-chloro-8-oxa-1,3,13-triazatricyclo[9.4.0.02,7]pentadeca-2(7),3,5-trien-13-yl]-3-oxopropoxy]methyl]azetidin-1-yl]-5-(trifluoromethyl)-1H-pyridazin-6-one	2101350: Inhibition of PARP7 (unknown origin) incubated for 1 hr by chemiluminescence based microplate reader assay	ic50	0.0001	uM
4-[[(2S)-1-[3-oxo-3-[4-[5-(trifluoromethyl)pyrimidin-2-yl]piperazin-1-yl]propoxy]propan-2-yl]amino]-5-(trifluoromethyl)-1H-pyridazin-6-one	1869196: Binding affinity to PARP7 (unknown origin) assessed as dissociation constant	kd	0.0002	uM
3-[(2S)-2-[3-oxo-3-[4-[5-(trifluoromethyl)pyrimidin-2-yl]piperazin-1-yl]propyl]pyrrolidin-1-yl]-5-(trifluoromethyl)-1H-pyridazin-6-one	2015542: Displacement of biotinylated RBN011147 probe from PARP7 (unknown origin) preincubated for 1 hr followed by probe addition and measured after 1.5 hrs by electrochemiluminescent assay	ic50	0.0002	uM
3-[2-[3-oxo-3-[4-[5-(trifluoromethyl)pyrimidin-2-yl]piperazin-1-yl]propyl]-2,3-dihydroindol-1-yl]-5-(trifluoromethyl)-1H-pyridazin-6-one	2015542: Displacement of biotinylated RBN011147 probe from PARP7 (unknown origin) preincubated for 1 hr followed by probe addition and measured after 1.5 hrs by electrochemiluminescent assay	ic50	0.0002	uM
3-[methyl-[4-oxo-4-[4-[5-(trifluoromethyl)pyrimidin-2-yl]piperazin-1-yl]butyl]amino]-5-(trifluoromethyl)-1H-pyridazin-6-one	2015542: Displacement of biotinylated RBN011147 probe from PARP7 (unknown origin) preincubated for 1 hr followed by probe addition and measured after 1.5 hrs by electrochemiluminescent assay	ic50	0.0002	uM
3-[ethyl-[4-oxo-4-[4-[5-(trifluoromethyl)pyrimidin-2-yl]piperazin-1-yl]butyl]amino]-5-(trifluoromethyl)-1H-pyridazin-6-one	2015542: Displacement of biotinylated RBN011147 probe from PARP7 (unknown origin) preincubated for 1 hr followed by probe addition and measured after 1.5 hrs by electrochemiluminescent assay	ic50	0.0002	uM
3-(N-[4-oxo-4-[4-[5-(trifluoromethyl)pyrimidin-2-yl]piperazin-1-yl]butyl]anilino)-5-(trifluoromethyl)-1H-pyridazin-6-one	2015542: Displacement of biotinylated RBN011147 probe from PARP7 (unknown origin) preincubated for 1 hr followed by probe addition and measured after 1.5 hrs by electrochemiluminescent assay	ic50	0.0002	uM
1-[2-[7-fluoro-1-oxo-2-[(4S)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]isoquinolin-6-yl]-5-(trifluoromethyl)pyrimidin-4-yl]azetidine-3-carbonitrile	2038721: Displacement of biotinylated RBN011147 probe from PARP7 (unknown origin) preincubated for 1 hr followed by incubation with probe for 1.5 hrs by MSD electrochemiluminescent assay	ic50	0.0002	uM
7-fluoro-6-[4-[(2S,3R)-3-hydroxy-2-methylazetidin-1-yl]-5-(trifluoromethyl)pyrimidin-2-yl]-2-[(4S)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]isoquinolin-1-one	2038721: Displacement of biotinylated RBN011147 probe from PARP7 (unknown origin) preincubated for 1 hr followed by incubation with probe for 1.5 hrs by MSD electrochemiluminescent assay	ic50	0.0002	uM
sodium 1-[[4-fluoro-3-(3-oxo-4-pentan-3-ylpiperazine-1-carbonyl)phenyl]methyl]quinazolin-3-ide-2,4-dione	2019987: Inhibition of human recombinant N-terminal FLAG-tagged PARP7 (400 to 657(end) residues) expressed in Sf9 cells	ic50	0.0002	uM
6-(4-amino-5-chloropyrimidin-2-yl)-7-fluoro-2-[(4S)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]isoquinolin-1-one	2038721: Displacement of biotinylated RBN011147 probe from PARP7 (unknown origin) preincubated for 1 hr followed by incubation with probe for 1.5 hrs by MSD electrochemiluminescent assay	ic50	0.0002	uM
