APC

Summary

APC (APC regulator of Wnt signaling pathway, HGNC:583) is a protein-coding gene on chromosome 5q22.2, encoding Adenomatous polyposis coli protein (P25054). Tumor suppressor. In precision oncology, APC Mutation confers sensitivity to JW55 in Colon Carcinoma (CIViC Level D); 1 further curated variant–drug associations are listed below. It is a selective cancer dependency (DepMap: 26.6% of cell lines) and haploinsufficient (ClinGen: sufficient evidence).

This gene encodes a tumor suppressor protein that acts as an antagonist of the Wnt signaling pathway. It is also involved in other processes including cell migration and adhesion, transcriptional activation, and apoptosis. Defects in this gene cause familial adenomatous polyposis (FAP), an autosomal dominant pre-malignant disease that usually progresses to malignancy. Mutations in the APC gene have been found to occur in most colorectal cancers, where disease-associated mutations tend to be clustered in a small region designated the mutation cluster region (MCR) and result in a truncated protein product.

Source: NCBI Gene 324 — RefSeq curated summary.

At a glance

• Gene–disease (curated): gastric adenocarcinoma and proximal polyposis of the stomach (Definitive, ClinGen) — +7 more curated relationships
• GWAS associations: 12
• Clinical variants (ClinVar): 16,989 total — 2186 pathogenic, 280 likely-pathogenic
• Phenotypes (HPO): 139
• Druggable target: yes
• Precision-oncology evidence (CIViC): 2 curated variant–drug associations
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 22 cancer types
• Cancer dependency (DepMap): dependent in 26.6% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• Transcription factor: yes — 12 downstream targets (CollecTRI)
• MANE Select transcript: NM_000038

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:583
Approved symbol	APC
Name	APC regulator of Wnt signaling pathway
Location	5q22.2
Locus type	gene with protein product
Status	Approved
Aliases	DP2, DP3, DP2.5, PPP1R46
Ensembl gene	ENSG00000134982
Ensembl biotype	protein_coding
OMIM	611731
Entrez	324

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 11 protein_coding, 5 nonsense_mediated_decay, 1 retained_intron

ENST00000257430, ENST00000502371, ENST00000504915, ENST00000505084, ENST00000505350, ENST00000507379, ENST00000508376, ENST00000508624, ENST00000509732, ENST00000512211, ENST00000713636, ENST00000713637, ENST00000713638, ENST00000713639, ENST00000917934, ENST00000917935, ENST00000951167

RefSeq mRNA: 35 — MANE Select: NM_000038 NM_000038, NM_001127510, NM_001127511, NM_001354895, NM_001354896, NM_001354897, NM_001354898, NM_001354899, NM_001354900, NM_001354901, NM_001354902, NM_001354903, NM_001354904, NM_001354905, NM_001354906, NM_001407446, NM_001407447, NM_001407448, NM_001407449, NM_001407450, NM_001407451, NM_001407452, NM_001407453, NM_001407454, NM_001407455, NM_001407456, NM_001407457, NM_001407458, NM_001407459, NM_001407460, NM_001407467, NM_001407469, NM_001407470, NM_001407471, NM_001407472

CCDS: CCDS4107

Canonical transcript exons

ENST00000257430 — 16 exons

Exon	Start	End
ENSE00000917796	112766326	112766410
ENSE00002053882	112737885	112737925
ENSE00002085027	112767189	112767390
ENSE00003506518	112754873	112755025
ENSE00004011318	112827929	112828006
ENSE00004011319	112821896	112821991
ENSE00004011321	112815495	112815593
ENSE00004011325	112775629	112775737
ENSE00004011326	112801279	112801383
ENSE00004011331	112828856	112828972
ENSE00004011332	112818966	112819344
ENSE00004011333	112834951	112835165
ENSE00004011334	112827108	112827247
ENSE00004011335	112780790	112780903
ENSE00004011337	112792446	112792529
ENSE00004020542	112837553	112846239

Expression profiles

Bgee: expression breadth ubiquitous, 297 present calls, max score 97.87.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 21.1355 / max 2655.4186, expressed in 1757 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
57998	12.3441	1420
57995	7.8619	1612
58000	0.7609	92
58001	0.1319	59
57994	0.0366	14

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
substantia nigra pars compacta	UBERON:0001965	97.87	gold quality
substantia nigra pars reticulata	UBERON:0001966	97.08	gold quality
medial globus pallidus	UBERON:0002477	96.80	gold quality
cortical plate	UBERON:0005343	96.58	gold quality
lateral nuclear group of thalamus	UBERON:0002736	96.50	gold quality
Brodmann (1909) area 46	UBERON:0006483	96.43	gold quality
orbitofrontal cortex	UBERON:0004167	96.40	gold quality
CA1 field of hippocampus	UBERON:0003881	96.37	gold quality
ventricular zone	UBERON:0003053	96.32	gold quality
postcentral gyrus	UBERON:0002581	96.25	gold quality
globus pallidus	UBERON:0001875	96.08	gold quality
frontal pole	UBERON:0002795	96.05	gold quality
corpus callosum	UBERON:0002336	96.04	gold quality
parietal lobe	UBERON:0001872	95.96	gold quality
pons	UBERON:0000988	95.51	gold quality
superior frontal gyrus	UBERON:0002661	95.43	gold quality
pigmented layer of retina	UBERON:0001782	94.77	gold quality
retina	UBERON:0000966	94.74	gold quality
superior vestibular nucleus	UBERON:0007227	94.57	gold quality
lateral globus pallidus	UBERON:0002476	94.40	gold quality
entorhinal cortex	UBERON:0002728	94.27	gold quality
dorsal plus ventral thalamus	UBERON:0001897	94.26	gold quality
ganglionic eminence	UBERON:0004023	94.20	gold quality
Brodmann (1909) area 23	UBERON:0013554	94.06	gold quality
cranial nerve II	UBERON:0000941	93.97	gold quality
occipital lobe	UBERON:0002021	93.81	gold quality
Ammon’s horn	UBERON:0001954	93.75	gold quality
temporal lobe	UBERON:0001871	93.74	gold quality
amygdala	UBERON:0001876	93.73	gold quality
subthalamic nucleus	UBERON:0001906	93.67	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	70.65
E-GEOD-137537	yes	13.89
E-GEOD-84465	yes	11.41
E-ANND-3	yes	5.88

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

12 targets.

