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): 83 total
• Druggable target: yes — 4 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 24.7% of screened cell lines
• MANE Select transcript: NM_015508

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: 8 — 8 protein_coding

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

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
ENSE00001817264	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.

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

292 total, 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

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

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

117 targeting TIPARP, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-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

DepMap (CRISPR cell-line fitness): dependent in 24.7% of screened cell lines.

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)

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): C9JXM5, Q7Z3E1, 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), 3 shown:

• 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

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

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

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): 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 pathways

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 (15): vasculogenesis (GO:0001570), kidney development (GO:0001822), androgen metabolic process (GO:0008209), estrogen metabolic process (GO:0008210), female gonad development (GO:0008585), post-embryonic development (GO:0009791), negative regulation of gene expression (GO:0010629), hemopoiesis (GO:0030097), positive regulation of protein catabolic process (GO:0045732), platelet-derived growth factor receptor signaling pathway (GO:0048008), skeletal system morphogenesis (GO:0048705), smooth muscle tissue development (GO:0048745), roof of mouth development (GO:0060021), face morphogenesis (GO:0060325), 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

Rollup of top GO terms by namespace:

Category	Terms
NAD+-protein mono-ADP-ribosyltransferase activity	3
steroid metabolic process	2
hormone metabolic process	2
pentosyltransferase activity	2
cell differentiation	1
blood vessel morphogenesis	1
animal organ development	1
renal system development	1
gonad development	1
development of primary female sexual characteristics	1
multicellular organism development	1
multicellular organismal process	1
gene expression	1
regulation of gene expression	1
negative regulation of macromolecule biosynthetic process	1
cell development	1
positive regulation of catabolic process	1
protein catabolic process	1
regulation of protein catabolic process	1
positive regulation of protein metabolic process	1
cell surface receptor protein tyrosine kinase signaling pathway	1
skeletal system development	1
animal organ morphogenesis	1
muscle tissue development	1
anatomical structure development	1
anatomical structure morphogenesis	1
head morphogenesis	1
face development	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

Protein interactions and networks

STRING

930 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TIPARP	PARP1	P09874	863
TIPARP	PARP16	Q8N5Y8	736
TIPARP	CYP1A1	P04798	593
TIPARP	PARP6	Q2NL67	580
TIPARP	AHRR	A9YTQ3	572
TIPARP	CYP1B1	Q16678	565
TIPARP	PARP4	Q9UKK3	550
TIPARP	PARP2	Q9UGN5	533
TIPARP	PARP3	Q9Y6F1	533
TIPARP	HABP4	Q5JVS0	530
TIPARP	PARP8	Q8N3A8	523
TIPARP	MYC	P01106	497
TIPARP	TNKS2	Q9H2K2	496
TIPARP	ADPRS	Q9NX46	474
TIPARP	HUWE1	Q7Z6Z7	471

IntAct

5 interactions, top by confidence:

A	B	Type	Score
NCBP2	KPNA4	psi-mi:“MI:0914”(association)	0.530
TIPARP	RPL11	psi-mi:“MI:0915”(physical association)	0.400
TIPARP	LAD1	psi-mi:“MI:0914”(association)	0.350
XRN2	TIPARP	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (1546): TIPARP (Proximity Label-MS), TIPARP (Positive Genetic), TIPARP (Affinity Capture-MS), CLPP (Affinity Capture-MS), RNF114 (Affinity Capture-MS), RNF166 (Affinity Capture-MS), LAD1 (Affinity Capture-MS), TIPARP (Affinity Capture-Western), ABCB7 (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)

ESM2 similar proteins: A2VE78, A4FV61, D2HNY3, D3YYM4, E9Q6D6, O15259, O88974, O95170, P28715, P35689, P55265, P97432, Q14596, Q149N8, Q15047, Q2HJ90, Q4KM95, Q501R9, Q5F3F2, Q5F479, Q5PQT2, Q5R6E1, Q5R6F3, Q5RC94, Q5RF77, Q5VT97, Q642B6, Q68FE8, Q69Z66, Q6P3Z3, Q6ZWE6, Q76CY8, Q7TPQ3, Q7Z3E1, Q810L3, Q8BM47, Q8C1B2, Q8C2S5, Q8K296, Q8ND82