2-[(4R)-5-(difluoromethoxy)-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]pentyl]-6-[5-(difluoromethyl)pyrimidin-2-yl]-7-fluoroisoquinolin-1-one	2038721: Displacement of biotinylated RBN011147 probe from PARP7 (unknown origin) preincubated for 1 hr followed by incubation with probe for 1.5 hrs by MSD electrochemiluminescent assay	ic50	0.0002	uM
3-[[4-oxo-4-[4-[5-(trifluoromethyl)pyrimidin-2-yl]piperazin-1-yl]butyl]amino]-5-(trifluoromethyl)-1H-pyridazin-6-one	2015542: Displacement of biotinylated RBN011147 probe from PARP7 (unknown origin) preincubated for 1 hr followed by probe addition and measured after 1.5 hrs by electrochemiluminescent assay	ic50	0.0003	uM
3-[5-oxo-5-[4-[5-(trifluoromethyl)pyrimidin-2-yl]piperazin-1-yl]pentyl]-5-(trifluoromethyl)-1H-pyridazin-6-one	2015542: Displacement of biotinylated RBN011147 probe from PARP7 (unknown origin) preincubated for 1 hr followed by probe addition and measured after 1.5 hrs by electrochemiluminescent assay	ic50	0.0003	uM
5-(trifluoromethyl)-3-[[3-[4-[5-(trifluoromethyl)pyrimidin-2-yl]piperazine-1-carbonyl]phenyl]methyl]-1H-pyridazin-6-one	2015542: Displacement of biotinylated RBN011147 probe from PARP7 (unknown origin) preincubated for 1 hr followed by probe addition and measured after 1.5 hrs by electrochemiluminescent assay	ic50	0.0004	uM
6-[4-amino-5-(difluoromethyl)pyrimidin-2-yl]-4,7-difluoro-2-[(2S,4S)-2-fluoro-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]oxy]pentyl]isoquinolin-1-one	2241579: Inhibition of PARP7 in human NCI-H1373 cells assessed as increase in STAT1 phosphorylation at Tyr701 incubated for 48 hrs by LANCE Ultra sandwich assay	ec50	0.0004	uM
7,8-difluoro-2-[(2R,4S)-2-fluoro-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]oxy]pentyl]-6-(5-methoxypyrimidin-2-yl)isoquinolin-1-one	2241579: Inhibition of PARP7 in human NCI-H1373 cells assessed as increase in STAT1 phosphorylation at Tyr701 incubated for 48 hrs by LANCE Ultra sandwich assay	ec50	0.0004	uM
4-[(2S)-1-[3-[(11S)-5-chloro-8-oxa-1,3,13-triazatricyclo[9.4.0.02,7]pentadeca-2(7),3,5-trien-13-yl]-3-oxopropoxy]-3-methoxypropan-2-yl]oxy-5-(trifluoromethyl)-1H-pyridazin-6-one	2101350: Inhibition of PARP7 (unknown origin) incubated for 1 hr by chemiluminescence based microplate reader assay	ic50	0.0004	uM
4-[[(2S)-1-[3-[(11S)-5-chloro-8-oxa-1,3,13-triazatricyclo[9.4.0.02,7]pentadeca-2(7),3,5-trien-13-yl]-3-oxopropoxy]-3-methoxypropan-2-yl]amino]-5-(trifluoromethyl)-1H-pyridazin-6-one	2101350: Inhibition of PARP7 (unknown origin) incubated for 1 hr by chemiluminescence based microplate reader assay	ic50	0.0004	uM
6-[5-(difluoromethyl)pyrimidin-2-yl]-7,8-difluoro-2-[(2R,4S)-2-fluoro-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]oxy]pentyl]isoquinolin-1-one	2241579: Inhibition of PARP7 in human NCI-H1373 cells assessed as increase in STAT1 phosphorylation at Tyr701 incubated for 48 hrs by LANCE Ultra sandwich assay	ec50	0.0005	uM
12-[3-[(2S)-2-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]propoxy]propanoyl]-5-(trifluoromethyl)-1,3,8,12-tetrazatricyclo[8.4.0.02,7]tetradeca-2(7),3,5-trien-9-one	1875834: Inhibition of PARP7 (unknown origin) by HTRF assay	ic50	0.0006	uM