Target	Regulation
AKT1	Repression
AMHR2	Repression
BIRC5	Unknown
DLG1	Unknown
DNMT1	Repression
F8	Unknown
KLF4	Unknown
MYC	Repression
NOS2	Activation
ODC1	Repression
PTGS2	Repression
SGK1	Repression

Upstream regulators (CollecTRI, top): AP1, CDX1, CDX2, CEBPZ, CTNNBL1, DNMT1, DNMT3B, EGR1, EMX1, EZH2, GATA4, GATA5, GATA6, HIF1A, HNF4A, IRF6, JUN, KAT7, KMT2A, MYC, NFE2L2, PRDM5, RCOR2, SMAD7, SP3, TCF4, TP53, USF1, USF2, YY1

miRNA regulators (miRDB)

184 targeting APC, 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-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-302E	99.96	70.74	2669
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-3682-5P	99.93	67.97	1163
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-4778-3P	99.93	70.40	1818

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 26.6% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• Asp1822Val variant is a common polymorphism without clinical implications (PMID:11584047)
• Mutation analysis in northwest Spanish patients with familial adenomatous polyposis (FAP) and sporadic colorectal cancer (PMID:11668620)
• Results suggest that mutations of the beta-catenin and APC genes are rare and that activation of the Wnt signaling pathway may not contribute to pathogenesis in human papillary and follicular thyroid carcinomas. (PMID:11696170)
• Mutations in APC coding region are not the sole cause of FAP or CHRP (PMID:11741105)
• Nine mutations were novel and eight families were shown to harbor two recurrent mutations. (PMID:11748858)
• APC regulates survivin expression: a possible mechanism contributing to the stem cell origin of colon cancer. (PMID:11751382)
• Maternal mosaicism for a second mutational event-a novel deletion-in a familial adenomatous polyposis family harboring a new germ-line mutation in the alternatively spliced-exon 9 region of APC. (PMID:11754114)
• novel 3’ mutation in the APC gene in a family presenting with a desmoid tumour and minimal colonic phenotype (PMID:11768389)
• silent mutation in exon 14 of the APC gene is associated with exon skipping in a FAP family (PMID:11768390)
• Different combinations of biallelic APC mutation confer different growth advantages in colorectal tumours. (PMID:11809680)
• Quantitative adenomatous polyposis coli promoter methylation analysis in tumor tissue, serum, and plasma DNA of patients with lung cancer. (PMID:11809682)
• androgen receptor does not interact with adenomatous polyposis coli or glycogen synthase kinase-3beta and, therefore, conclude that androgen-mediated transport of beta-catenin occurs through a distinct pathway. (PMID:11856748)
• Older age and APC mutation in the central part of the gene are risk factors for the development of severe duodenojejunal polyposis. Location of the mutation affects severity of familial adenomatous polyposis. (PMID:11868006)
• Molecular alterations in the APC/beta-catenin pathway were detected in 23.5% (4 of 17) of the pancreatic acinar cell carcinomas (PMID:11891193)
• APC interacts with the kinesin superfamily (PMID:11912492)
• mutations rare in ulcerative colitis-related colorectal carcinomas; significant difference in frequency of APC mutations seen between right- and left-sided sporadic tumors suggests different molecular pathways (PMID:11920497)
• Three APC mutations have been identified in 22 tested samples, all of them in xenografts developed from metastatic prostate tumors. (PMID:11921277)
• APC germline mutations identified in Czech patients with familial adenomatous polyposis: includes 11 which were not previously reported (PMID:11933206)
• Dysfunction of APC may be a major cause of changes in beta-catenin function in colorectal tumors. (PMID:11956815)
• Association and regulation of casein kinase 2 activity by adenomatous polyposis coli protein (PMID:11972058)
• alleles produce functional protein from internal translation initiation (PMID:12034871)
• results indicate selection for APC genotypes that are likely to retain some activity in downregulating beta-catenin signaling (PMID:12045208)
• demonstration of the direct interaction of APC-(129-250) fragment with the nuclear export factor chromosome maintenance region 1 (Crm-1) (PMID:12070164)
• Mutations in APC, Kirsten-ras, and p53–alternative genetic pathways to colorectal cancer. The most common combination of mutations was p53 and APC (27.1%), whereas mutations in both p53 and K-ras were extremely rare. (PMID:12093899)
• Molecular genetic analysis of malignant melanomas for aberrations of the WNT signaling pathway genes CTNNB1, APC, ICAT and BTRC. (PMID:12124804)
• Different familial adenomatous polyposis phenotypes resulting from deletions of the entire APC exon 15 (PMID:12136240)
• somatic mutation of the APC gene plays an important role in the pathogenesis of gastric adenoma and dysplasia (PMID:12163385)
• Pathogenic mutations and rare variants of the gene identified in 75 Belgian patients with familial adenomatous polyposis by fluorescent enzymatic mutation detection (PMID:12173026)
• Alternations in the APC gene mutations are involved in tumor growth and in tumor progression. (PMID:12374230)
• APC mutation is involved in carcinogenesis of intestinal type of gastric cancer and is independent of MSI phenotype but related to the LOH pathway in gastric cancer. (PMID:12378616)
• role in mediating growth-suppressive effect of gut-enriched Kruppel-like factor (PMID:12387883)
• implication of activation of the APC/beta-catenin signalling pathway due to beta-catenin mutations in the development of a subset of endometrial carcinomas (PMID:12439748)
• structure of the amino-terminal nuclear export domain (PMID:12485844)
• Partial loss of function of APC protein by truncation of its carboxy(C)-terminus is an early factor in the development of many colorectal neoplasms. (PMID:12504226)
• Human DNA methyltransferase gene DNMT1 is regulated by the APC pathway (PMID:12538344)
• In human pilomatricoma,loss of heterozygosity was observed in the APC gene, but no mutations in the mutation cluster region were found in seven tumours without beta-catenin mutations. (PMID:12575848)
• Novel mutations of the APC gene in familial adenomatous polyposis in Greek patients. (PMID:12581900)
• Data indicate that the rate of nuclear export of adenomatous polyposis coli protein (APC), rather than its nuclear import or steady-state levels, determines the transcriptional activity of beta-catenin. (PMID:12606575)
• study verified reduced expressions of adenomatous polyposis coli and E-cadherin proteins in colorectal cancer cells and suggests that normal protein expressions in benign epithelium are progressively and independently lost in sporadic colorectal cancers (PMID:12647217)
• The APC I1307K mutation may contribute to colorectal cancers (CRC) in Israeli Arabs; inactivating mutations of MSH2 and MLH1 may not be a major cause for early onset CRC. (PMID:12655564)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	apc	ENSDARG00000058868
mus_musculus	Apc	ENSMUSG00000005871
rattus_norvegicus	Apc	ENSRNOG00000020423
drosophila_melanogaster	Apc	FBGN0015589
drosophila_melanogaster	Apc2	FBGN0026598
caenorhabditis_elegans	apr-1	WBGENE00000156