Diamond homologs: A1Z1Q3, A4W960, A7MG20, A8AI35, B4T2X8, B5F961, B5RBF3, B5XXK9, B7LT90, C9Y0V8, D2TT52, D3RKJ0, D5CE05, E1PL40, E1SDF1, O28751, O59182, O75367, O93327, P0A8D6, P0A8D7, P0A8D8, P0C6F6, P0C6T4, P0C6T6, P0C6T8, P0C6T9, P0C6U0, P0C6U1, P0C6U7, P0C6W3, P0C6W5, P0C6W7, P0C6W8, P0C6W9, P0C6X0, P0C6X6, P67341, P67342, P9WK28

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	66
Likely benign	2
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1069 predictions. Top by Δscore:

Variant	Effect	Δscore
3:156694007:T:A	acceptor_gain	1.0000
3:156694015:TTTA:T	acceptor_loss	1.0000
3:156694016:TTA:T	acceptor_loss	1.0000
3:156694018:A:AC	acceptor_loss	1.0000
3:156694018:A:AG	acceptor_gain	1.0000
3:156694018:AGAG:A	acceptor_gain	1.0000
3:156694019:G:GA	acceptor_gain	1.0000
3:156694019:GA:G	acceptor_gain	1.0000
3:156694019:GAGG:G	acceptor_gain	1.0000
3:156694019:GAGGA:G	acceptor_gain	1.0000
3:156694185:CGAG:C	donor_loss	1.0000
3:156694187:AG:A	donor_loss	1.0000
3:156694188:GGT:G	donor_loss	1.0000
3:156694207:TTGAC:T	donor_gain	1.0000
3:156695843:T:A	acceptor_gain	1.0000
3:156695848:T:A	acceptor_gain	1.0000
3:156695861:A:AG	acceptor_gain	1.0000
3:156695862:T:G	acceptor_gain	1.0000
3:156695862:TAGTC:T	acceptor_loss	1.0000
3:156695863:A:AG	acceptor_gain	1.0000
3:156695863:AG:A	acceptor_loss	1.0000
3:156695863:AGTCT:A	acceptor_gain	1.0000
3:156695864:G:GA	acceptor_gain	1.0000
3:156695864:GT:G	acceptor_gain	1.0000
3:156695864:GTC:G	acceptor_gain	1.0000
3:156695864:GTCT:G	acceptor_gain	1.0000
3:156695864:GTCTG:G	acceptor_gain	1.0000
3:156696026:G:GG	donor_gain	1.0000
3:156703587:GA:G	donor_gain	1.0000
3:156703595:T:G	donor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000078051 (3:156692874 T>C), RS1000186877 (3:156677234 G>A), RS1000187550 (3:156685471 G>T), RS1000201034 (3:156681100 A>G), RS1000521073 (3:156676060 T>C), RS1000594080 (3:156687642 A>C), RS1000619245 (3:156679763 G>A), RS1000662485 (3:156685738 C>G), RS1000718605 (3:156675840 T>G), RS1000755073 (3:156680000 A>C), RS1000801257 (3:156682656 C>G), RS1000868420 (3:156673883 T>C), RS1000868790 (3:156684549 C>T), RS1000921407 (3:156687200 A>G), RS1000973407 (3:156689992 G>A)

Disease associations

OMIM: gene MIM:612480 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

12 associations (top):

