POLQ

Summary

POLQ (DNA polymerase theta, HGNC:9186) is a protein-coding gene on chromosome 3q13.33, encoding DNA polymerase theta (O75417). Low-fidelity DNA polymerase with a helicase activity that promotes microhomology-mediated end-joining (MMEJ), an alternative non-homologous end-joining (NHEJ) machinery required to repair double-strand breaks in DNA during mitosis. It is a selective cancer dependency (DepMap: 19.3% of cell lines).

Enables several functions, including catalytic activity, acting on DNA; identical protein binding activity; and magnesium ion binding activity. Involved in DNA metabolic process; negative regulation of double-strand break repair via homologous recombination; and protein homooligomerization. Located in Golgi apparatus; cytosol; and nucleoplasm. Is active in mitochondrial nucleoid; nucleus; and site of double-strand break.

Source: NCBI Gene 10721 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 3,601 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 19.3% of screened cell lines
• MANE Select transcript: NM_199420

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9186
Approved symbol	POLQ
Name	DNA polymerase theta
Location	3q13.33
Locus type	gene with protein product
Status	Approved
Aliases	POLH
Ensembl gene	ENSG00000051341
Ensembl biotype	protein_coding
OMIM	604419
Entrez	10721

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 4 protein_coding, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000264233, ENST00000474243, ENST00000488282, ENST00000683498, ENST00000932951, ENST00000932952, ENST00000932953

RefSeq mRNA: 1 — MANE Select: NM_199420 NM_199420

CCDS: CCDS33833

Canonical transcript exons

ENST00000264233 — 30 exons

Exon	Start	End
ENSE00001012319	121436122	121436275
ENSE00001012327	121439992	121440116
ENSE00001012336	121432918	121433033
ENSE00001078698	121485041	121485184
ENSE00001078703	121460050	121460234
ENSE00001078706	121473350	121473487
ENSE00001078710	121481572	121481812
ENSE00001078711	121498477	121498670
ENSE00001078712	121471990	121472164
ENSE00001078713	121493478	121493721
ENSE00001078715	121487302	121490408
ENSE00001078718	121496808	121496932
ENSE00001078721	121509561	121509703
ENSE00001078722	121483386	121483582
ENSE00001149642	121511887	121512029
ENSE00001235285	121510039	121510243
ENSE00001235300	121519871	121520083
ENSE00001235330	121532990	121533209
ENSE00001235341	121537100	121537208
ENSE00001235348	121539433	121539589
ENSE00001235355	121541349	121541479
ENSE00001235361	121544727	121544906
ENSE00001235367	121545715	121545988
ENSE00001858247	121431431	121432417
ENSE00003503491	121476540	121476733
ENSE00003529215	121449315	121449426
ENSE00003640944	121529645	121529792
ENSE00003658205	121467519	121467640
ENSE00003668918	121522003	121522149
ENSE00003693250	121468305	121468431

Expression profiles

Bgee: expression breadth ubiquitous, 166 present calls, max score 87.92.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 4.3350 / max 274.0797, expressed in 982 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
44093	3.9700	961
44094	0.2505	111
44092	0.1145	52

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	87.92	gold quality
oocyte	CL:0000023	82.97	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.10	gold quality
ventricular zone	UBERON:0003053	79.88	gold quality
esophagus squamous epithelium	UBERON:0006920	75.20	gold quality
bone marrow	UBERON:0002371	74.44	gold quality
ganglionic eminence	UBERON:0004023	73.45	gold quality
bone marrow cell	CL:0002092	73.25	gold quality
squamous epithelium	UBERON:0006914	73.04	gold quality
hair follicle	UBERON:0002073	72.45	gold quality
trabecular bone tissue	UBERON:0002483	72.19	gold quality
stromal cell of endometrium	CL:0002255	71.89	gold quality
epithelium of esophagus	UBERON:0001976	71.35	gold quality
embryo	UBERON:0000922	71.09	gold quality
mucosa of transverse colon	UBERON:0004991	70.98	gold quality
gingival epithelium	UBERON:0001949	70.94	silver quality
cervix squamous epithelium	UBERON:0006922	70.43	gold quality
esophagus mucosa	UBERON:0002469	69.46	gold quality
mucosa of paranasal sinus	UBERON:0005030	69.46	silver quality
lower esophagus mucosa	UBERON:0035834	69.37	gold quality
rectum	UBERON:0001052	69.07	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	68.99	gold quality
vermiform appendix	UBERON:0001154	67.40	gold quality
adrenal tissue	UBERON:0018303	67.38	gold quality
diaphragm	UBERON:0001103	65.95	gold quality
tibia	UBERON:0000979	65.70	silver quality
epithelium of bronchus	UBERON:0002031	65.04	gold quality
ileal mucosa	UBERON:0000331	64.76	silver quality
olfactory segment of nasal mucosa	UBERON:0005386	64.45	gold quality
bronchial epithelial cell	CL:0002328	64.34	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.47
E-GEOD-81383	no	172.91

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

101 targeting POLQ, 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-4262	100.00	73.26	3931
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-548P	99.98	72.25	3784
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-545-3P	99.95	70.74	2783

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 19.3% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• DNA polymerase theta purified from human cells is a high-fidelity enzyme. (PMID:12051913)
• the isolation of the full-length human DNA POLQ gene, and an initial characterization of its gene product, DNA polymerase theta (PMID:14576298)
• DNA Pol theta has a specialized function in lymphocytes and in tumor progression (PMID:14735462)
• POLQ has a high efficiency in by-passing DNA damage. (PMID:15496986)
• analysis of human DNA polymerase eta error-prone synthesis on DNA deoxyadenosine adducts (PMID:16188888)
• The results demonstrate that activation of a UV-induced DNA damage response pathway, involving phosphorylation of RPA p34 by DNA-PK, is enhanced in cells lacking poleta. (PMID:16520097)
• Pol eta can play an important role in determining the cellular sensitivity to therapeutic agents. (PMID:16603639)
• DNA polymerase eta (Poleta) is responsible for efficient translesion synthesis (TLS) past cis-syn cyclobutane thymine dimers (TT dimers), the major DNA lesions induced by UV irradiation. (PMID:16824193)
• Human DNA polymerase eta selectively produces a two-base deletion in copying the N2-guanyl adduct of 2-amino-3-methylimidazo[4,5-f]quinoline but not the C8 adduct at the NarI G3 site (PMID:16835218)
• The enzymatic reactions with human DNA polymerase eta on oxidative products of guanine and 8-oxoG, is investigated. (PMID:17150533)
• Evolutionary conservation of efficient T[CPD]T bypass by HsPoleta and AtPoleta may reflect a high degree of exposure of human skin and plants to solar UV-B radiation (PMID:18366182)
• When copying undamaged DNA, DNA polymerase theta generates single base errors at rates 10- to more than 100-fold higher than for other family A members. (PMID:18503084)
• Domain mapping of the 98-kDa enzyme by limited proteolysis and NaBH(4) cross-linking with a base excision repair intermediate revealed that the dRP lyase active site resides in a 24-kDa domain of Pol theta. (PMID:19188258)
• Data show that POLQ overexpression may be a promising genetic instability and prognostic marker for breast cancer. (PMID:20624954)
• overexpression in breast cancer confers an adverse prognosis and is associated with key cancer pathways (PMID:20700469)
• POLQ possesses a DNA polymerase activity that appears to be template independent and allows efficient extension of single-stranded DNA as well as duplex DNA with either protruding or multiply mismatched 3’-OH termini. (PMID:22135286)
• Use fluorescence resonance energy transfer to monitor assembly of the human replicative polymerase holoenzyme. (PMID:23577232)
• A role for DNA polymerase theta; in promoting replication through oxidative DNA lesion, thymine glycol, in human cells. (PMID:24648516)
• A DNA repair variant in POLQ (c.-1060A > G) is associated to hereditary breast cancer patients. (PMID:25409685)
• These results suggest that variants in the POLQ gene may be associated with the risk of Luminal breast cancer (PMID:25417172)
• depletion of Poltheta; has a synergistic effect on cell survival in the absence of BRCA genes, suggesting that the inhibition of this mutagenic polymerase represents a valid therapeutic avenue for tumours carrying mutations in homology-directed repair genes (PMID:25642960)
• results reveal a synthetic lethal relationship between the homologous-recombination pathway and Poltheta;-mediated repair in epithelial ovarian cancers, and identify Poltheta; as a novel druggable target for cancer therapy (PMID:25642963)
• Microhomology-mediated end-joining is dependent on Poltheta; in human cells. (PMID:25643323)
• Polymerase theta; uses a specialized thumb subdomain to establish unique upstream contacts to the primer DNA strand. (PMID:25775267)
• Our results indicate that there is a synthetic lethal relationship between pol theta;-mediated DNA repair and homologous recombination pathways (PMID:27533083)
• This article summarizes work on the expression and purification of the full-length protein, and then focus on the design, expression, and purification of an active C-terminal polymerase fragment. Strategies to obtain and improve crystals of a ternary POLQ complex (enzyme:DNA:nucleotide) are also presented, along with key elements of the structure. (PMID:28668117)
• Cells doubly deficient in Pol theta; and Lig4 exhibit 100% gene-targeting efficiency because of virtually no random integration events. (PMID:28695890)
• Data suggest that error-free DNA replication through 3-deaza-3-methyladenine adduct is mediated via three different pathways dependent upon POL-iota/POL-kappa, POL-theta, and POL-zeta. (PMID:28939775)
• results suggest that bypass of Tg by Pol theta; results in mutations opposite the lesion, as well as frameshift mutations (PMID:29243925)
• Data suggest that translesion DNA synthesis mediated by (1) POLI-dependent pathway (2) REV1- and POLN-dependent pathway, or (3) POLtheta-dependent pathway occur in predominantly error-free manner in human cells. (POLI = DNA polymerase iota; REV1 = DNA repair protein-REV1; POLN = DNA polymerase nu; POLtheta = DNA polymerase theta) (PMID:29330301)
• Importantly, p53 defects or depletion unexpectedly allow mutagenic RAD52 and POLtheta; pathways to hijack stalled replication forks, which the authors find reflected in p53 defective breast-cancer patient COSMIC mutational signatures. These data uncover p53 as a keystone regulator of replication homeostasis within a DNA restart network. (PMID:29334356)
• Heightened Poltheta; expression levels were also associated with elevated mtDNA mutation rates in a selected panel of human tumor tissues, suggesting that this protein can influence mutational frequencies in tumors. T (PMID:29509408)
• Based on previous studies and gene ontology database, we found that POLQ encoding DNA polymerase theta enzyme and FNIP1 encoding tumor suppressor folliculin-interacting protein might have contributed to the Interdigitating dendritic cell sarcoma (IDCS). Our study provides potential causative genetic factors of IDCS and plays a role in advancing the understanding of IDCS pathogenesis (PMID:30099721)
• Expanded Substrate Scope of DNA Polymerase theta; and DNA Polymerase beta: Lyase Activity on 5’-Overhangs and Clustered Lesions. (PMID:30299084)
• Rev1 polymerase and Poltheta; conduct translesion synthesis opposite 1,N(6)-ethenodeoxyadenosine via alternative error-prone pathways (PMID:30808656)
• Poltheta; shows a strong preference for adding deoxyribonucleotides to RNA, but can also add ribonucleotides with relatively high efficiency in particular sequence contexts; this unique activity of Poltheta; will become invaluable for applications requiring 3’ terminal modification of RNA and potentially enzymatic synthesis of RNA (PMID:30818397)
• RAD52 and POLQ are both synthetic lethal with loss of the BRCA1 and BRCA2 tumor suppressor genes. Furthermore, RAD52 and POLQ have been implicated in chromosomal break repair events that use flanking repeats to restore the chromosome. Combined disruption of RAD52 and POLQ causes at least additive hypersensitivity to cisplatin and a synthetic reduction in replication fork restart velocity. (PMID:31381562)
• The roles of polymerases nu and theta in replicative bypass of O (6)- and N (2)-alkyl-2’-deoxyguanosine lesions in human cells. (PMID:32098870)
• Genetic evidence for reconfiguration of DNA polymerase theta active site for error-free translesion synthesis in human cells. (PMID:32169903)
• DNA polymerase theta (Poltheta) - an error-prone polymerase necessary for genome stability. (PMID:32302896)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	polq	ENSDARG00000044622
mus_musculus	Polq	ENSMUSG00000034206
rattus_norvegicus	Polq	ENSRNOG00000002471
drosophila_melanogaster	PolQ	FBGN0002905
caenorhabditis_elegans		WBGENE00020964