Paralogs (1): APC2 (ENSG00000115266)

Protein

Protein identifiers

Adenomatous polyposis coli protein — P25054 (reviewed: P25054)

Alternative names: Deleted in polyposis 2.5

All UniProt accessions (12): A0A087WYF3, A0A087X2F3, A0A2Q2SV78, A0AAQ5BGI9, A0AAQ5BGJ9, A0AAQ5BGK6, A0AAQ5BGM3, D6RFL6, E7EMH9, E9PFT7, P25054, R4GMU6

UniProt curated annotations — full annotation on UniProt →

Function. Tumor suppressor. Promotes rapid degradation of CTNNB1 and participates in Wnt signaling as a negative regulator. APC activity is correlated with its phosphorylation state. Activates the GEF activity of SPATA13 and ARHGEF4. Plays a role in hepatocyte growth factor (HGF)-induced cell migration. Required for MMP9 up-regulation via the JNK signaling pathway in colorectal tumor cells. Associates with both microtubules and actin filaments, components of the cytoskeleton. Plays a role in mediating the organization of F-actin into ordered bundles. Functions downstream of Rho GTPases and DIAPH1 to selectively stabilize microtubules. Acts as a mediator of ERBB2-dependent stabilization of microtubules at the cell cortex. It is required for the localization of MACF1 to the cell membrane and this localization of MACF1 is critical for its function in microtubule stabilization.

Subunit / interactions. Forms homooligomers. Found in a complex consisting of ARHGEF4, APC and CTNNB1. Found in a complex composed of MACF1, APC, AXIN1, CTNNB1 and GSK3B. The complex composed, at least, of APC, CTNNB1 and GSK3B interacts with JPT1; the interaction requires the inactive form of GSK3B (phosphorylated at ‘Ser-9’). Interacts with APC2. Interacts with DLG1 (via PDZ domains) and DLG3 (via PDZ domains). Interacts with alpha- and beta-catenins. Interacts with AXIN1 (via RGS domain). Interacts with ARHGEF4 (via N-terminus). Interacts (via C-terminal residues 2674-2843) with MAPRE1 (via C-terminal residues 206-211); the interaction inhibits association with and bundling of F-actin. Interacts with MAPRE2 and MAPRE3 (via C-terminus). Interacts with DIAPH1; DIAPH1 acts as a scaffold protein for MAPRE1 and APC to stabilize microtubules and promote cell migration. Interacts with DIAPH2. Interacts with SCRIB; may mediate APC targeting to adherens junctions of epithelial cells. Interacts with SPATA13 (via N-terminus and SH3 domain). Interacts with ASAP1 (via SH3 domain). Interacts (at the cell membrane) with AMER1 and AMER2 (via ARM repeats). Interacts with KHDRBS1. Interacts with actin; binds both to F-actin and actin filament bundles.

Subcellular location. Cell junction. Adherens junction. Cytoplasm. Cytoskeleton. Cell projection. Lamellipodium. Ruffle membrane. Cell membrane.

Tissue specificity. Expressed in a variety of tissues: brain, small intestine, colon, thymus, skeletal muscle, heart, prostate, lung, spleen, ovary, testis kidney, placenta, blood and liver. Isoform 1A: Very strongly expressed in brain but has relatively low expression levels in other tissues. Isoform 1B: Predominant form in all tissues except for brain, including gastric mucosa and blood.

Post-translational modifications. Phosphorylated; phosphorylation enhances the F-actin bundling activity. Phosphorylated by GSK3B. Ubiquitinated, leading to its degradation by the proteasome. Ubiquitination is facilitated by Axin. Deubiquitinated by ZRANB1/TRABID.

Disease relevance. Familial adenomatous polyposis 1 (FAP1) [MIM:175100] An autosomal dominant cancer predisposition syndrome characterized by adenomatous polyps of the colon and rectum, but also of upper gastrointestinal tract (ampullary, duodenal and gastric adenomas). This is a viciously premalignant disease with one or more polyps progressing through dysplasia to malignancy in untreated gene carriers with a median age at diagnosis of 40 years. The disease is caused by variants affecting the gene represented in this entry. Desmoid disease, hereditary (DESMD) [MIM:135290] An autosomal dominant disease characterized by multifocal fibromatosis of the abdominal wall and mesentery. Desmoid tumors can also affect paraspinal muscles, breast, occiput, arms, and lower ribs. The disease is caused by variants affecting the gene represented in this entry. Medulloblastoma (MDB) [MIM:155255] Malignant, invasive embryonal tumor of the cerebellum with a preferential manifestation in children. The gene represented in this entry may be involved in disease pathogenesis. Gastric cancer (GASC) [MIM:613659] A malignant disease which starts in the stomach, can spread to the esophagus or the small intestine, and can extend through the stomach wall to nearby lymph nodes and organs. It also can metastasize to other parts of the body. The term gastric cancer or gastric carcinoma refers to adenocarcinoma of the stomach that accounts for most of all gastric malignant tumors. Two main histologic types are recognized, diffuse type and intestinal type carcinomas. Diffuse tumors are poorly differentiated infiltrating lesions, resulting in thickening of the stomach. In contrast, intestinal tumors are usually exophytic, often ulcerating, and associated with intestinal metaplasia of the stomach, most often observed in sporadic disease. The gene represented in this entry may be involved in disease pathogenesis. Hepatocellular carcinoma (HCC) [MIM:114550] A primary malignant neoplasm of epithelial liver cells. The major risk factors for HCC are chronic hepatitis B virus (HBV) infection, chronic hepatitis C virus (HCV) infection, prolonged dietary aflatoxin exposure, alcoholic cirrhosis, and cirrhosis due to other causes. The gene represented in this entry may be involved in disease pathogenesis. Gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS) [MIM:619182] A familial gastric polyposis syndrome characterized by autosomal dominant transmission of fundic gland polyposis with occasional hyperplastic and adenomatous polyps, sparing of the gastric antrum, and a significant risk of intestinal-type gastric adenocarcinoma development. Colorectal polyposis is not observed, and family history does not include colorectal cancer. The gene represented in this entry may be involved in disease pathogenesis.

Domain organisation. The microtubule tip localization signal (MtLS) motif; mediates interaction with MAPRE1 and targeting to the growing microtubule plus ends. The basic region (residues 2167-2674) mediates the association with both microtubule and actin proteins and promotes the bundling of F-actin.