Study	Trait	p-value
GCST000802_1	Ovarian cancer	3.000000e-07
GCST002748_4	Epithelial ovarian cancer	6.000000e-51
GCST003999_18	Nose size	2.000000e-07
GCST004713_16	Testicular germ cell tumor	7.000000e-09
GCST005667_29	Central corneal thickness	5.000000e-11
GCST007576_384	Chronotype	6.000000e-08
GCST007656_21	Chronic obstructive pulmonary disease or resting heart rate (pleiotropy)	4.000000e-11
GCST010725_61	Malaria	1.000000e-06
GCST010725_81	Malaria	6.000000e-06
GCST010988_120	Adult body size	8.000000e-10
GCST011011_68	Youthful appearance (self-reported)	2.000000e-08
GCST012490_85	Femur bone mineral density x serum urate levels interaction	2.000000e-10

EFO canonical traits (3, from GWAS)

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

4 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 15,755 (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
CHEMBL521686	OLAPARIB	4	13,038
CHEMBL4112930	PAMIPARIB	3	2,114
CHEMBL5095220	SARUPARIB	3	357
CHEMBL5095043	ATAMPARIB	1	246

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

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)

163 measured of 668 human assays (668 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
CHEMBL5177385	IC50	0.611 nM
CHEMBL5183629	IC50	0.806 nM
CHEMBL5202833	IC50	0.87 nM
CHEMBL5173659	IC50	1 nM
US20250333394, Example 29	IC50	1.75 nM	US-20250333394: Tiparp Inhibitor Compounds
CHEMBL5193823	IC50	2 nM
US20250333394, Example 15	IC50	2.15 nM	US-20250333394: Tiparp Inhibitor Compounds
US20250333394, Example 14	IC50	2.17 nM	US-20250333394: Tiparp Inhibitor Compounds
US20250333394, Example 5	IC50	2.3 nM	US-20250333394: Tiparp Inhibitor Compounds
US20250333394, Example 27	IC50	2.34 nM	US-20250333394: Tiparp Inhibitor Compounds
US20250333394, Example 1	IC50	2.4 nM	US-20250333394: Tiparp Inhibitor Compounds
US20250333394, Example 23	IC50	2.74 nM	US-20250333394: Tiparp Inhibitor Compounds
US20250333394, Example 22	IC50	2.8 nM	US-20250333394: Tiparp Inhibitor Compounds
CHEMBL5204396	IC50	3.1 nM
US20250333394, Example 12	IC50	3.16 nM	US-20250333394: Tiparp Inhibitor Compounds
US20250333394, Example 16	IC50	3.34 nM	US-20250333394: Tiparp Inhibitor Compounds
US20250333394, Example 6	IC50	3.43 nM	US-20250333394: Tiparp Inhibitor Compounds
US20250333394, Example 2	IC50	3.75 nM	US-20250333394: Tiparp Inhibitor Compounds
US20250333394, Example 7	IC50	3.79 nM	US-20250333394: Tiparp Inhibitor Compounds
US20250333394, Example 13	IC50	3.79 nM	US-20250333394: Tiparp Inhibitor Compounds
US20250333394, Example 9	IC50	4.32 nM	US-20250333394: Tiparp Inhibitor Compounds
US20250333394, Example 3	IC50	4.74 nM	US-20250333394: Tiparp Inhibitor Compounds
US20250333394, Example 17	IC50	5 nM	US-20250333394: Tiparp Inhibitor Compounds
US20250333394, Example 28	IC50	5.69 nM	US-20250333394: Tiparp Inhibitor Compounds
US20250333394, Example 4	IC50	5.7 nM	US-20250333394: Tiparp Inhibitor Compounds
US20250333394, Example 19	IC50	5.79 nM	US-20250333394: Tiparp Inhibitor Compounds
US20250333394, Example 18	IC50	5.86 nM	US-20250333394: Tiparp Inhibitor Compounds
US20250333394, Example 20	IC50	6.95 nM	US-20250333394: Tiparp Inhibitor Compounds
US20250333394, Example 8	IC50	8.79 nM	US-20250333394: Tiparp Inhibitor Compounds
US20250333394, Example 10	IC50	10.1 nM	US-20250333394: Tiparp Inhibitor Compounds
US20250333394, Example 11	IC50	10.9 nM	US-20250333394: Tiparp Inhibitor Compounds
US20250333394, Example 21	IC50	12.9 nM	US-20250333394: Tiparp Inhibitor Compounds