Paralogs (8): MTREX (ENSG00000039123), ASCC3 (ENSG00000112249), DDX60 (ENSG00000137628), SNRNP200 (ENSG00000144028), HFM1 (ENSG00000162669), HELQ (ENSG00000163312), DDX60L (ENSG00000181381), SKIC2 (ENSG00000204351)

Protein

Protein identifiers

DNA polymerase theta — O75417 (reviewed: O75417)

Alternative names: DNA polymerase eta

All UniProt accessions (2): A0A804HJJ9, O75417

UniProt curated annotations — full annotation on UniProt →

Function. Low-fidelity DNA polymerase with a helicase activity that promotes microhomology-mediated end-joining (MMEJ), an alternative non-homologous end-joining (NHEJ) machinery required to repair double-strand breaks in DNA during mitosis. MMEJ is an error-prone repair pathway that produces deletions of sequences from the strand being repaired and promotes genomic rearrangements, such as telomere fusions, some of them leading to cellular transformation. MMEJ is required during mitosis to repair persistent double-strand breaks that originate in S-phase. Although error-prone, MMEJ protects against chromosomal instability and tumorigenesis. The polymerase acts by binding directly the 2 ends of resected double-strand breaks, allowing microhomologous sequences in the overhangs to form base pairs. It then extends each strand from the base-paired region using the opposing overhang as a template. Requires partially resected DNA containing 2 to 6 base pairs of microhomology to perform MMEJ. The polymerase lacks proofreading activity and is highly promiscuous: unlike most polymerases, promotes extension of ssDNA and partial ssDNA (pssDNA) substrates. When the ends of a break do not contain terminal microhomology must identify embedded complementary sequences through a scanning step. Also acts as a DNA helicase, promoting dissociation of the replication protein A complex (RPA/RP-A), composed of RPA1, RPA2 and RPA3, from resected double-strand breaks to allow their annealing and subsequent joining by MMEJ. Removal of RPA/RP-A complex proteins prevents RAD51 accumulation at resected ends, thereby inhibiting homology-recombination repair (HR) pathway. Also shows RNA-directed DNA polymerase activity to mediate DNA repair in vitro; however this activity needs additional evidence in vivo. May also have lyase activity. Involved in somatic hypermutation of immunoglobulin genes, a process that requires the activity of DNA polymerases to ultimately introduce mutations at both A/T and C/G base pairs. POLQ-mediated end joining activity is involved in random integration of exogenous DNA hampers.

Subunit / interactions. Homomultimer; forms homodimers and homotetramers. Interacts with RAD51. Interacts with ORC2 and ORC4. Interacts with RHNO1; interaction takes place during mitosis and promotes POLQ recruitment to DNA damage sites. Interacts (when phosphorylated) with TOPBP1 (via BRCT domains 7 and 8); promoting POLQ recruitment to DNA damage sites.

Subcellular location. Nucleus. Chromosome.

Tissue specificity. Highly expressed in testis.

Post-translational modifications. Phosphorylated by PLK1; promoting interaction with TOPBP1 and recruitment to DNA damage sites.

Disease relevance. Breast cancer (BC) [MIM:114480] A common malignancy originating from breast epithelial tissue. Breast neoplasms can be distinguished by their histologic pattern. Invasive ductal carcinoma is by far the most common type. Breast cancer is etiologically and genetically heterogeneous. Important genetic factors have been indicated by familial occurrence and bilateral involvement. Mutations at more than one locus can be involved in different families or even in the same case. The gene represented in this entry may be involved in disease pathogenesis.

Activity regulation. Specifically inhibited by the antibiotic novobiocin. The polymerase activity is specifically inhibited by the small molecule ART558. Novobiocin and ART558 confer specific killing of BRCA1/2-deficient cells and synergize with the poly [ADP-ribose] polymerase (PARP) inhibitor olaparib.

Domain organisation. The loop 2 region is involved in the binding of the 2 ends of resected double-strand breaks and homomultimerization.

Similarity. Belongs to the DNA polymerase type-A family.

Isoforms (2)

UniProt ID	Names	Canonical?
O75417-1	1	yes
O75417-2	2

RefSeq proteins (1): NP_955452* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001098	DNA-dir_DNA_pol_A_palm_dom	Domain
IPR001650	Helicase_C-like	Domain
IPR002298	DNA_polymerase_A	Family
IPR011545	DEAD/DEAH_box_helicase_dom	Domain
IPR012337	RNaseH-like_sf	Homologous_superfamily
IPR014001	Helicase_ATP-bd	Domain
IPR019760	DNA-dir_DNA_pol_A_CS	Conserved_site
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR036397	RNaseH_sf	Homologous_superfamily
IPR043502	DNA/RNA_pol_sf	Homologous_superfamily
IPR046931	HTH_61	Domain
IPR048960	POLQ-like_helical	Domain
IPR057220	DUF7898	Domain

Pfam: PF00270, PF00271, PF00476, PF20470, PF21099, PF25453

Catalyzed reactions (Rhea), 2 shown:

• ATP + H2O = ADP + phosphate + H(+) (RHEA:13065)
• DNA(n) + a 2’-deoxyribonucleoside 5’-triphosphate = DNA(n+1) + diphosphate (RHEA:22508)

UniProt features (199 total): helix 76, strand 59, turn 14, modified residue 11, region of interest 10, mutagenesis site 8, binding site 5, sequence conflict 5, compositionally biased region 4, domain 2, splice variant 2, chain 1, short sequence motif 1, sequence variant 1

Structure

Experimental structures (PDB)

33 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
9YSI	X-RAY DIFFRACTION	2
7ZUS	X-RAY DIFFRACTION	2.26
8E24	X-RAY DIFFRACTION	2.34
9D6N	X-RAY DIFFRACTION	2.43
8E23	X-RAY DIFFRACTION	2.59
9OSW	ELECTRON MICROSCOPY	2.67
9YSH	X-RAY DIFFRACTION	2.71
7ZX1	X-RAY DIFFRACTION	2.83
5AGA	X-RAY DIFFRACTION	2.9
9OSY	ELECTRON MICROSCOPY	2.9
7ZX0	X-RAY DIFFRACTION	2.99
9C5Q	ELECTRON MICROSCOPY	3.1
9AU5	ELECTRON MICROSCOPY	3.11
5A9F	X-RAY DIFFRACTION	3.2
8W0A	ELECTRON MICROSCOPY	3.2
9BP9	ELECTRON MICROSCOPY	3.21
9BPA	ELECTRON MICROSCOPY	3.21
8GD7	X-RAY DIFFRACTION	3.24
6XBU	X-RAY DIFFRACTION	3.29
9BH6	ELECTRON MICROSCOPY	3.3
9D6O	X-RAY DIFFRACTION	3.31
9AU9	ELECTRON MICROSCOPY	3.32
9AU8	ELECTRON MICROSCOPY	3.44
9ASJ	ELECTRON MICROSCOPY	3.5
9ASL	ELECTRON MICROSCOPY	3.5
9BH7	ELECTRON MICROSCOPY	3.5
9BH9	ELECTRON MICROSCOPY	3.5
9BHA	ELECTRON MICROSCOPY	3.5
5A9J	X-RAY DIFFRACTION	3.55
9ASK	ELECTRON MICROSCOPY	3.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75417-F1	59.68	0.13