4-[(2S)-2-[[3-oxo-3-[(10S)-5-(trifluoromethyl)-8-oxa-1,3,12-triazatricyclo[8.4.0.02,7]tetradeca-2(7),3,5-trien-12-yl]propoxy]methyl]azetidin-1-yl]-5-(trifluoromethyl)-1H-pyridazin-6-one	2142430: Inhibition of PARP7 (unknown origin) using histone as substrate incubated for 1 hr by chemiluminescence assay	ic50	0.0006	uM
(10S)-8-methyl-12-[3-[[(2S)-1-[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]azetidin-2-yl]methoxy]propanoyl]-5-(trifluoromethyl)-1,3,8,12-tetrazatricyclo[8.4.0.02,7]tetradeca-2(7),3,5-trien-9-one	1875834: Inhibition of PARP7 (unknown origin) by HTRF assay	ic50	0.0006	uM
(10S)-8-ethenyl-12-[3-[(2S)-2-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]propoxy]propanoyl]-5-(trifluoromethyl)-1,3,8,12-tetrazatricyclo[8.4.0.02,7]tetradeca-2(7),3,5-trien-9-one	1875834: Inhibition of PARP7 (unknown origin) by HTRF assay	ic50	0.0006	uM
6-(5-chloropyrimidin-2-yl)-7,8-difluoro-2-[(2R,4S)-2-fluoro-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]oxy]pentyl]isoquinolin-1-one	2241579: Inhibition of PARP7 in human NCI-H1373 cells assessed as increase in STAT1 phosphorylation at Tyr701 incubated for 48 hrs by LANCE Ultra sandwich assay	ec50	0.0006	uM
3-[(2S)-2-[3-oxo-3-[4-[5-(trifluoromethyl)pyrimidin-2-yl]piperazin-1-yl]propyl]piperidin-1-yl]-5-(trifluoromethyl)-1H-pyridazin-6-one	2015542: Displacement of biotinylated RBN011147 probe from PARP7 (unknown origin) preincubated for 1 hr followed by probe addition and measured after 1.5 hrs by electrochemiluminescent assay	ic50	0.0007	uM
6-[5-(1,1-difluoroethyl)pyrimidin-2-yl]-7,8-difluoro-2-[(2R,4S)-2-fluoro-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]oxy]pentyl]isoquinolin-1-one	2241579: Inhibition of PARP7 in human NCI-H1373 cells assessed as increase in STAT1 phosphorylation at Tyr701 incubated for 48 hrs by LANCE Ultra sandwich assay	ec50	0.0007	uM
4-[2-[[3-oxo-3-[(10S)-5-(trifluoromethyl)-8-oxa-1,3,12-triazatricyclo[8.4.0.02,7]tetradeca-2(7),3,5-trien-12-yl]propoxy]methyl]azetidin-1-yl]-5-(trifluoromethyl)-1H-pyridazin-6-one	2142430: Inhibition of PARP7 (unknown origin) using histone as substrate incubated for 1 hr by chemiluminescence assay	ic50	0.0007	uM
4-[(2S)-2-[[3-[(10S)-5-chloro-8-oxa-1,3,12-triazatricyclo[8.4.0.02,7]tetradeca-2(7),3,5-trien-12-yl]-3-oxopropoxy]methyl]azetidin-1-yl]-5-(trifluoromethyl)-1H-pyridazin-6-one	2142430: Inhibition of PARP7 (unknown origin) using histone as substrate incubated for 1 hr by chemiluminescence assay	ic50	0.0007	uM
12-[3-[(2S)-2-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]oxy]propoxy]propanoyl]-8-(trideuteriomethyl)-5-(trifluoromethyl)-1,3,8,12-tetrazatricyclo[8.4.0.02,7]tetradeca-2(7),3,5-trien-9-one	1875834: Inhibition of PARP7 (unknown origin) by HTRF assay	ic50	0.0008	uM
4-[1-[3-oxo-3-[5-(trifluoromethyl)-1,3,8,11-tetrazatricyclo[7.4.0.02,7]trideca-2(7),3,5-trien-11-yl]propoxy]propan-2-yloxy]-5-(trifluoromethyl)-1H-pyridazin-6-one	1875834: Inhibition of PARP7 (unknown origin) by HTRF assay	ic50	0.0008	uM
6-[4-amino-5-(difluoromethyl)pyrimidin-2-yl]-7-fluoro-2-[(2S,4S)-2-fluoro-4-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]oxy]pentyl]isoquinolin-1-one	2241579: Inhibition of PARP7 in human NCI-H1373 cells assessed as increase in STAT1 phosphorylation at Tyr701 incubated for 48 hrs by LANCE Ultra sandwich assay	ec50	0.0008	uM