Miscellaneous. APC mutations have led to some interesting observations. (1) the great majority of the mutations found to date would result in truncation of the APC product. (2) almost all the mutations have occurred within the first half of the coding sequence, and somatic mutations in colorectal tumors are further clustered in a particular region, called MCR (mutation cluster region). (3) most identified point mutations in the APC gene are transitions from cytosine to other nucleotides. (4) the location of germline mutations tends to correlate with the number of colorectal polyps in FAP1 patients. Inactivation of both alleles of the APC gene seems to be required as an early event to develop most adenomas and carcinomas in the colon and rectum as well as some of those in the stomach. Produced by alternative promoter usage.

Similarity. Belongs to the adenomatous polyposis coli (APC) family.

Isoforms (3)

UniProt ID	Names	Canonical?
P25054-1	1A, Long	yes
P25054-2	2, Short
P25054-3	1B

RefSeq proteins (35): NP_000029, NP_001120982, NP_001120983, NP_001341824, NP_001341825, NP_001341826, NP_001341827, NP_001341828, NP_001341829, NP_001341830, NP_001341831, NP_001341832, NP_001341833, NP_001341834, NP_001341835, NP_001394375, NP_001394376, NP_001394377, NP_001394378, NP_001394379, NP_001394380, NP_001394381, NP_001394382, NP_001394383, NP_001394384, NP_001394385, NP_001394386, NP_001394387, NP_001394388, NP_001394389, NP_001394396, NP_001394398, NP_001394399, NP_001394400, NP_001394401 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000225	Armadillo	Repeat
IPR009223	APC_rpt	Repeat
IPR009224	SAMP	Repeat
IPR009232	EB1-bd	Domain
IPR009234	APC_basic_dom	Domain
IPR009240	APC_15aa_rpt	Repeat
IPR011989	ARM-like	Homologous_superfamily
IPR016024	ARM-type_fold	Homologous_superfamily
IPR026818	Apc_fam	Family
IPR026831	APC_dom	Homologous_superfamily
IPR032038	APC_N	Domain
IPR036149	APC_N_sf	Homologous_superfamily
IPR041257	APC_rep	Repeat

Pfam: PF00514, PF05923, PF05924, PF05937, PF05956, PF05972, PF11414, PF16629, PF16630, PF16633, PF16634, PF16635, PF16636, PF16689, PF18797

UniProt features (227 total): sequence variant 46, compositionally biased region 43, modified residue 42, helix 36, region of interest 25, sequence conflict 8, repeat 7, mutagenesis site 4, strand 4, splice variant 3, turn 3, coiled-coil region 2, short sequence motif 2, initiator methionine 1, chain 1

Structure

Experimental structures (PDB)

31 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
5IZA	X-RAY DIFFRACTION	1.5
3NMW	X-RAY DIFFRACTION	1.6
4YK6	X-RAY DIFFRACTION	1.7
5Z8H	X-RAY DIFFRACTION	1.79
1EMU	X-RAY DIFFRACTION	1.9
4YJE	X-RAY DIFFRACTION	1.9
5B6G	X-RAY DIFFRACTION	1.99
1M5I	X-RAY DIFFRACTION	2
4G69	X-RAY DIFFRACTION	2
8X2Q	X-RAY DIFFRACTION	2
1T08	X-RAY DIFFRACTION	2.1
1V18	X-RAY DIFFRACTION	2.1
3AU3	X-RAY DIFFRACTION	2.1
4YJL	X-RAY DIFFRACTION	2.1
7XTY	X-RAY DIFFRACTION	2.1
8GSJ	X-RAY DIFFRACTION	2.1
5IZ6	X-RAY DIFFRACTION	2.15
3RL8	X-RAY DIFFRACTION	2.2
3NMX	X-RAY DIFFRACTION	2.3
3RL7	X-RAY DIFFRACTION	2.3
1DEB	X-RAY DIFFRACTION	2.4
3QHE	X-RAY DIFFRACTION	2.4
7F6M	X-RAY DIFFRACTION	2.4
1TH1	X-RAY DIFFRACTION	2.5
7F7O	X-RAY DIFFRACTION	2.8
3T7U	X-RAY DIFFRACTION	2.9
5IZ9	X-RAY DIFFRACTION	2.93
3NMZ	X-RAY DIFFRACTION	3.01
5IZ8	X-RAY DIFFRACTION	3.06
1JPP	X-RAY DIFFRACTION	3.1

Predicted structure (AlphaFold)

No AlphaFold model available for P25054 — AlphaFold DB does not currently provide models for proteins above ~3000 aa.

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 (42): 1863, 1864, 1971, 1973, 2088, 2093, 2125, 2129, 2130, 2132, 2151, 2260, 2270, 2283, 2473, 2535, 2569, 2671, 2674, 2679 …

Mutagenesis-validated functional residues (4):

Position	Phenotype
516	impairs interaction with khdrbs1.
549	impairs interaction with khdrbs1.
2841	loss of interaction with scrib.
2843	loss of interaction with scrib.

Function

Pathways and Gene Ontology

Reactome pathways

31 pathways

ID	Pathway
R-HSA-111465	Apoptotic cleavage of cellular proteins
R-HSA-195253	Degradation of beta-catenin by the destruction complex
R-HSA-196299	Beta-catenin phosphorylation cascade
R-HSA-3769402	Deactivation of the beta-catenin transactivating complex
R-HSA-4641262	Disassembly of the destruction complex and recruitment of AXIN to the membrane
R-HSA-5339716	Signaling by GSK3beta mutants
R-HSA-5358747	CTNNB1 S33 mutants aren’t phosphorylated
R-HSA-5358749	CTNNB1 S37 mutants aren’t phosphorylated
R-HSA-5358751	CTNNB1 S45 mutants aren’t phosphorylated
R-HSA-5358752	CTNNB1 T41 mutants aren’t phosphorylated
R-HSA-5467333	APC truncation mutants are not K63 polyubiquitinated
R-HSA-5467337	APC truncation mutants have impaired AXIN binding
R-HSA-5467340	AXIN missense mutants destabilize the destruction complex
R-HSA-5467348	Truncations of AMER1 destabilize the destruction complex
R-HSA-5689896	Ovarian tumor domain proteases
R-HSA-109581	Apoptosis
R-HSA-162582	Signal Transduction
R-HSA-1643685	Disease
R-HSA-195721	Signaling by WNT
R-HSA-201681	TCF dependent signaling in response to WNT
R-HSA-392499	Metabolism of proteins
R-HSA-4791275	Signaling by WNT in cancer
R-HSA-4839735	Signaling by AXIN mutants
R-HSA-4839743	Signaling by CTNNB1 phospho-site mutants
R-HSA-4839744	Signaling by APC mutants
R-HSA-4839748	Signaling by AMER1 mutants
R-HSA-5357801	Programmed Cell Death
R-HSA-5663202	Diseases of signal transduction by growth factor receptors and second messengers
R-HSA-5688426	Deubiquitination
R-HSA-597592	Post-translational protein modification