Functional residue map

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

Ligand- & substrate-binding residues (5): 96; 115–122; 2330; 2331; 2540

Post-translational modifications (11): 990, 1289, 1482, 1486, 1488, 1493, 1555, 1563, 1628, 1635, 1755

Mutagenesis-validated functional residues (8):

Position	Phenotype
121	abolished atpase activity.
1482–1493	in 4s-p mutant; decreased phosphorylation by plk1, leading to impaired interaction with topbp1 and recruitment to dna da
1977	decreased protein stability.
2181	impaired ability to bypasse abasic sites.
2202	impaired ability to bypasse abasic sites. in pol-theta(rr) mutant; abolished polymerase activity; when associated with v
2254	impaired ability to bypasse abasic sites.
2254	in pol-theta(rr) mutant; abolished polymerase activity; when associated with a-2202.
2540–2541	abolishes dna polymerase activity.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-5685939	HDR through MMEJ (alt-NHEJ)

MSigDB gene sets: 423 (showing top): GOBP_DNA_TEMPLATED_DNA_REPLICATION_MAINTENANCE_OF_FIDELITY, GOBP_REGULATION_OF_DOUBLE_STRAND_BREAK_REPAIR, GOBP_RNA_TEMPLATED_DNA_BIOSYNTHETIC_PROCESS, GOBP_RESPONSE_TO_UV_C, GOBP_REGULATION_OF_DNA_RECOMBINATION, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, WANG_CLIM2_TARGETS_UP, KANG_DOXORUBICIN_RESISTANCE_UP, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_CELLULAR_RESPONSE_TO_UV, TGCACTT_MIR519C_MIR519B_MIR519A, CMYB_01, GOBP_CELLULAR_RESPONSE_TO_LIGHT_STIMULUS, GOBP_NEGATIVE_REGULATION_OF_DNA_REPAIR, CGGAARNGGCNG_UNKNOWN

GO Biological Process (14): DNA synthesis involved in DNA repair (GO:0000731), DNA repair (GO:0006281), base-excision repair (GO:0006284), double-strand break repair (GO:0006302), DNA damage response (GO:0006974), somatic hypermutation of immunoglobulin genes (GO:0016446), replication fork processing (GO:0031297), error-prone translesion synthesis (GO:0042276), protein homooligomerization (GO:0051260), double-strand break repair via alternative nonhomologous end joining (GO:0097681), negative regulation of double-strand break repair via homologous recombination (GO:2000042), DNA replication (GO:0006260), DNA-templated DNA replication (GO:0006261), RNA-templated DNA biosynthetic process (GO:0006278)

GO Molecular Function (21): magnesium ion binding (GO:0000287), DNA helicase activity (GO:0003678), chromatin binding (GO:0003682), damaged DNA binding (GO:0003684), DNA-directed DNA polymerase activity (GO:0003887), RNA-directed DNA polymerase activity (GO:0003964), ATP binding (GO:0005524), ATP hydrolysis activity (GO:0016887), single-stranded DNA helicase activity (GO:0017116), identical protein binding (GO:0042802), 5’-deoxyribose-5-phosphate lyase activity (GO:0051575), nucleotide binding (GO:0000166), nucleic acid binding (GO:0003676), DNA binding (GO:0003677), catalytic activity (GO:0003824), helicase activity (GO:0004386), protein binding (GO:0005515), transferase activity (GO:0016740), nucleotidyltransferase activity (GO:0016779), hydrolase activity (GO:0016787), DNA polymerase activity (GO:0034061)

GO Cellular Component (8): nucleus (GO:0005634), nucleoplasm (GO:0005654), Golgi apparatus (GO:0005794), cytosol (GO:0005829), site of double-strand break (GO:0035861), mitochondrial nucleoid (GO:0042645), site of DNA damage (GO:0090734), chromosome (GO:0005694)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Homology Directed Repair	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA repair	3
DNA biosynthetic process	3
binding	3
cellular anatomical structure	3
DNA metabolic process	2
DNA polymerase activity	2
ATP-dependent activity	2
catalytic activity	2
intracellular membrane-bounded organelle	2
cytoplasm	2
intracellular membraneless organelle	2
DNA damage response	1
cellular response to stress	1
somatic diversification of immune receptors via somatic mutation	1
somatic diversification of immunoglobulins	1
DNA-templated DNA replication maintenance of fidelity	1
translesion synthesis	1
protein complex oligomerization	1
double-strand break repair via nonhomologous end joining	1
double-strand break repair via homologous recombination	1
regulation of double-strand break repair via homologous recombination	1
negative regulation of DNA recombination	1
negative regulation of double-strand break repair	1
DNA replication	1
metal ion binding	1
helicase activity	1
ATP-dependent activity, acting on DNA	1
DNA binding	1
RNA-templated DNA biosynthetic process	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
ribonucleoside triphosphate phosphatase activity	1
DNA helicase activity	1
protein binding	1
carbon-oxygen lyase activity	1
catalytic activity, acting on DNA	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
nucleic acid binding	1
molecular_function	1

Protein interactions and networks

STRING

1748 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
POLQ	POLG	P54098	891
POLQ	UNG	P13051	852
POLQ	GOLGB1	Q14789	770
POLQ	LIG3	P49916	765
POLQ	POLD1	P28340	700
POLQ	REV3L	O60673	686
POLQ	PARP1	P09874	678
POLQ	LIG4	P49917	665
POLQ	XRCC1	P18887	662
POLQ	RBBP8	Q99708	641
POLQ	XRCC6	P12956	640
POLQ	POLE	Q07864	639
POLQ	POLL	Q9UGP5	632
POLQ	XRCC5	P13010	628
POLQ	EXO1	Q9UQ84	625

IntAct

7 interactions, top by confidence:

A	B	Type	Score
POLQ	RBM25	psi-mi:“MI:0915”(physical association)	0.560
Atp2a2	ESYT2	psi-mi:“MI:0914”(association)	0.350
HSPA4	HSPA8	psi-mi:“MI:0914”(association)	0.350
POLQ	TCERG1	psi-mi:“MI:0914”(association)	0.350
MAGEA9	CIBAR1	psi-mi:“MI:0914”(association)	0.350
PTGES3	SBNO1	psi-mi:“MI:0914”(association)	0.350

BioGRID (30): POLQ (Affinity Capture-MS), POLQ (Affinity Capture-MS), POLQ (Affinity Capture-MS), POLQ (Affinity Capture-RNA), POLQ (Affinity Capture-MS), RBM25 (Proximity Label-MS), POLQ (Affinity Capture-MS), POLQ (Affinity Capture-MS), POLQ (Affinity Capture-MS), MRE11A (Affinity Capture-Western), XRCC1 (Affinity Capture-Western), POLQ (Affinity Capture-MS), TCERG1 (Affinity Capture-MS), PRPF40A (Affinity Capture-MS), RBM25 (Affinity Capture-MS)

ESM2 similar proteins: A0A0P0V4R0, A0A1D5PRR9, A4IG62, A9UMG5, B4JNS2, F1R345, F4HQE2, F4KFV7, O75417, P0C928, P42285, Q14527, Q16X92, Q28E61, Q2VPA6, Q43093, Q56YN3, Q5JK52, Q5U2U7, Q5W9E7, Q5ZJT0, Q5ZLV4, Q60446, Q642J4, Q6PCL9, Q6PCN7, Q6PFE3, Q7XT07, Q8CGS6, Q8H2D5, Q8IYB8, Q8IYD8, Q8K394, Q94BR5, Q95216, Q9BWT3, Q9CZU3, Q9DG67, Q9FF61, Q9FT73

Diamond homologs: A0FLQ6, O08307, O34996, O51498, O52225, O75417, P19821, P30313, P35207, P46835, P52027, P52028, P56105, P74933, P80194, Q09475, Q54XN7, Q5H9U9, Q8CGS6, Q8IY21, Q9P7T8, Q9RAA9, Q9S1G2, Q9V0A9, A2PYH4, A2RUV5, A3MSA1, A7IB61, A8MB76, D0KN27, D3Z4R1, E1BNG3, E7F8F4, E9PZJ8, F1LNJ2, F1LPQ2, F1NTD6, F4JAA5, O48534, O59025

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
MDM2	“down-regulates quantity by destabilization”	POLQ	polyubiquitination
MDM2	“down-regulates quantity by destabilization”	POLQ	ubiquitination

Disease & clinical

Clinical variants and AI predictions

ClinVar

3601 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	2393
Likely benign	1136
Benign	33

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

17093 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:121496920:A:C	S722R	0.998
3:121496920:A:T	S722R	0.998
3:121496922:T:G	S722R	0.998
3:121509616:A:G	L635P	0.998
3:121533155:A:C	S265R	0.998
3:121533155:A:T	S265R	0.998
3:121533157:T:G	S265R	0.998
3:121544733:A:C	Y113D	0.998
3:121544735:A:T	V112D	0.998
3:121544787:A:G	W95R	0.998
3:121544787:A:T	W95R	0.998
3:121512022:A:C	S492R	0.997
3:121512022:A:T	S492R	0.997
3:121512024:T:G	S492R	0.997
3:121520080:A:G	L420P	0.997
3:121537190:T:A	E217V	0.997
3:121541385:A:C	F146L	0.997
3:121541385:A:T	F146L	0.997
3:121541387:A:G	F146L	0.997
3:121541469:A:C	S118R	0.997
3:121541469:A:T	S118R	0.997
3:121541471:T:G	S118R	0.997
3:121541479:G:T	A115D	0.997
3:121432333:A:G	W2582R	0.996
3:121432333:A:T	W2582R	0.996
3:121493689:A:G	W771R	0.996
3:121493689:A:T	W771R	0.996
3:121496912:A:G	L725P	0.996
3:121510089:A:G	L589P	0.996
3:121519972:C:G	R456P	0.996

dbSNP variants (sampled 300 via entrez): RS1000057040 (3:121459820 T>C), RS1000063003 (3:121475694 C>T), RS1000083308 (3:121443157 AT>A), RS1000094340 (3:121522576 G>A), RS1000127403 (3:121447298 G>C), RS1000127712 (3:121433289 C>T), RS1000161152 (3:121495818 C>A,T), RS1000175171 (3:121450080 G>A,C), RS1000180306 (3:121542734 T>A), RS1000195330 (3:121482671 A>G,T), RS1000210901 (3:121478268 AT>A), RS1000247731 (3:121482397 G>A,C), RS1000268401 (3:121449869 G>A,T), RS1000284210 (3:121460107 C>T), RS1000290932 (3:121483159 G>A,C)