(10R)-8-methyl-12-[3-[[(2S)-1-[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]azetidin-2-yl]methoxy]propanoyl]-5-(trifluoromethyl)-1,3,8,12-tetrazatricyclo[8.4.0.02,7]tetradeca-2(7),3,5-trien-9-one	1875834: Inhibition of PARP7 (unknown origin) by HTRF assay	ic50	0.0009	uM
4-[(2S)-1-[3-[(11S)-5-chloro-8-oxa-1,3,13-triazatricyclo[9.4.0.02,7]pentadeca-2(7),3,5-trien-13-yl]-3-oxopropoxy]propan-2-yl]oxy-5-(trifluoromethyl)-1H-pyridazin-6-one	2101350: Inhibition of PARP7 (unknown origin) incubated for 1 hr by chemiluminescence based microplate reader assay	ic50	0.0009	uM
8-methyl-12-[3-[(2S)-2-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]propoxy]propanoyl]-5-(trifluoromethyl)-1,3,8,12-tetrazatricyclo[8.4.0.02,7]tetradeca-2(7),3,5-trien-9-one	1875834: Inhibition of PARP7 (unknown origin) by HTRF assay	ic50	0.0010	uM
4-[(2S)-1-[3-[(11R)-5-chloro-8-oxa-1,3,13-triazatricyclo[9.4.0.02,7]pentadeca-2(7),3,5-trien-13-yl]-3-oxopropoxy]propan-2-yl]oxy-5-(trifluoromethyl)-1H-pyridazin-6-one	1875834: Inhibition of PARP7 (unknown origin) by HTRF assay	ic50	0.0010	uM
4-[(2S)-1-methoxy-3-[3-oxo-3-[(10S)-5-(trifluoromethyl)-8-oxa-1,3,12-triazatricyclo[8.4.0.02,7]tetradeca-2(7),3,5-trien-12-yl]propoxy]propan-2-yl]oxy-5-(trifluoromethyl)-1H-pyridazin-6-one	2142430: Inhibition of PARP7 (unknown origin) using histone as substrate incubated for 1 hr by chemiluminescence assay	ic50	0.0010	uM
(10R)-8-ethenyl-12-[3-[(2S)-2-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]propoxy]propanoyl]-5-(trifluoromethyl)-1,3,8,12-tetrazatricyclo[8.4.0.02,7]tetradeca-2(7),3,5-trien-9-one	1875834: Inhibition of PARP7 (unknown origin) by HTRF assay	ic50	0.0012	uM
4-[(2S)-1-[3-oxo-3-[(10S)-5-(trifluoromethyl)-8-oxa-1,3,12-triazatricyclo[8.4.0.02,7]tetradeca-2(7),3,5-trien-12-yl]propoxy]propan-2-yl]oxy-5-(trifluoromethyl)-1H-pyridazin-6-one	1875834: Inhibition of PARP7 (unknown origin) by HTRF assay	ic50	0.0012	uM
4-[(2S)-2-[[3-[(11R)-5-chloro-8-oxa-1,3,13-triazatricyclo[9.4.0.02,7]pentadeca-2(7),3,5-trien-13-yl]-3-oxopropoxy]methyl]azetidin-1-yl]-5-(trifluoromethyl)-1H-pyridazin-6-one	2101350: Inhibition of PARP7 (unknown origin) incubated for 1 hr by chemiluminescence based microplate reader assay	ic50	0.0012	uM
4-[[(2S)-1-[3-[(11S)-5-chloro-8-oxa-1,3,13-triazatricyclo[9.4.0.02,7]pentadeca-2(7),3,5-trien-13-yl]-3-oxopropoxy]propan-2-yl]amino]-5-(trifluoromethyl)-1H-pyridazin-6-one	2101350: Inhibition of PARP7 (unknown origin) incubated for 1 hr by chemiluminescence based microplate reader assay	ic50	0.0013	uM
4-[[(2S)-1-methoxy-3-[3-oxo-3-[(11S)-5-(trifluoromethyl)-8-oxa-1,3,13-triazatricyclo[9.4.0.02,7]pentadeca-2(7),3,5-trien-13-yl]propoxy]propan-2-yl]amino]-5-(trifluoromethyl)-1H-pyridazin-6-one	2101350: Inhibition of PARP7 (unknown origin) incubated for 1 hr by chemiluminescence based microplate reader assay	ic50	0.0013	uM
4-[(2S)-1-methoxy-3-[3-oxo-3-[(11S)-5-(trifluoromethyl)-8-oxa-1,3,13-triazatricyclo[9.4.0.02,7]pentadeca-2(7),3,5-trien-13-yl]propoxy]propan-2-yl]oxy-5-(trifluoromethyl)-1H-pyridazin-6-one	2101350: Inhibition of PARP7 (unknown origin) incubated for 1 hr by chemiluminescence based microplate reader assay	ic50	0.0014	uM
4-[(2S)-1-[3-oxo-3-[(11S)-5-(trifluoromethyl)-8-oxa-1,3,13-triazatricyclo[9.4.0.02,7]pentadeca-2(7),3,5-trien-13-yl]propoxy]propan-2-yl]oxy-5-(trifluoromethyl)-1H-pyridazin-6-one	2101350: Inhibition of PARP7 (unknown origin) incubated for 1 hr by chemiluminescence based microplate reader assay	ic50	0.0017	uM