MSigDB gene sets: 862 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_UP, GOBP_MITOTIC_CYTOKINESIS, GOBP_CHROMOSOME_ORGANIZATION, GOBP_ATTACHMENT_OF_SPINDLE_MICROTUBULES_TO_KINETOCHORE, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_PROTEIN_LOCALIZATION_TO_CYTOSKELETON, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_NEGATIVE_REGULATION_OF_KINASE_ACTIVITY, GOBP_REGULATION_OF_NUCLEAR_DIVISION, GOBP_ENDOCARDIAL_CUSHION_DEVELOPMENT, LI_PROSTATE_CANCER_EPIGENETIC, GOBP_CHROMOSOME_LOCALIZATION

GO Biological Process (32): mitotic cytokinesis (GO:0000281), cell fate specification (GO:0001708), heart valve development (GO:0003170), endocardial cushion morphogenesis (GO:0003203), DNA damage response (GO:0006974), negative regulation of microtubule depolymerization (GO:0007026), mitotic spindle assembly checkpoint signaling (GO:0007094), cell adhesion (GO:0007155), pattern specification process (GO:0007389), nervous system development (GO:0007399), negative regulation of cell population proliferation (GO:0008285), insulin receptor signaling pathway (GO:0008286), Wnt signaling pathway (GO:0016055), cell migration (GO:0016477), positive regulation of cell migration (GO:0030335), positive regulation of pseudopodium assembly (GO:0031274), regulation of microtubule-based process (GO:0032886), positive regulation of apoptotic process (GO:0043065), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161), positive regulation of protein catabolic process (GO:0045732), negative regulation of cyclin-dependent protein serine/threonine kinase activity (GO:0045736), regulation of attachment of spindle microtubules to kinetochore (GO:0051988), regulation of microtubule-based movement (GO:0060632), protein-containing complex assembly (GO:0065003), bicellular tight junction assembly (GO:0070830), negative regulation of canonical Wnt signaling pathway (GO:0090090), positive regulation of cold-induced thermogenesis (GO:0120162), negative regulation of cell cycle G1/S phase transition (GO:1902807), positive regulation of protein localization to centrosome (GO:1904781), negative regulation of G1/S transition of mitotic cell cycle (GO:2000134), negative regulation of Wnt signaling pathway (GO:0030178), regulation of primary metabolic process (GO:0080090)

GO Molecular Function (10): beta-catenin binding (GO:0008013), microtubule binding (GO:0008017), protein kinase regulator activity (GO:0019887), protein kinase binding (GO:0019901), ubiquitin protein ligase binding (GO:0031625), gamma-catenin binding (GO:0045295), microtubule plus-end binding (GO:0051010), dynein complex binding (GO:0070840), protein binding (GO:0005515), protein-containing complex binding (GO:0044877)

GO Cellular Component (28): kinetochore (GO:0000776), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), Golgi apparatus (GO:0005794), centrosome (GO:0005813), cytosol (GO:0005829), microtubule (GO:0005874), plasma membrane (GO:0005886), adherens junction (GO:0005912), bicellular tight junction (GO:0005923), lateral plasma membrane (GO:0016328), catenin complex (GO:0016342), lamellipodium (GO:0030027), beta-catenin destruction complex (GO:0030877), ruffle membrane (GO:0032587), perinuclear region of cytoplasm (GO:0048471), Wnt signalosome (GO:1990909), cytoskeleton (GO:0005856), cytoplasmic microtubule (GO:0005881), microtubule cytoskeleton (GO:0015630), membrane (GO:0016020), cell junction (GO:0030054), leading edge membrane (GO:0031256), cell projection (GO:0042995), anchoring junction (GO:0070161), cell periphery (GO:0071944), plasma membrane bounded cell projection (GO:0120025)

Reactome top-level categories

Rollup of top-12 pathways:

Category	Pathways
Signaling by CTNNB1 phospho-site mutants	4
Signaling by WNT	2
TCF dependent signaling in response to WNT	2
Signaling by APC mutants	2
Apoptotic execution phase	1
Degradation of beta-catenin by the destruction complex	1
Signaling by WNT in cancer	1
Signaling by AXIN mutants	1
Signaling by AMER1 mutants	1
Deubiquitination	1
Programmed Cell Death	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
cytoplasm	4
mitotic cell cycle	2
protein binding	2
binding	2
intracellular membraneless organelle	2
intracellular membrane-bounded organelle	2
cytoskeleton-dependent cytokinesis	1
mitotic cell cycle process	1
cell fate commitment	1
cellular developmental process	1
heart development	1
anatomical structure development	1
heart morphogenesis	1
endocardial cushion development	1
mesenchyme morphogenesis	1
cellular response to stress	1
microtubule depolymerization	1
negative regulation of microtubule polymerization or depolymerization	1
regulation of microtubule depolymerization	1
negative regulation of protein depolymerization	1
negative regulation of supramolecular fiber organization	1
negative regulation of mitotic metaphase/anaphase transition	1
spindle assembly checkpoint signaling	1
mitotic spindle checkpoint signaling	1
cellular process	1
multicellular organism development	1
multicellular organismal process	1
system development	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
cell surface receptor protein tyrosine kinase signaling pathway	1
cellular response to insulin stimulus	1
cell surface receptor signaling pathway	1
cell motility	1
cell migration	1
regulation of cell migration	1
positive regulation of cell motility	1
pseudopodium assembly	1

Protein interactions and networks

STRING

1835 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
APC	GSK3B	P49841	997
APC	AXIN1	O15169	996
APC	CTNNB1	P35222	996
APC	CSNK1A1	P48729	994
APC	AXIN2	Q9Y2T1	994
APC	GSK3A	P49840	968
APC	BTRC	Q9Y297	963
APC	TFDP3	Q5H9I0	881
APC	ARHGEF4	Q9NR80	868
APC	DVL1	O14640	808
APC	HRK	O00198	786
APC	HNF4A	P41235	785
APC	CLIP1	P30622	750
APC	AMER1	Q5JTC6	732
APC	IQGAP1	P46940	731

IntAct

520 interactions, top by confidence:

A	B	Type	Score
APC	CTNNB1	psi-mi:“MI:0915”(physical association)	0.960
CTNNB1	APC	psi-mi:“MI:0407”(direct interaction)	0.960
CTNNB1	APC	psi-mi:“MI:0915”(physical association)	0.960
CTNNB1	AXIN1	psi-mi:“MI:0914”(association)	0.940
AXIN1	APC	psi-mi:“MI:0407”(direct interaction)	0.850
DLG1	APC	psi-mi:“MI:0407”(direct interaction)	0.840
APC	DLG1	psi-mi:“MI:0407”(direct interaction)	0.840
MAPRE1	APC	psi-mi:“MI:0915”(physical association)	0.830
MAPRE1	APC	psi-mi:“MI:0407”(direct interaction)	0.830
APC	MAPRE1	psi-mi:“MI:0407”(direct interaction)	0.830
CTBP1	ZEB2	psi-mi:“MI:0914”(association)	0.800
SCRIB	APC	psi-mi:“MI:0407”(direct interaction)	0.780
APC	CSNK1E	psi-mi:“MI:0217”(phosphorylation reaction)	0.740
AMER1	APC	psi-mi:“MI:0915”(physical association)	0.720
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CTBP1	CBX4	psi-mi:“MI:0914”(association)	0.700
SPATA13	APC	psi-mi:“MI:0915”(physical association)	0.670
APC	SPATA13	psi-mi:“MI:0915”(physical association)	0.670
SPATA13	APC	psi-mi:“MI:0403”(colocalization)	0.670

BioGRID (548): APC (Affinity Capture-Western), APC (Affinity Capture-Western), APC (Reconstituted Complex), APC (Affinity Capture-MS), APC (Affinity Capture-MS), APC (Affinity Capture-MS), APC (Affinity Capture-MS), APC (Affinity Capture-MS), APC (Affinity Capture-MS), AGR3 (Two-hybrid), CASC3 (Two-hybrid), CCL5 (Two-hybrid), CYP17A1 (Two-hybrid), DIRAS3 (Two-hybrid), DKK3 (Two-hybrid)

ESM2 similar proteins: A0A571BF63, A0JMA8, A1A535, A1A5P5, A1ZBE8, A6H8H2, A8XSV3, B0BF33, B2RS91, E7F187, O17237, O43150, P25054, P30630, Q05B30, Q09263, Q14156, Q14738, Q14D04, Q19317, Q1AAU6, Q21106, Q2KI89, Q5PQS3, Q5R4N9, Q5R629, Q5RAY1, Q5SPP5, Q5U245, Q5VZ89, Q61315, Q61QK6, Q620W3, Q641A2, Q6ZQ18, Q7SIG6, Q7Z3E5, Q7Z401, Q7Z7A4, Q8BG67

Diamond homologs: A8X633, O95996, P25054, P70478, Q21227, Q61315, Q9Z1K7, P70039

SIGNOR signaling

17 interactions.

A	Effect	B	Mechanism
CSNK1E	“up-regulates activity”	APC	phosphorylation
DVL1	“down-regulates activity”	APC	binding
APC	“down-regulates quantity”	CTNNB1	binding
CDC14B	up-regulates	APC	dephosphorylation
AMER1	up-regulates	APC	relocalization
APC	“form complex”	GSK3B/Axin/APC	binding
PRKACA	“down-regulates activity”	APC	phosphorylation
KRT1	“up-regulates activity”	APC	phosphorylation
APC	“down-regulates quantity by repression”	ODC1	“transcriptional regulation”
CHRNB3	“up-regulates activity”	APC	binding
APC	“form complex”	SCF(TBL1)	binding
BUB1B	“up-regulates activity”	APC	phosphorylation
PRKCD	“down-regulates activity”	APC	phosphorylation
AXIN1	“up-regulates activity”	APC	binding
GSK3B	up-regulates	APC	phosphorylation
AXIN2	up-regulates	APC	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 177 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
IPs transport between nucleus and cytosol	10	31.2×	1e-10
IP3 and IP4 transport between cytosol and nucleus	10	31.2×	1e-10
IP6 and IP7 transport between cytosol and nucleus	10	31.2×	1e-10
Activation of BAD and translocation to mitochondria	5	31.2×	8e-06
Transport of Ribonucleoproteins into the Host Nucleus	10	29.2×	1e-10
Regulation of Glucokinase by Glucokinase Regulatory Protein	10	29.2×	1e-10
Defective TPR may confer susceptibility towards thyroid papillary carcinoma (TPC)	10	29.2×	1e-10
SRC activates STAT3 in a quantitative manner, through Cadherin-11 (CDH11), RAC1 and gp130 (IL6ST)	7	28.5×	9e-08

GO biological processes:

GO term	Partners	Fold	FDR
RNA export from nucleus	6	35.8×	4e-06
regulation of stress fiber assembly	5	31.6×	8e-05
nucleocytoplasmic transport	10	25.0×	7e-09
microtubule bundle formation	6	19.5×	1e-04
mRNA transport	8	13.4×	4e-05
morphogenesis of an epithelium	6	13.1×	8e-04
establishment or maintenance of cell polarity	5	12.8×	4e-03
intermediate filament organization	8	12.3×	7e-05

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 22 cancer types — AML, ANSC, CHOL, COAD, COADREAD, CSCC, EGC, ESCA, ESCC, HCC, LUAD, MEL…(+10 more).

Clinical variants and AI predictions

ClinVar

16989 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	2186
Likely pathogenic	280
Uncertain significance	6100
Likely benign	1907
Benign	415

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1012191	NM_000038.6(APC):c.1490dup (p.Arg498fs)	Pathogenic
1012192	NM_000038.6(APC):c.1744G>T (p.Glu582Ter)	Pathogenic
1012193	NM_000038.6(APC):c.2510del (p.Ser836_Ser837insTer)	Pathogenic
1048837	NM_000038.6(APC):c.1742_1743del (p.Lys581fs)	Pathogenic
1048908	NM_000038.6(APC):c.3470dup (p.Arg1158fs)	Pathogenic
1049076	NM_000038.6(APC):c.-2_136-2903del	Pathogenic
1049077	NM_000038.6(APC):c.2893_2896del (p.Asn965fs)	Pathogenic
1049123	NM_000038.6(APC):c.5782del (p.Gln1928fs)	Pathogenic
1049151	NM_000038.6(APC):c.442del (p.Asp149fs)	Pathogenic
1049324	NM_000038.6(APC):c.-2_135+1274del	Pathogenic
1049327	NM_000038.6(APC):c.3411del (p.Asp1137fs)	Pathogenic
1049497	NM_000038.6(APC):c.1744-2_1958+1del	Pathogenic
1049574	NM_000038.6(APC):c.1259_1269del (p.Cys420fs)	Pathogenic
1049668	NM_000038.6(APC):c.4945dup (p.Ile1649fs)	Pathogenic
1049778	NM_000038.6(APC):c.-2_135+1824del	Pathogenic
1049811	NM_000038.6(APC):c.194del (p.Gln65fs)	Pathogenic
1049856	NM_000038.6(APC):c.4268_4271del (p.Leu1423fs)	Pathogenic
1049899	NM_000038.6(APC):c.423-3_531+198del	Pathogenic
1050064	NM_000038.6(APC):c.841dup (p.Thr281fs)	Pathogenic
1050121	NM_000038.6(APC):c.3260_3263dup (p.Lys1088fs)	Pathogenic
1050133	NM_000038.6(APC):c.1046_1140del (p.Gln349fs)	Pathogenic
1050316	NM_000038.6(APC):c.2928_2929del (p.Gly977fs)	Pathogenic
1050389	NM_000038.6(APC):c.2487del (p.Val830fs)	Pathogenic
1050412	NM_001127511.3(APC):c.166-28469_166-27547del	Pathogenic
1050449	NM_000038.6(APC):c.3847del (p.Ala1283fs)	Pathogenic
1050476	NM_000038.6(APC):c.3026del (p.His1009fs)	Pathogenic
1050551	NM_000038.6(APC):c.4606G>T (p.Glu1536Ter)	Pathogenic
1050584	NM_001127511.3(APC):c.166-28467del	Pathogenic
1050611	NM_000038.6(APC):c.1313-2_1743+144del	Pathogenic
1050614	NM_000038.6(APC):c.4164_4165del (p.Ser1389fs)	Pathogenic