Disease associations

OMIM: gene MIM:604419 | disease phenotypes:

GenCC curated gene-disease

Mondo (2): teratoma (MONDO:0002601), hereditary breast ovarian cancer syndrome (MONDO:0003582)

Orphanet (1): Hereditary breast and/or ovarian cancer syndrome (Orphanet:145)

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST001767_4	Aging (facial)	1.000000e-09
GCST011379_4	Cutaneous mastocytosis (childhood)	3.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0022597	aging

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D061325	Hereditary Breast and Ovarian Cancer Syndrome	C04.588.180.483; C04.588.322.455.431; C04.700.517; C12.050.351.500.056.630.705.431; C12.050.351.937.418.685.431; C12.100.250.056.630.705.431; C12.900.418.685.431; C16.320.700.517; C17.800.090.500.483; C19.344.410.431; C19.391.630.705.431
D013724	Teratoma	C04.557.465.910

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6025 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 11,401 (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
CHEMBL36506	NOVOBIOCIN	4	11,401

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — DNA polymerases

Most potent curated ligand interactions (5 total), top 5:

Ligand	Action	Affinity	Parameter
RP-2119	Inhibition	9.15	pIC50
SY-589	Inhibition	8.64	pIC50
RP-6685	Inhibition	8.24	pIC50
ART812	Inhibition	8.12	pIC50
ART558	Inhibition	8.1	pIC50

Binding affinities (BindingDB)

250 measured of 342 human assays (837 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
2-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-1-((4-chloropyridin-2-yl)methyl)-4-(1-methylcyclopropoxy)-1H-benzo[d]imidazole	IC50	2 nM	US-20250195530: POLQ INHIBITORS
2-(2-Chloro-4-(2-(4-methylpiperazin-1-yl)ethoxy)phenyl)-1-(3-chlorobenzyl)-5-isopropoxy-1H-benzo[d]imidazole	IC50	2 nM	US-20250195530: POLQ INHIBITORS
3-(4-(1-Benzyl-5-isopropoxy-1H-benzo[d]imidazol-2-yl)-3-chlorophenoxy)propan-1-amine	IC50	2 nM	US-20250195530: POLQ INHIBITORS
9-Benzyl-8-(2-chloro-4-((1-methylpiperidin-4-yl)methoxy)phenyl)-6-(1-methylcyclopropoxy)-9H-purine	IC50	2 nM	US-20250195530: POLQ INHIBITORS
1-benzyl-2-(2- chloro-4-((1- methylazepan-4- yl)oxy)phenyl)- 5-isopropoxy- 1H- benzo[d]imidazole (Isomer 1)	IC50	2 nM	US-20250195530: POLQ INHIBITORS
1-benzyl-2-(2- chloro-4-((1- methylazepan-4- yl)oxy)phenyl)- 5-isopropoxy- 1H- benzo[d]imidazole (Isomer 2)	IC50	2 nM	US-20250195530: POLQ INHIBITORS
N-(3-(4-(1-benzyl- 5-isopropoxy-1H- benzo[d]imidazol- 2-yl)-3- chlorophenoxy) propyl)acetamide	IC50	2 nM	US-20250195530: POLQ INHIBITORS
1-(3- chlorobenzyl)-5- isopropoxy-2-(4- methyl-6-(2-(4- methylpiperazin-1- yl)ethoxy)pyridin- 3-yl)-1H- benzo[d]imidazole	IC50	2 nM	US-20250195530: POLQ INHIBITORS
1-benzyl-2-(2- chloro-4-(2-(1- methylpyrrolidin-2- yl)ethoxy)phenyl)-5- isopropoxy-1H- benzo[d]imidazole (Isomer 1)	IC50	2 nM	US-20250195530: POLQ INHIBITORS
9-benzyl-6- isopropoxy- 8-(2- methyl-4- (2- (piperazin- 1-yl) ethoxy) phenyl)- 9H-purine	IC50	2 nM	US-20250195530: POLQ INHIBITORS
9-benzyl-8-(2-chloro-3- methoxyphenyl)-6-(1- methylcyclopropoxy)-9H- purine	IC50	2 nM	US-20250195530: POLQ INHIBITORS
1-(4-((4- (9-benzyl-6-(1- methylcyclo- propoxy)-9H- purin-8-yl)-3- chlorophenoxy) methyl)piperidin- 1-yl)ethan-1-one	IC50	2 nM	US-20250195530: POLQ INHIBITORS
9-benzyl-8-(2- chloro-3-(2- (piperazin-1- yl)ethoxy) phenyl)-6-(1- methylcyclo- propoxy)-9H- purine	IC50	2 nM	US-20250195530: POLQ INHIBITORS
9-benzyl-8-(2- chloro-3-(2-(4- methyl- piperazin-1- yl)ethoxy) phenyl)-6-(1- methylcyclo- propoxy)-9H- purine	IC50	2 nM	US-20250195530: POLQ INHIBITORS
9-benzyl-8-(2- chloro-4-((1- methylazepan-4- yl)oxy)phenyl)- 6-(1- methylcyclo- propoxy)-9H- purine (Isomer 2)	IC50	2 nM	US-20250195530: POLQ INHIBITORS
9-benzyl-8-(2- chloro-4-(2-(1- methyl- pyrrolidin-2- yl)ethoxy) phenyl)-6-(1- methylcyclo- propoxy)-9H- purine	IC50	2 nM	US-20250195530: POLQ INHIBITORS
1-(4-(2-(4-(9- benzyl-6-(1- methylcyclo- propoxy)-9H- purin-8-yl)-3- chlorophenoxy) ethyl)piperazin- 1-yl)ethan-1-one	IC50	2 nM	US-20250195530: POLQ INHIBITORS
1-(4-(2-(3-(9- benzyl-6-(1- methylcyclo- propoxy)-9H- purin-8-yl)-2- chlorophenoxy) ethyl)piperazin- 1-yl)ethan-1-one	IC50	2 nM	US-20250195530: POLQ INHIBITORS
1-(4-(3-((5-(9- benzyl-6-(1- methylcyclopropoxy)- 9H-purin-8- yl)-4- methylpyridin-2- yl)oxy)propyl) piperazin-1- yl)ethan-1-one	IC50	2 nM	US-20250195530: POLQ INHIBITORS
1-(4-(2-((5-(9- benzyl-6-(1- methylcyclopropoxy)- 9H-purin-8- yl)-4- methylpyridin-2- yl)oxy)ethyl) piperazin-1-yl)ethan- 1-one	IC50	2 nM	US-20250195530: POLQ INHIBITORS
1-(3-(4-(9- benzyl-6-(1- methyl- cyclopropoxy)- 9H- purin-8-yl)-3- chlorophenoxy) propyl)azetidin- 3-ol	IC50	2 nM	US-20250195530: POLQ INHIBITORS
9-benzyl-8-(2- fluoro-4-(2-(4- methylpiperazin- 1- yl)ethoxy)phenyl)- 6-(1- methyl- cyclopropoxy)- 9H- purine	IC50	2 nM	US-20250195530: POLQ INHIBITORS
(R)-4-(2-(4-(9- benzyl-6-(1- methyl- cyclopropoxy)- 9H- purin-8-yl)-3- chlorophenoxy) ethyl)-3- methylpiperazin- 2- one	IC50	2 nM	US-20250195530: POLQ INHIBITORS
9-benzyl-8-(2,6- dimethyl-4-(2- (4- methylpiperazin- 1- yl)ethoxy) phenyl)- 6-(1- methyl- cyclopropoxy)- 9H-purine	IC50	2 nM	US-20250195530: POLQ INHIBITORS
9-benzyl-8-(2- bromo-4-(2-(4- methylpiperazin-1- yl)ethoxy)phenyl)- 6-(1- methyl- cyclopropoxy)- 9H-purine	IC50	2 nM	US-20250195530: POLQ INHIBITORS
(R)-8-(2-chloro- 4-(2-(piperazin-1- yl)ethoxy)phenyl)- 6-(1- methylcyclopropoxy)- 9-(2-phenylpropyl)- 9H-purine	IC50	2 nM	US-20250195530: POLQ INHIBITORS
8-(2-chloro-4-(2- (piperazin-1- yl)ethoxy)phenyl)- 6-(1- methylcyclopropoxy)- 9- phenethyl-9H- purine	IC50	2 nM	US-20250195530: POLQ INHIBITORS
9-(3- chlorobenzyl)-8- (4-methyl-6-(2- (piperazin-1- yl)ethoxy)pyridin- 3-yl)-6-(1- methylcyclopropoxy)- 9H-purine	IC50	2 nM	US-20250195530: POLQ INHIBITORS
8-(2-chloro-4-(2- (piperazin-1- yl)ethoxy)phenyl)- 6-(1- methylcyclopropoxy)- 9-((4- (trifluoromethyl) pyridin-2- yl)methyl)-9H- purine	IC50	2 nM	US-20250195530: POLQ INHIBITORS
2-((8-(2-chloro-4- (2-(piperazin-1- yl)ethoxy)phenyl)- 6-(1-methyl- cyclopropoxy)- 9H-purin-9- yl)methyl)iso- nicotinonitrile	IC50	2 nM	US-20250195530: POLQ INHIBITORS
8-(2-chloro-4-(2- (piperazin-1- yl)ethoxy) phenyl)-9-(3- chlorobenzyl)-6- cyclopropoxy- 9H-purine	IC50	2 nM	US-20250195530: POLQ INHIBITORS
(S)-9-benzyl-8- (2-chloro-4-(2- (2- methylpiperazin- 1-yl) ethoxy)phenyl)- 6-(1-methyl- cyclopropoxy)- 9H-purine	IC50	2 nM	US-20250195530: POLQ INHIBITORS
(R)-9-benzyl-8- (2-chloro-4-(2- (2- methylpiperazin- 1-yl) ethoxy)phenyl)- 6-(1-methyl- cyclopropoxy)- 9H-purine	IC50	2 nM	US-20250195530: POLQ INHIBITORS
1-(2-(4-(9- benzyl-6-(1- methylcyclo- propoxy)-9H- purin-8-yl)-3- chlorophenoxy) ethyl)-1,4- diazepan-2-one	IC50	2 nM	US-20250195530: POLQ INHIBITORS
1-(2-(4-(9- benzyl-6-(1- methylcyclo- propoxy)- 9H-purin-8- yl)-3- chlorophenoxy) ethyl)-3- methylpiperazin- 2-one (Isomer 2)	IC50	2 nM	US-20250195530: POLQ INHIBITORS
6-(2-(4-(9- benzyl-6-(1- methylcyclo- propoxy)- 9H-purin-8- yl)-3- chlorophenoxy) ethyl)-3,6- diazabicyclo [3.1.1]heptane	IC50	2 nM	US-20250195530: POLQ INHIBITORS
1-(2-(4-(9- benzyl-6-(1- methylcyclo- propoxy)- 9H-purin-8- yl)-3- chlorophenoxy) ethyl)-3,3- dimethyl- piperazin- 2-one	IC50	2 nM	US-20250195530: POLQ INHIBITORS
8-(4-(2-(4,7- diazaspiro [2.5]octan-7- yl)ethoxy)-2- chlorophenyl)-9- benzyl-6-(1- methylcyclo- propoxy)- 9H-purine	IC50	2 nM	US-20250195530: POLQ INHIBITORS
(R)-(4-(2-(4-(9- benzyl-6-(1- methylcyclo- propoxy)- 9H-purin-8- yl)-3- chlorophenoxy) ethyl)piperazin- 2-yl)methanol	IC50	2 nM	US-20250195530: POLQ INHIBITORS
8-(4-(2-((1S,4S)- 2,5- diazabicyclo [2.2.1]heptan-2- yl)ethoxy)-2- chlorophenyl)-9- benzyl-6-(1- methylcyclo- propoxy)- 9H-purine	IC50	2 nM	US-20250195530: POLQ INHIBITORS
8-(4-(2-((1R,4R)- 2,5- diazabicyclo [2.2.1]heptan-2- yl)ethoxy)-2- chlorophenyl)-9- benzyl-6-(1- methylcyclo- propoxy)- 9H-purine	IC50	2 nM	US-20250195530: POLQ INHIBITORS
(1S,4S)-2-(2-(4- (9-benzyl-6-(1- methylcyclo- propoxy)-9H- purin-8-yl)-3- chlorophenoxy) ethyl)-2,5- diazabicyclo [2.2.2]octane	IC50	2 nM	US-20250195530: POLQ INHIBITORS
8-(2-chloro-4-(2- (piperazin-1- yl)ethoxy)phenyl)- 9-((4-cyclo- propylpyridin- 2-yl)methyl)-6- (1-methyl- cyclopropoxy)- 9H-purine	IC50	2 nM	US-20250195530: POLQ INHIBITORS
8-(2-chloro-4-(2- (piperazin-1- yl)ethoxy)phenyl)- 9-((4-ethylpyridin- 2-yl)methyl)-6-(1- methylcyclo- propoxy)- 9H-purine	IC50	2 nM	US-20250195530: POLQ INHIBITORS
9-Benzyl-6-isopropoxy-8-(2-methyl-4-(2-(4-methylpiperazin-1-yl)ethoxy)phenyl)-9H-purine	IC50	2.51 nM	US-20250195530: POLQ INHIBITORS
9-Benzyl-8-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-6-((1,1,1-trifluoro-2-methylpropan-2-yl)oxy)-9H-purine	IC50	2.51 nM	US-20250195530: POLQ INHIBITORS
2-(2-Chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-3-((4-chloropyridin-2-yl)methyl)-7-(1-methylcyclopropoxy)-3H-imidazo[4,5-b]pyridine	IC50	2.51 nM	US-20250195530: POLQ INHIBITORS
2-(2-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-1-((4-chloropyridin-2-yl)methyl)-4-(1-methylcyclopropoxy)-1H-imidazo[4,5-c]pyridine	IC50	2.51 nM	US-20250195530: POLQ INHIBITORS
1-(4-(2- (4-(9- benzyl-6- isopropoxy- 9H-purin- 8-yl)-3- methyl- phenoxy) ethyl) piperazin-1- yl)ethan-1- one	IC50	2.51 nM	US-20250195530: POLQ INHIBITORS
9-benzyl-8-(2-methyl-4- (2-(4-methylpiperazin-1- yl)ethoxy)phenyl)-6-(1- methylcyclopropoxy)-9H- purine	IC50	2.51 nM	US-20250195530: POLQ INHIBITORS