5-[6-[(1-acetylpiperidin-4-yl)oxy]-5-fluoro-1-methyl-2,3-dihydro-1H-isoindol-2-yl]-4-(trifluoromethyl)-2,3-dihydropyridazin-3-one	IC50	550 nM	US-10550105: Pyridazinones as PARP7 inhibitors
6-[4-[3-[[(1R)-2-[6-oxo-5-(trifluoromethyl)diazinan-4-yl]-1,3-dihydroisoindol-1-yl]methoxy]benzoyl]piperazin-1-yl]pyridine-3-carbonitrile	IC50	550 nM	US-10550105: Pyridazinones as PARP7 inhibitors
6-(4-[[3-([1-[6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl]piperidin-2-yl]methoxy)phenyl]carbonyl]piperazin-1-yl)pyridine-3-carbonitrile	IC50	550 nM	US-10550105: Pyridazinones as PARP7 inhibitors
6-[4-[(3S,5R)-5-[[(2S)-1-[3-oxo-4-(trifluoromethyl)-4H-pyridazin-5-yl]pyrrolidin-2-yl]methoxy]piperidine-3-carbonyl]piperazin-1-yl]pyridine-3-carbonitrile	IC50	550 nM	US-10550105: Pyridazinones as PARP7 inhibitors
6-[4-[(1S,3S)-3-[[(2S)-1-[6-oxo-5-(trifluoromethyl)diazinan-4-yl]pyrrolidin-2-yl]methoxy]cyclohexanecarbonyl]piperazin-1-yl]pyridine-3-carbonitrile	IC50	550 nM	US-10550105: Pyridazinones as PARP7 inhibitors
6-[4-[(1S,3R)-3-[[(2S)-1-[6-oxo-5-(trifluoromethyl)diazinan-4-yl]pyrrolidin-2-yl]methoxy]cyclohexanecarbonyl]piperazin-1-yl]pyridine-3-carbonitrile	IC50	550 nM	US-10550105: Pyridazinones as PARP7 inhibitors
6-[4-[(1R,3S)-3-[[(2S)-1-[6-oxo-5-(trifluoromethyl)diazinan-4-yl]pyrrolidin-2-yl]methoxy]cyclohexanecarbonyl]piperazin-1-yl]pyridine-3-carbonitrile	IC50	550 nM	US-10550105: Pyridazinones as PARP7 inhibitors
6-(4-[[3-([4-[6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl]morpholin-3-yl]methoxy)phenyl]carbonyl]piperazin-1-yl)pyridine-3-carbonitrile	IC50	550 nM	US-10550105: Pyridazinones as PARP7 inhibitors
2-[[(2S)-1-[6-oxo-5-(trifluoromethyl)diazinan-4-yl]pyrrolidin-2-yl]methoxy]-N-[4-(pyridin-2-ylamino)cyclohexyl]acetamide	IC50	550 nM	US-10550105: Pyridazinones as PARP7 inhibitors
3-[[(2S)-1-[6-oxo-5-(trifluoromethyl)diazinan-4-yl]pyrrolidin-2-yl]methoxy]-N-[4-(pyridin-2-ylamino)cyclohexyl]propanamide	IC50	550 nM	US-10550105: Pyridazinones as PARP7 inhibitors
6-[4-[4-[[(2S)-1-[6-oxo-5-(trifluoromethyl)diazinan-4-yl]pyrrolidin-2-yl]methoxy]cyclohexanecarbonyl]piperazin-1-yl]pyridine-3-carbonitrile	IC50	550 nM	US-10550105: Pyridazinones as PARP7 inhibitors
2-[[(2S)-1-[6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl]pyrrolidin-2-yl]methoxy]-N-[4-(pyridin-2-yloxy)cyclohexyl]acetamide	IC50	550 nM	US-10550105: Pyridazinones as PARP7 inhibitors
3-[[(2S)-1-[6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl]pyrrolidin-2-yl]methoxy]-N-[4-(pyridin-2-yloxy)cyclohexyl]propanamide	IC50	550 nM	US-10550105: Pyridazinones as PARP7 inhibitors
N-(3-[[(2S)-1-[6-oxo-5-(trifluoromethyl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1,6-dihydropyridazin-4-yl]pyrrolidin-2-yl]methoxy]phenyl)prop-2-enamide	IC50	550 nM	US-10550105: Pyridazinones as PARP7 inhibitors
6-(4-[2-[methyl([2-[(2S)-1-[6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl]pyrrolidin-2-yl]ethyl)amino]acetyl]piperazin-1-yl)pyridine-3-carbonitrile	IC50	550 nM	US-10550105: Pyridazinones as PARP7 inhibitors
6-[4-[3-[[(1R)-2-[6-oxo-5-(trifluoromethyl)diazinan-4-yl]-1,3-dihydroisoindol-1-yl]methoxy]propanoyl]piperazin-1-yl]pyridine-3-carbonitrile	IC50	550 nM	US-10550105: Pyridazinones as PARP7 inhibitors
N-(4-[(5-cyanopyridin-2-yl)oxy]cyclohexyl]-3-[[(2S)-1-[6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl]pyrrolidin-2-yl]methoxy]propanamide	IC50	550 nM	US-10550105: Pyridazinones as PARP7 inhibitors