4-[[(2S)-1-[3-oxo-3-[(10S)-5-(trifluoromethyl)-8-oxa-1,3,12-triazatricyclo[8.4.0.02,7]tetradeca-2(7),3,5-trien-12-yl]propoxy]propan-2-yl]amino]-5-(trifluoromethyl)-1H-pyridazin-6-one	2142430: Inhibition of PARP7 (unknown origin) using histone as substrate incubated for 1 hr by chemiluminescence assay	ic50	0.0019	uM
4-[(2S)-1-[3-[(11R)-5-chloro-6-(trifluoromethyl)-8-oxa-1,3,13-triazatricyclo[9.4.0.02,7]pentadeca-2,4,6-trien-13-yl]-3-oxopropoxy]propan-2-yl]oxy-5-(trifluoromethyl)-1H-pyridazin-6-one	1875834: Inhibition of PARP7 (unknown origin) by HTRF assay	ic50	0.0020	uM
N-hydroxy-7-[2-[4-[3-[(2S)-2-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]propoxy]propanoyl]piperazin-1-yl]pyrimidin-5-yl]oxyheptanamide	2081197: Inhibition of N-terminal FLAG tagged human PARP7 (400 to 657 residues) preincubated for 10 mins followed by PARP substrate addition and measured after 30 mins by fluorescence based analysis	ic50	0.0020	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tetrachlorodibenzodioxin	decreases response to substance, increases ADP-ribosylation, affects expression, affects reaction, affects binding (+7 more)	24
Particulate Matter	increases abundance, increases expression, decreases expression, increases reaction, affects cotreatment (+1 more)	11
Benzo(a)pyrene	affects expression, affects methylation, increases expression, increases methylation	10
Estradiol	affects expression, affects binding, increases expression, affects cotreatment	8
Tobacco Smoke Pollution	increases expression, affects expression	8
Air Pollutants	increases expression, decreases expression, increases abundance	6
3,4,5,3’,4’-pentachlorobiphenyl	increases expression	4
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	3
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	decreases expression, decreases reaction, increases expression	3
Vehicle Emissions	increases abundance, increases expression	3
Tretinoin	increases expression, decreases expression	3
bisphenol A	decreases expression	2
alpha-naphthoflavone	increases expression, increases reaction, decreases expression	2
Zoledronic Acid	increases expression	2
Cisplatin	decreases expression, increases expression	2
Progesterone	affects cotreatment, increases expression	2
Smoke	increases expression	2
Valproic Acid	increases expression, decreases methylation	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression, increases expression	2
Cyclosporine	affects expression, decreases expression	2
Aflatoxin B1	decreases methylation, increases expression	2
Cadmium Chloride	increases expression, affects expression, increases abundance	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
TAK-243	increases sumoylation	1
SBI-797812	increases activity	1
chloroacetaldehyde	decreases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
lead acetate	increases expression	1

ChEMBL screening assays

48 unique, capped per target: 48 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2382489	Binding	Inhibition of PARP7 (unknown origin) at 10 uM relative to control	Fragment-based ligand design of novel potent inhibitors of tankyrases. — *J Med Chem*

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TS40	HAP1 TIPARP (-) 1	Cancer cell line	Male
CVCL_TS41	HAP1 TIPARP (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for TIPARP across ~30M SureChEMBL compounds — explore on Sugi Predict.