ChEMBL bioactivities

360 potent at pChembl≥5 of 367 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.17	IC50	0.068	nM	CHEMBL5204203
9.70	IC50	0.2	nM	CHEMBL5175156
9.40	IC50	0.4	nM	CHEMBL5206022
9.29	IC50	0.51	nM	CHEMBL5197367
9.26	IC50	0.55	nM	CHEMBL5187422
9.14	IC50	0.72	nM	CHEMBL5174509
9.12	IC50	0.75	nM	CHEMBL5197173
9.09	IC50	0.82	nM	CHEMBL5170373
9.04	IC50	0.91	nM	CHEMBL5194637
9.00	IC50	0.99	nM	CHEMBL5197021
8.92	IC50	1.2	nM	CHEMBL5187337
8.85	IC50	1.4	nM	CHEMBL5188048
8.80	IC50	1.6	nM	CHEMBL5181369
8.77	IC50	1.7	nM	CHEMBL5174376
8.70	IC50	2	nM	CHEMBL5429065
8.68	IC50	2.1	nM	CHEMBL5200250
8.62	IC50	2.4	nM	CHEMBL5566472
8.60	IC50	2.5	nM	CHEMBL5174283
8.54	IC50	2.9	nM	CHEMBL5195161
8.41	IC50	3.9	nM	CHEMBL5194194
8.39	IC50	4.1	nM	CHEMBL5208956
8.38	IC50	4.2	nM	CHEMBL5206029
8.32	Kd	4.8	nM	CHEMBL5206992
8.31	IC50	4.9	nM	CHEMBL5202450
8.30	IC50	5	nM	CHEMBL5418074
8.30	IC50	5.012	nM	CHEMBL6172090
8.27	IC50	5.4	nM	CHEMBL5205456
8.24	IC50	5.8	nM	CHEMBL5187422
8.24	IC50	5.8	nM	CHEMBL5591828
8.23	IC50	5.9	nM	CHEMBL5190089
8.19	Kd	6.4	nM	CHEMBL5206992
8.17	IC50	6.8	nM	CHEMBL5175531
8.15	IC50	7	nM	CHEMBL5176919
8.15	IC50	7	nM	CHEMBL5411191
8.13	IC50	7.49	nM	CHEMBL5195920
8.12	IC50	7.6	nM	CHEMBL5191330
8.10	IC50	7.9	nM	CHEMBL5206992
8.10	IC50	7.9	nM	CHEMBL5573055
8.10	IC50	7.943	nM	CHEMBL6134385
8.09	Kd	8.2	nM	CHEMBL5206829
8.07	IC50	8.479	nM	CHEMBL5195920
8.06	IC50	8.714	nM	CHEMBL5195920
8.06	IC50	8.8	nM	CHEMBL5180095
8.05	IC50	9	nM	CHEMBL5200171
8.03	IC50	9.4	nM	CHEMBL5200410
8.00	IC50	10	nM	CHEMBL5195920
8.00	IC50	10	nM	CHEMBL6163075
7.96	Kd	11	nM	CHEMBL5206829
7.95	IC50	11.13	nM	CHEMBL5195920
7.90	IC50	12.59	nM	CHEMBL6172559