SpliceAI

2738 predictions. Top by Δscore:

Variant	Effect	Δscore
5:112738138:G:GT	donor_gain	1.0000
5:112766323:CAGG:C	acceptor_loss	1.0000
5:112766324:A:AG	acceptor_gain	1.0000
5:112766324:A:T	acceptor_loss	1.0000
5:112766324:AG:A	acceptor_gain	1.0000
5:112766325:G:GG	acceptor_gain	1.0000
5:112766325:GG:G	acceptor_gain	1.0000
5:112766325:GGA:G	acceptor_gain	1.0000
5:112766325:GGAA:G	acceptor_gain	1.0000
5:112780781:T:TA	acceptor_gain	1.0000
5:112780788:A:AG	acceptor_gain	1.0000
5:112780789:G:GA	acceptor_gain	1.0000
5:112780789:GT:G	acceptor_gain	1.0000
5:112780789:GTT:G	acceptor_gain	1.0000
5:112780789:GTTT:G	acceptor_gain	1.0000
5:112780789:GTTTT:G	acceptor_gain	1.0000
5:112780900:ACAG:A	donor_gain	1.0000
5:112780901:CAG:C	donor_gain	1.0000
5:112780901:CAGGT:C	donor_loss	1.0000
5:112780902:AG:A	donor_gain	1.0000
5:112780903:GG:G	donor_gain	1.0000
5:112780904:G:GG	donor_gain	1.0000
5:112780905:T:A	donor_loss	1.0000
5:112792439:A:AG	acceptor_gain	1.0000
5:112792440:T:G	acceptor_gain	1.0000
5:112792441:TTTA:T	acceptor_loss	1.0000
5:112792442:TTAGC:T	acceptor_loss	1.0000
5:112792444:A:AG	acceptor_gain	1.0000
5:112792444:AGC:A	acceptor_gain	1.0000
5:112792445:G:GG	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000008168 (5:112708367 G>A,C), RS1000008920 (5:112718172 A>G,T), RS1000038075 (5:112797060 CTTGT>C), RS1000065592 (5:112755147 T>G), RS1000080377 (5:112745683 C>A,G), RS1000121955 (5:112833521 G>T), RS1000132371 (5:112746544 T>C), RS1000193346 (5:112786250 G>T), RS1000252916 (5:112760545 A>C), RS1000285252 (5:112806935 C>T), RS1000307225 (5:112812063 C>T), RS1000316446 (5:112796043 C>G), RS1000332017 (5:112770763 T>G), RS1000344219 (5:112744606 C>G), RS1000349693 (5:112802682 A>G,T)

Disease associations

OMIM: gene MIM:611731 | disease phenotypes: MIM:175100, MIM:613659, MIM:114500, MIM:114550, MIM:175505, MIM:619182, MIM:135290, MIM:114480, MIM:167000, MIM:606764

GenCC curated gene-disease

Disease	Classification	Inheritance
familial adenomatous polyposis 1	Definitive	Autosomal dominant
gastric adenocarcinoma and proximal polyposis of the stomach	Definitive	Autosomal dominant
classic or attenuated familial adenomatous polyposis	Definitive	Autosomal dominant
desmoid tumor	Definitive	Autosomal dominant
sarcoma	Moderate	Autosomal dominant
APC-related attenuated familial adenomatous polyposis	Supportive	Autosomal dominant
Cenani-Lenz syndactyly syndrome	Supportive	Autosomal recessive
Turcot syndrome with polyposis	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (2)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
gastric adenocarcinoma and proximal polyposis of the stomach	Definitive	AD
classic or attenuated familial adenomatous polyposis	Definitive	AD

Mondo (51): familial adenomatous polyposis 1 (MONDO:0021056), hereditary neoplastic syndrome (MONDO:0015356), classic or attenuated familial adenomatous polyposis (MONDO:0021057), gastric cancer (MONDO:0001056), colorectal cancer (MONDO:0005575), hepatocellular carcinoma (MONDO:0007256), gastric adenocarcinoma and proximal polyposis of the stomach (MONDO:0017790), colon carcinoma (MONDO:0002032), desmoid tumor (MONDO:0007608), breast cancer (MONDO:0007254), classic familial adenomatous polyposis (MONDO:0021055), hereditary breast carcinoma (MONDO:0016419), APC-related attenuated familial adenomatous polyposis (MONDO:0016613), colorectal adenoma (MONDO:0005484), familial colorectal cancer (MONDO:0023113)

Orphanet (20): Inherited cancer-predisposing syndrome (Orphanet:140162), Gastric adenocarcinoma and proximal polyposis of the stomach (Orphanet:314022), Desmoid tumor (Orphanet:873), Hepatocellular carcinoma (Orphanet:88673), Familial adenomatous polyposis (Orphanet:733), Hereditary breast cancer (Orphanet:227535), Rare ovarian cancer (Orphanet:213500), 5q22 microdeletion syndrome (Orphanet:261584), Hepatoblastoma (Orphanet:449), Attenuated familial adenomatous polyposis (Orphanet:220460), Hereditary breast and/or ovarian cancer syndrome (Orphanet:145), Gastrointestinal stromal tumor (Orphanet:44890), Cancer of unknown primary site (Orphanet:631251), Perihilar cholangiocarcinoma (Orphanet:99978), Craniopharyngioma (Orphanet:54595)