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

130 with measured affinity, of 212 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
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
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
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
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
(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
4-[[(2S)-1-[3-oxo-3-[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	0.0021	uM
N’-hydroxy-N-[2-[4-[3-[(2S)-2-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]propoxy]propanoyl]piperazin-1-yl]pyrimidin-5-yl]heptanediamide	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	0.0024	uM
N-hydroxy-2-[4-[3-[(2S)-2-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]propoxy]propanoyl]piperazin-1-yl]pyrimidine-5-carboxamide	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	0.0027	uM
4-[(2S)-1-[3-oxo-3-[5-(trifluoromethyl)-1,3,8,13-tetrazatricyclo[9.4.0.02,7]pentadeca-2(7),3,5-trien-13-yl]propoxy]propan-2-yl]oxy-5-(trifluoromethyl)-1H-pyridazin-6-one	1875834: Inhibition of PARP7 (unknown origin) by HTRF assay	ic50	0.0031	uM
(E)-N-hydroxy-3-[4-[[2-[4-[3-[(2S)-2-[[6-oxo-5-(trifluoromethyl)-1H-pyridazin-4-yl]amino]propoxy]propanoyl]piperazin-1-yl]pyrimidin-5-yl]oxymethyl]phenyl]prop-2-enamide	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	0.0031	uM
4-[[(2S)-1-[3-oxo-3-[(10R)-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	0.0033	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tetrachlorodibenzodioxin	affects reaction, decreases activity, increases ADP-ribosylation, affects expression, affects binding (+7 more)	24
Benzo(a)pyrene	affects expression, affects methylation, increases expression, increases methylation	10
Particulate Matter	increases abundance, increases expression, decreases expression, increases reaction, affects cotreatment (+1 more)	10
Estradiol	affects expression, affects binding, increases expression, affects cotreatment	8
Tobacco Smoke Pollution	affects expression, increases expression	8
3,4,5,3’,4’-pentachlorobiphenyl	increases expression	4
Air Pollutants	increases abundance, increases expression, decreases expression	4
sodium arsenite	increases abundance, increases expression, decreases expression, affects cotreatment	3
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	decreases reaction, increases expression, decreases expression	3
Vehicle Emissions	increases expression, increases abundance	3
Tretinoin	decreases expression, increases 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	decreases methylation, increases expression	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	affects expression, increases abundance, increases expression	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)

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