PubChem BioAssay actives

153 with measured affinity, of 214 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
N-[4-(N-[2-[2,4-bis(trifluoromethyl)phenyl]acetyl]anilino)but-2-ynyl]-5-methyl-1,3,4-oxadiazole-2-carboxamide	1856651: Inhibition of human DNA polymerase theta pol domain (1819 to 2590 residues) expressed in Escherichia coli BL21 (DE3) cells preincubated for 15 mins followed by DNA and dNTP addition and measured after 120 mins by Picogreen dye fluorescence intensity analysis	ic50	0.0001	uM
N-[4-(N-[2-[2,4-bis(trifluoromethyl)phenyl]acetyl]anilino)but-2-ynyl]pyridine-3-carboxamide	1856651: Inhibition of human DNA polymerase theta pol domain (1819 to 2590 residues) expressed in Escherichia coli BL21 (DE3) cells preincubated for 15 mins followed by DNA and dNTP addition and measured after 120 mins by Picogreen dye fluorescence intensity analysis	ic50	0.0002	uM
N-[4-(N-[2-[2,4-bis(trifluoromethyl)phenyl]acetyl]anilino)but-2-ynyl]pyridine-2-carboxamide	1856651: Inhibition of human DNA polymerase theta pol domain (1819 to 2590 residues) expressed in Escherichia coli BL21 (DE3) cells preincubated for 15 mins followed by DNA and dNTP addition and measured after 120 mins by Picogreen dye fluorescence intensity analysis	ic50	0.0004	uM
2-[2,4-bis(trifluoromethyl)phenyl]-N-[3-(6-oxo-1H-pyridin-2-yl)prop-2-ynyl]-N-phenylacetamide	1856651: Inhibition of human DNA polymerase theta pol domain (1819 to 2590 residues) expressed in Escherichia coli BL21 (DE3) cells preincubated for 15 mins followed by DNA and dNTP addition and measured after 120 mins by Picogreen dye fluorescence intensity analysis	ic50	0.0005	uM
N-[3-(6-aminopyridazin-3-yl)prop-2-ynyl]-2-[3,5-bis(trifluoromethyl)-2-pyridinyl]-N-(4-fluorophenyl)acetamide	1856655: Inhibition of N-terminal His8-tagged/C-terminal FLAG-tagged full length human DNA polymerase theta ( 1 to 2590 residues) polymerase activity expressed in HEK2936E cells	ic50	0.0006	uM
2-[3,5-bis(trifluoromethyl)-2-pyridinyl]-N-(4-fluorophenyl)-N-[3-(5-pyrrolidin-3-yl-2-pyridinyl)prop-2-ynyl]acetamide	1856651: Inhibition of human DNA polymerase theta pol domain (1819 to 2590 residues) expressed in Escherichia coli BL21 (DE3) cells preincubated for 15 mins followed by DNA and dNTP addition and measured after 120 mins by Picogreen dye fluorescence intensity analysis	ic50	0.0007	uM
N-(4-acetamidobut-2-ynyl)-2-[2,4-bis(trifluoromethyl)phenyl]-N-phenylacetamide	1856651: Inhibition of human DNA polymerase theta pol domain (1819 to 2590 residues) expressed in Escherichia coli BL21 (DE3) cells preincubated for 15 mins followed by DNA and dNTP addition and measured after 120 mins by Picogreen dye fluorescence intensity analysis	ic50	0.0008	uM
N-[3-[1-(azetidin-3-yl)pyrazol-4-yl]prop-2-ynyl]-2-[3,5-bis(trifluoromethyl)-2-pyridinyl]-N-(4-fluorophenyl)acetamide	1856651: Inhibition of human DNA polymerase theta pol domain (1819 to 2590 residues) expressed in Escherichia coli BL21 (DE3) cells preincubated for 15 mins followed by DNA and dNTP addition and measured after 120 mins by Picogreen dye fluorescence intensity analysis	ic50	0.0008	uM
2-[3,5-bis(trifluoromethyl)-2-pyridinyl]-N-(4-fluorophenyl)-N-[3-[1-(methylsulfonylmethyl)pyrazol-4-yl]prop-2-ynyl]acetamide	1856651: Inhibition of human DNA polymerase theta pol domain (1819 to 2590 residues) expressed in Escherichia coli BL21 (DE3) cells preincubated for 15 mins followed by DNA and dNTP addition and measured after 120 mins by Picogreen dye fluorescence intensity analysis	ic50	0.0009	uM
2-[4-[3-(N-[2-[3,5-bis(trifluoromethyl)-2-pyridinyl]acetyl]-4-fluoroanilino)prop-1-ynyl]pyrazol-1-yl]propanamide	1856651: Inhibition of human DNA polymerase theta pol domain (1819 to 2590 residues) expressed in Escherichia coli BL21 (DE3) cells preincubated for 15 mins followed by DNA and dNTP addition and measured after 120 mins by Picogreen dye fluorescence intensity analysis	ic50	0.0010	uM
2-[2,4-bis(trifluoromethyl)phenyl]-N-[3-(3-methylimidazol-4-yl)prop-2-ynyl]-N-phenylacetamide	1856651: Inhibition of human DNA polymerase theta pol domain (1819 to 2590 residues) expressed in Escherichia coli BL21 (DE3) cells preincubated for 15 mins followed by DNA and dNTP addition and measured after 120 mins by Picogreen dye fluorescence intensity analysis	ic50	0.0012	uM
2-[2,4-bis(trifluoromethyl)phenyl]-N-phenyl-N-(3-pyridazin-3-ylprop-2-ynyl)acetamide	1856651: Inhibition of human DNA polymerase theta pol domain (1819 to 2590 residues) expressed in Escherichia coli BL21 (DE3) cells preincubated for 15 mins followed by DNA and dNTP addition and measured after 120 mins by Picogreen dye fluorescence intensity analysis	ic50	0.0014	uM
N-[3-(2-aminopyrimidin-5-yl)prop-2-ynyl]-2-[3,5-bis(trifluoromethyl)-2-pyridinyl]-N-(4-fluorophenyl)acetamide	1856651: Inhibition of human DNA polymerase theta pol domain (1819 to 2590 residues) expressed in Escherichia coli BL21 (DE3) cells preincubated for 15 mins followed by DNA and dNTP addition and measured after 120 mins by Picogreen dye fluorescence intensity analysis	ic50	0.0016	uM
N-[3-(3-amino-1-methylpyrazol-5-yl)prop-2-ynyl]-2-[3,5-bis(trifluoromethyl)-2-pyridinyl]-N-(4-fluorophenyl)acetamide	1856651: Inhibition of human DNA polymerase theta pol domain (1819 to 2590 residues) expressed in Escherichia coli BL21 (DE3) cells preincubated for 15 mins followed by DNA and dNTP addition and measured after 120 mins by Picogreen dye fluorescence intensity analysis	ic50	0.0017	uM
1-[6-[3-methyl-4-[(3-methyloxolan-3-yl)methoxy]phenyl]pyrazin-2-yl]-3-(6-methyl-3-pyridinyl)urea	1988497: Inhibition of N-terminal/C-termianl Flag-tagged POLQ (unknown origin) (2 to 2590 residues) expressed in baculovirus incubated for 30 mins by fluorescence based analysis	ic50	0.0020	uM
2-[3,5-bis(trifluoromethyl)-2-pyridinyl]-N-(4-fluorophenyl)-N-[3-(2-methoxypyrimidin-5-yl)prop-2-ynyl]acetamide	1856651: Inhibition of human DNA polymerase theta pol domain (1819 to 2590 residues) expressed in Escherichia coli BL21 (DE3) cells preincubated for 15 mins followed by DNA and dNTP addition and measured after 120 mins by Picogreen dye fluorescence intensity analysis	ic50	0.0021	uM
N-[5-[(4-chlorophenyl)methoxy]-1,3,4-thiadiazol-2-yl]-3-(2-methoxyphenyl)pyridine-4-carboxamide	2080474: Inhibition of human DNA polymerase theta (67 to 970 residues) ATPase activity expressed in Sf9 insect cells incubated for 40 mins by ADP-glo assay	ic50	0.0024	uM
2-[2,4-bis(trifluoromethyl)phenyl]-N-phenyl-N-(3-pyridin-3-ylprop-2-ynyl)acetamide	1856651: Inhibition of human DNA polymerase theta pol domain (1819 to 2590 residues) expressed in Escherichia coli BL21 (DE3) cells preincubated for 15 mins followed by DNA and dNTP addition and measured after 120 mins by Picogreen dye fluorescence intensity analysis	ic50	0.0025	uM
2-[2,4-bis(trifluoromethyl)phenyl]-N-phenyl-N-(3-pyridin-2-ylprop-2-ynyl)acetamide	1856651: Inhibition of human DNA polymerase theta pol domain (1819 to 2590 residues) expressed in Escherichia coli BL21 (DE3) cells preincubated for 15 mins followed by DNA and dNTP addition and measured after 120 mins by Picogreen dye fluorescence intensity analysis	ic50	0.0029	uM
2-[2,4-bis(trifluoromethyl)phenyl]-N-phenyl-N-(3-pyrimidin-2-ylprop-2-ynyl)acetamide	1856651: Inhibition of human DNA polymerase theta pol domain (1819 to 2590 residues) expressed in Escherichia coli BL21 (DE3) cells preincubated for 15 mins followed by DNA and dNTP addition and measured after 120 mins by Picogreen dye fluorescence intensity analysis	ic50	0.0039	uM
(4S)-N-(2,4-difluoro-3-methylphenyl)-N-methyl-3-[6-methyl-4-(trifluoromethyl)-2-pyridinyl]-2-oxo-1,3-oxazolidine-4-carboxamide	1857356: Inhibition of recombinant human full length DNA polymerase theta using DNA substrate measured after 1 hrs in presence of dNTPs by plate reader assay	ic50	0.0041	uM
N-[3-(5-aminopyrazin-2-yl)prop-2-ynyl]-2-[3,5-bis(trifluoromethyl)-2-pyridinyl]-N-(4-fluorophenyl)acetamide	1856651: Inhibition of human DNA polymerase theta pol domain (1819 to 2590 residues) expressed in Escherichia coli BL21 (DE3) cells preincubated for 15 mins followed by DNA and dNTP addition and measured after 120 mins by Picogreen dye fluorescence intensity analysis	ic50	0.0042	uM
(2S,3R)-1-[3-cyano-6-methyl-4-(trifluoromethyl)-2-pyridinyl]-3-hydroxy-N-methyl-N-(3-methylphenyl)pyrrolidine-2-carboxamide	1857358: Displacement of tracer from recombinant Tb-labeled DNA polymerase theta (unknown origin) using DNA as substrate preincubated for 30 mins followed by compound addition for 2 hrs by HTRF assay	kd	0.0048	uM
2-[3,5-bis(trifluoromethyl)-2-pyridinyl]-N-(4-fluorophenyl)-N-[3-(6-methoxypyridazin-3-yl)prop-2-ynyl]acetamide	1856651: Inhibition of human DNA polymerase theta pol domain (1819 to 2590 residues) expressed in Escherichia coli BL21 (DE3) cells preincubated for 15 mins followed by DNA and dNTP addition and measured after 120 mins by Picogreen dye fluorescence intensity analysis	ic50	0.0049	uM
(4R)-4-[4-chloro-1-(3-chloro-4-fluorophenyl)imidazol-2-yl]-3-[6-methyl-4-(trifluoromethyl)-2-pyridinyl]-1,3-oxazolidin-2-one	1988499: Inhibition of POLQ PD (unknown origin) (1819 to 2590 residues) incubated for 15 mins by fluorescence based analysis	ic50	0.0050	uM
(4S)-N-(3-chloro-2,4-difluorophenyl)-N-methyl-3-[6-methyl-4-(trifluoromethyl)-2-pyridinyl]-2-oxo-1,3-oxazolidine-4-carboxamide	1857356: Inhibition of recombinant human full length DNA polymerase theta using DNA substrate measured after 1 hrs in presence of dNTPs by plate reader assay	ic50	0.0054	uM
N-[3-(6-aminopyridazin-3-yl)prop-2-ynyl]-N-(4-fluorophenyl)-2-[6-methyl-4-(trifluoromethyl)-2-pyridinyl]acetamide	2107386: Inhibition of DNA polymerase theta (unknown origin) using 5-TAMRA-CCTTCCTCCCGTGTCTTGTACCTTCCCGTCAGGAGGAAGG-BHQ-3’ as substrate incubated for 60 mins by fluorescence analysis	ic50	0.0058	uM
(2S,3R)-N-(3-chloro-4-fluorophenyl)-3-hydroxy-N-methyl-1-[6-methyl-4-(trifluoromethyl)-2-pyridinyl]-5-oxopyrrolidine-2-carboxamide	1857356: Inhibition of recombinant human full length DNA polymerase theta using DNA substrate measured after 1 hrs in presence of dNTPs by plate reader assay	ic50	0.0059	uM
(2S)-N-methyl-N-(3-methylphenyl)-1-[6-methyl-4-(trifluoromethyl)-2-pyridinyl]-5-oxopyrrolidine-2-carboxamide	1857356: Inhibition of recombinant human full length DNA polymerase theta using DNA substrate measured after 1 hrs in presence of dNTPs by plate reader assay	ic50	0.0068	uM
1-[2-[3-methyl-4-[[(3R)-3-methyloxolan-3-yl]methoxy]phenyl]-1,3-thiazol-4-yl]-3-[(3S)-piperidin-3-yl]urea	1988497: Inhibition of N-terminal/C-termianl Flag-tagged POLQ (unknown origin) (2 to 2590 residues) expressed in baculovirus incubated for 30 mins by fluorescence based analysis	ic50	0.0070	uM
(4S)-N-methyl-N-(3-methylphenyl)-3-[6-methyl-4-(trifluoromethyl)-2-pyridinyl]-2-oxo-1,3-oxazolidine-4-carboxamide	1857356: Inhibition of recombinant human full length DNA polymerase theta using DNA substrate measured after 1 hrs in presence of dNTPs by plate reader assay	ic50	0.0070	uM
N-methyl-N-phenyl-2-[3-(trifluoromethyl)-5,6-dihydro-4H-cyclopenta[c]pyrazol-2-yl]ethanethioamide	1856691: Inhibition of human DNA polymerase theta using DNA 16/19 as substrate at 1 nM of enzyme concentration	ic50	0.0075	uM
(2S,3S,4S)-N-(3-chloro-4-fluorophenyl)-3,4-dihydroxy-N-methyl-1-[6-methyl-4-(trifluoromethyl)-2-pyridinyl]-5-oxopyrrolidine-2-carboxamide	1857356: Inhibition of recombinant human full length DNA polymerase theta using DNA substrate measured after 1 hrs in presence of dNTPs by plate reader assay	ic50	0.0076	uM
(2S,3R)-N-(3-chloro-4-fluorophenyl)-1-[3-cyano-6-methyl-4-(trifluoromethyl)-2-pyridinyl]-3-hydroxy-N-methylpyrrolidine-2-carboxamide	2107386: Inhibition of DNA polymerase theta (unknown origin) using 5-TAMRA-CCTTCCTCCCGTGTCTTGTACCTTCCCGTCAGGAGGAAGG-BHQ-3’ as substrate incubated for 60 mins by fluorescence analysis	ic50	0.0079	uM
(2S,4S)-1-[3-cyano-6-methyl-4-(trifluoromethyl)-2-pyridinyl]-4-hydroxy-N-methyl-N-(3-methylphenyl)pyrrolidine-2-carboxamide	1857358: Displacement of tracer from recombinant Tb-labeled DNA polymerase theta (unknown origin) using DNA as substrate preincubated for 30 mins followed by compound addition for 2 hrs by HTRF assay	kd	0.0082	uM
(2S)-1-[3-cyano-6-methyl-4-(trifluoromethyl)-2-pyridinyl]-N-(3-methylphenyl)-N-propan-2-ylpyrrolidine-2-carboxamide	1857356: Inhibition of recombinant human full length DNA polymerase theta using DNA substrate measured after 1 hrs in presence of dNTPs by plate reader assay	ic50	0.0088	uM
2-[3,5-bis(trifluoromethyl)-2-pyridinyl]-N-(4-fluorophenyl)-N-[3-(1-methylimidazol-4-yl)prop-2-ynyl]acetamide	1856651: Inhibition of human DNA polymerase theta pol domain (1819 to 2590 residues) expressed in Escherichia coli BL21 (DE3) cells preincubated for 15 mins followed by DNA and dNTP addition and measured after 120 mins by Picogreen dye fluorescence intensity analysis	ic50	0.0090	uM
(4S)-N-(4-fluoro-3-methylphenyl)-N-methyl-3-[6-methyl-4-(trifluoromethyl)-2-pyridinyl]-2-oxo-1,3-oxazolidine-4-carboxamide	1857356: Inhibition of recombinant human full length DNA polymerase theta using DNA substrate measured after 1 hrs in presence of dNTPs by plate reader assay	ic50	0.0094	uM
2-[2,4-bis(trifluoromethyl)phenyl]-N-phenyl-N-prop-2-ynylacetamide	1856651: Inhibition of human DNA polymerase theta pol domain (1819 to 2590 residues) expressed in Escherichia coli BL21 (DE3) cells preincubated for 15 mins followed by DNA and dNTP addition and measured after 120 mins by Picogreen dye fluorescence intensity analysis	ic50	0.0140	uM
2-[2,4-bis(trifluoromethyl)phenyl]-N-methyl-N-phenylacetamide	1856651: Inhibition of human DNA polymerase theta pol domain (1819 to 2590 residues) expressed in Escherichia coli BL21 (DE3) cells preincubated for 15 mins followed by DNA and dNTP addition and measured after 120 mins by Picogreen dye fluorescence intensity analysis	ic50	0.0140	uM
(4S)-N-(3-chloro-4-fluorophenyl)-N-methyl-3-[6-methyl-4-(trifluoromethyl)-2-pyridinyl]-2-oxo-1,3-oxazolidine-4-carboxamide	1857356: Inhibition of recombinant human full length DNA polymerase theta using DNA substrate measured after 1 hrs in presence of dNTPs by plate reader assay	ic50	0.0150	uM
(4S)-N-(3-chlorophenyl)-N-methyl-3-[6-methyl-4-(trifluoromethyl)-2-pyridinyl]-2-oxo-1,3-oxazolidine-4-carboxamide	1857356: Inhibition of recombinant human full length DNA polymerase theta using DNA substrate measured after 1 hrs in presence of dNTPs by plate reader assay	ic50	0.0150	uM
(4S)-N-(3-chloro-2-fluorophenyl)-N-methyl-3-[6-methyl-4-(trifluoromethyl)-2-pyridinyl]-2-oxo-1,3-oxazolidine-4-carboxamide	1857356: Inhibition of recombinant human full length DNA polymerase theta using DNA substrate measured after 1 hrs in presence of dNTPs by plate reader assay	ic50	0.0150	uM
(2S,4S)-N-(3-chloro-4-fluorophenyl)-1-[3-cyano-6-methyl-4-(trifluoromethyl)-2-pyridinyl]-4-hydroxy-N-methylpyrrolidine-2-carboxamide	1988499: Inhibition of POLQ PD (unknown origin) (1819 to 2590 residues) incubated for 15 mins by fluorescence based analysis	ic50	0.0160	uM
2-[2,4-bis(trifluoromethyl)phenyl]-N-(4-fluorophenyl)-N-methylacetamide	1856651: Inhibition of human DNA polymerase theta pol domain (1819 to 2590 residues) expressed in Escherichia coli BL21 (DE3) cells preincubated for 15 mins followed by DNA and dNTP addition and measured after 120 mins by Picogreen dye fluorescence intensity analysis	ic50	0.0170	uM
2-[2,4-bis(trifluoromethyl)phenyl]-N-(4-fluorophenyl)-N-(trideuteriomethyl)acetamide	1856651: Inhibition of human DNA polymerase theta pol domain (1819 to 2590 residues) expressed in Escherichia coli BL21 (DE3) cells preincubated for 15 mins followed by DNA and dNTP addition and measured after 120 mins by Picogreen dye fluorescence intensity analysis	ic50	0.0190	uM
(2S,4S)-1-(3-cyano-4,6-dimethyl-2-pyridinyl)-4-hydroxy-N-methyl-N-(3-methylphenyl)pyrrolidine-2-carboxamide	1857358: Displacement of tracer from recombinant Tb-labeled DNA polymerase theta (unknown origin) using DNA as substrate preincubated for 30 mins followed by compound addition for 2 hrs by HTRF assay	kd	0.0190	uM
(2S,3S,4S)-N-(3-chloro-4-fluorophenyl)-N-ethyl-3,4-dihydroxy-1-[6-methyl-4-(trifluoromethyl)-2-pyridinyl]-5-oxopyrrolidine-2-carboxamide	1857356: Inhibition of recombinant human full length DNA polymerase theta using DNA substrate measured after 1 hrs in presence of dNTPs by plate reader assay	ic50	0.0200	uM
(2S,3S,4S)-N-(5-chloro-2,4-difluorophenyl)-3,4-dihydroxy-1-[6-methyl-4-(trifluoromethyl)-2-pyridinyl]-5-oxo-N-(trideuteriomethyl)pyrrolidine-2-carboxamide	2107386: Inhibition of DNA polymerase theta (unknown origin) using 5-TAMRA-CCTTCCTCCCGTGTCTTGTACCTTCCCGTCAGGAGGAAGG-BHQ-3’ as substrate incubated for 60 mins by fluorescence analysis	ic50	0.0210	uM
(2S,3R)-N-(3-chloro-4-fluorophenyl)-1-[3-cyano-6-methyl-4-(trifluoromethyl)-2-pyridinyl]-3-(hydroxymethyl)-N-methylazetidine-2-carboxamide	2107386: Inhibition of DNA polymerase theta (unknown origin) using 5-TAMRA-CCTTCCTCCCGTGTCTTGTACCTTCCCGTCAGGAGGAAGG-BHQ-3’ as substrate incubated for 60 mins by fluorescence analysis	ic50	0.0215	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects expression, decreases expression	3
Valproic Acid	affects cotreatment, increases expression	3
Acetaminophen	decreases expression, increases expression	2
Benzo(a)pyrene	affects methylation, increases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
afuresertib	decreases expression	1
lasiocarpine	increases expression	1
triphenyl phosphate	affects expression	1
2,2’-methylenebis(4-methyl-6-tert-butylphenol)	affects response to substance, affects expression	1
N(4)-hydroxycytidine	increases expression	1
trichostatin A	increases expression	1
arsenite	affects binding, decreases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cypermethrin	decreases expression	1
perfluorooctanoic acid	decreases expression	1
manganese chloride	decreases expression, increases abundance	1
aflatoxin B2	decreases methylation	1
CGP 52608	increases reaction, affects binding	1
CPG-oligonucleotide	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
ICG 001	decreases expression	1
trans-10,cis-12-conjugated linoleic acid	decreases expression	1
dorsomorphin	increases expression, affects cotreatment	1
jinfukang	increases expression	1
incobotulinumtoxinA	decreases expression	1
PCI 5002	affects cotreatment, increases expression	1
Dasatinib	decreases expression	1
Sunitinib	decreases expression	1
Troglitazone	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1

ChEMBL screening assays

46 unique, capped per target: 46 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5111529	Binding	Inhibition of human DNA polymerase theta pol domain (1819 to 2590 residues) expressed in Escherichia coli BL21 (DE3) cells preincubated for 15 mins followed by DNA and dNTP addition and measured after 120 mins by Picogreen dye fluorescence	Identification of RP-6685, an Orally Bioavailable Compound that Inhibits the DNA Polymerase Activity of Polθ. — J Med Chem

Cellosaurus cell lines

6 cell lines: 5 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B8MR	Abcam HCT 116 POLQ KO	Cancer cell line	Male
CVCL_B9AF	Abcam MCF-7 POLQ KO	Cancer cell line	Female
CVCL_B9Q0	Abcam A-549 POLQ KO	Cancer cell line	Male
CVCL_D9NY	Ubigene HEK293 POLQ KO	Transformed cell line	Female
CVCL_TF12	HAP1 POLQ (-) 1	Cancer cell line	Male
CVCL_TF13	HAP1 POLQ (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02562170	PHASE4	COMPLETED	Protexa® Versus TiLoopBra® in Immediate Breast Reconstruction- A Pilot Study
NCT00104676	PHASE3	COMPLETED	Combination Chemotherapy in Treating Patients With Stage II or Stage III Germ Cell Tumors
NCT02375204	PHASE3	ACTIVE_NOT_RECRUITING	Standard-Dose Combination Chemotherapy or High-Dose Combination Chemotherapy and Stem Cell Transplant in Treating Patients with Relapsed or Refractory Germ Cell Tumors
NCT00673335	PHASE3	COMPLETED	Letrozole in Preventing Breast Cancer in Postmenopausal Women With a BRCA1 or BRCA2 Mutation
NCT00685256	PHASE3	COMPLETED	Standard Genetic Counseling With or Without a Decision Guide in Improving Communication Between Mothers Undergoing BRCA1/2 Testing and Their Minor-Age Children
NCT03162276	PHASE3	UNKNOWN	Trial of Inquiry Based Stress Reduction (IBSR) Program for BRCA1/2 Mutation Carriers
NCT00002931	PHASE2	COMPLETED	Combination Chemotherapy Plus Peripheral Stem Cell Transplantation in Treating Patients With Relapsed Germ Cell Cancer
NCT00301782	PHASE2	COMPLETED	Combination Chemotherapy in Treating Male Patients With Germ Cell Tumors
NCT00432094	PHASE2	COMPLETED	Autologous Peripheral Blood Stem Cell Transplant for Germ Cell Tumors
NCT00453232	PHASE2	COMPLETED	Combination Chemotherapy and Pegfilgrastim in Treating Men With Metastatic Germ Cell Tumors
NCT00453310	PHASE2	COMPLETED	Sunitinib in Treating Patients With Metastatic Germ Cell Tumors That Have Relapsed or Not Responded to Treatment
NCT00470366	PHASE2	COMPLETED	Combination Chemotherapy and Pegfilgrastim in Treating Patients With Previously Untreated Germ Cell Tumors
NCT02300987	PHASE2	COMPLETED	A Randomized, Blinded, Placebo-controlled, Phase II Trial of LEE011 in Patients With Relapsed, Refractory, Incurable Teratoma With Recent Progression
NCT00253539	PHASE2	COMPLETED	Arzoxifene or Tamoxifen in Preventing Breast Cancer in Premenopausal Women at High Risk for Breast Cancer
NCT00305695	PHASE2	COMPLETED	Zoledronate or Observation in Maintaining Bone Mineral Density in Patients Who Are Undergoing Surgery to Remove Both Ovaries
NCT00321633	PHASE2	COMPLETED	Carboplatin or Docetaxel in Treating Women With Metastatic Genetic Breast Cancer
NCT01333748	PHASE2	COMPLETED	Search Allelic Imbalance of Expression of BRCA Genes in Hereditary Risk of Breast and/or Ovarian Cancer
NCT01367639	PHASE2	COMPLETED	Trial of Inquiry Based Stress Reduction (IBSR) Program for BRCA1/2 Mutation Carriers
NCT00535119	PHASE1	COMPLETED	Veliparib, Carboplatin, and Paclitaxel in Treating Patients With Advanced Solid Cancer
NCT00892736	PHASE1	COMPLETED	Veliparib in Treating Patients With Malignant Solid Tumors That Do Not Respond to Previous Therapy
NCT00003643	PHASE2/PHASE3	UNKNOWN	Combination Chemotherapy in Treating Men With Germ Cell Cancer
NCT00423852	PHASE1/PHASE2	COMPLETED	Paclitaxel, Ifosfamide, and Carboplatin Followed By Autologous Stem Cell Transplant in Treating Patients With Germ Cell Tumors That Did Not Respond to Cisplatin
NCT00687778	Not specified	UNKNOWN	11C-Acetate PET/CT Non-FDG-Avid Tumors
NCT00836121	Not specified	COMPLETED	Anterior Mediastinum Teratoma: A Case Report
NCT05179850	Not specified	UNKNOWN	Computer Aided Diagnostic Tool on Computed Tomography Images for Diagnosis of Retroperitoneal Tumor in Children
NCT05187923	Not specified	UNKNOWN	Computer Aided Tool for Diagnosis of Neck Masses in Children
NCT05564026	Not specified	RECRUITING	Molecular Epidemiology of Pediatric Germ Cell Tumors
NCT06421805	Not specified	RECRUITING	Establishing Prospective Mediastinal Tumor Database of PUMCH
NCT07199699	Not specified	NOT_YET_RECRUITING	Subxiphoid VATS for Giant Mediastinal Teratoma
NCT03832985	EARLY_PHASE1	COMPLETED	Pediatric Reporting of Adult-Onset Genomic Results
NCT00005095	Not specified	RECRUITING	Specimen and Data Study for Ovarian Cancer Early Detection and Prevention
NCT00609505	Not specified	COMPLETED	Telemedicine vs. Face-to-Face Cancer Genetic Counseling
NCT01273909	Not specified	UNKNOWN	Outcomes After Perforator Flap Reconstruction for Breast Reconstruction and/or Lymphedema Treatment
NCT01445275	Not specified	WITHDRAWN	Cost of Cancer Risk Management in Women at Elevated Genetic Risk for Ovarian Cancer Who Participated on GOG-0199
NCT01608074	Not specified	ACTIVE_NOT_RECRUITING	Radical Fimbriectomy for Young BRCA Mutation Carriers
NCT02087592	Not specified	COMPLETED	Feasibility of Lifestyle Intervention in BRCA1/2 Mutation Carriers
NCT02302742	Not specified	RECRUITING	Triple Negative Breast Cancer and Germline Hereditary Breast and Ovarian Cancer Mutation Carrier Registry
NCT02324062	Not specified	COMPLETED	Cancer Genetics Hereditary Cancer Panel Testing
NCT02516540	Not specified	UNKNOWN	Efficacy of Lifestyle Intervention in BRCA1/2 Mutation Carriers
NCT02653105	Not specified	ACTIVE_NOT_RECRUITING	Women at Risk of Breast Cancer and OLFM4