HPO phenotypes

139 total (30 of 139 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000077	Abnormality of the kidney
HP:0000126	Hydronephrosis
HP:0000131	Uterine leiomyoma
HP:0000160	Narrow mouth
HP:0000215	Thick upper lip vermilion
HP:0000218	High palate
HP:0000272	Malar flattening
HP:0000276	Long face
HP:0000303	Mandibular prognathia
HP:0000316	Hypertelorism
HP:0000322	Short philtrum
HP:0000343	Long philtrum
HP:0000347	Micrognathia
HP:0000348	High forehead
HP:0000365	Hearing impairment
HP:0000411	Protruding ear
HP:0000444	Convex nasal ridge
HP:0000455	Broad nasal tip
HP:0000470	Short neck
HP:0000494	Downslanted palpebral fissures
HP:0000508	Ptosis
HP:0000518	Cataract
HP:0000520	Proptosis
HP:0000639	Nystagmus
HP:0000656	Ectropion
HP:0000668	Hypodontia
HP:0000670	Carious teeth
HP:0000682	Abnormal dental enamel morphology
HP:0000706	Eruption failure

GWAS associations

12 associations (top):

Study	Trait	p-value
GCST004029_40	Angiotensin-converting enzyme inhibitor intolerance	9.000000e-06
GCST004029_7	Angiotensin-converting enzyme inhibitor intolerance	7.000000e-06
GCST005348_63	Total body bone mineral density	2.000000e-08
GCST006268_206	Reaction time	4.000000e-12
GCST006268_508	Reaction time	2.000000e-12
GCST006268_509	Reaction time	1.000000e-09
GCST006979_116	Heel bone mineral density	7.000000e-16
GCST007856_88	Colorectal cancer or advanced adenoma	2.000000e-12
GCST008129_17	Body mass index	5.000000e-09
GCST011494_23	Daytime nap	2.000000e-11
GCST90000025_3	Appendicular lean mass	1.000000e-11
GCST90000047_106	Age at first sexual intercourse	5.000000e-08

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0005325	response to angiotensin-converting enzyme inhibitor
EFO:0008393	reaction time measurement
EFO:0009270	heel bone mineral density
EFO:0004340	body mass index
EFO:0007828	daytime rest measurement
EFO:0004980	appendicular lean mass
EFO:0009749	age at first sexual intercourse measurement

MeSH disease descriptors (20)

Descriptor	Name	Tree numbers
D006528	Carcinoma, Hepatocellular	C04.557.470.200.025.255; C04.588.274.623.160; C06.301.623.160; C06.552.697.160
D002294	Carcinoma, Squamous Cell	C04.557.470.200.400; C04.557.470.700.400
D003110	Colonic Neoplasms	C04.588.274.476.411.307.180; C06.301.371.411.307.180; C06.405.249.411.307.180; C06.405.469.158.356.180; C06.405.469.491.307.180
D003397	Craniopharyngioma	C04.557.465.625.200; C04.557.580.625.200
D018222	Desmoid Tumors	C04.557.450.565.590.340.410
D005736	Gardner Syndrome	C04.557.470.035.215.100.500; C04.588.274.476.411.307.089.393; C04.700.100.392; C06.301.371.411.307.090.500; C06.405.249.411.307.090.500; C06.405.469.158.356.090.500; C06.405.469.491.307.090.500; C06.405.469.578.249.393; C16.131.077.393; C16.320.700.100.393
D046152	Gastrointestinal Stromal Tumors	C04.557.450.565.370; C06.301.371.308; C06.405.249.308
D018197	Hepatoblastoma	C04.557.435.380
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
D007417	Intestinal Polyps	C23.300.825.411
D018285	Klatskin Tumor	C04.557.470.200.025.450.500
D009386	Neoplastic Syndromes, Hereditary	C04.700; C16.320.700
D010051	Ovarian Neoplasms	C04.588.322.455; C12.050.351.500.056.630.705; C12.050.351.937.418.685; C12.100.250.056.630.705; C12.900.418.685; C19.344.410; C19.391.630.705
D012509	Sarcoma	C04.557.450.795
D013274	Stomach Neoplasms	C04.588.274.476.767; C06.301.371.767; C06.405.249.767; C06.405.748.789
C538265	Attenuated familial adenomatous polyposis (supp.)
C562840	Breast Cancer, Familial (supp.)
C566775	Polyposis Of Gastric Fundus Without Polyposis Coli (supp.)
C562464	Polyposis, Gastric (supp.)
C538150	Syndactyly Cenani Lenz type (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL3233 (SINGLE PROTEIN), CHEMBL3885511 (PROTEIN-PROTEIN INTERACTION), CHEMBL4296093 (PROTEIN COMPLEX)

Clinical evidence (CIViC)

Drug × variant × indication: 2 predictive associations from 2 curated evidence items; also 1 prognostic.

Variant	Therapy	Indication	Effect	Level	CIViC
APC Mutation	JW55	Colon Carcinoma	Sensitivity/Response	CIViC D	EID445
APC Mutation	G007-LK	Colorectal Cancer	Sensitivity/Response	CIViC D	EID446

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

Binding affinities (BindingDB)

108 measured of 108 human assays (108 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
2-(5-pyridin-3-yl-2H-pyrazolo[3,4-b]pyridin-3-yl)-7-thiophen-2-yl-3H-imidazo[4,5-c]pyridine	IC50	1 nM	US-10071086: 1H-pyrazolo[3,4-b]pyridines and therapeutic uses thereof
5-[3-[7-(3-fluorophenyl)-3H-imidazo[4,5-c]pyridin-2-yl]-2H-pyrazolo[3,4-b]pyridin-5-yl]-N-propan-2-ylpyridin-3-amine	IC50	1.2 nM	US-10071086: 1H-pyrazolo[3,4-b]pyridines and therapeutic uses thereof
N-[5-[3-[7-(furan-3-yl)-3H-imidazo[4,5-c]pyridin-2-yl]-2H-pyrazolo[3,4-b]pyridin-5-yl]-3-pyridinyl]butanamide	IC50	3 nM	US-10071086: 1H-pyrazolo[3,4-b]pyridines and therapeutic uses thereof
5-[3-[7-(3-fluorophenyl)-3H-imidazo[4,5-c]pyridin-2-yl]-2H-pyrazolo[3,4-b]pyridin-5-yl]pyridin-3-amine	IC50	3.9 nM	US-10071086: 1H-pyrazolo[3,4-b]pyridines and therapeutic uses thereof
N-[5-[3-(7-thiophen-2-yl-3H-imidazo[4,5-c]pyridin-2-yl)-2H-pyrazolo[3,4-b]pyridin-5-yl]-3-pyridinyl]propanamide	IC50	4 nM	US-10071086: 1H-pyrazolo[3,4-b]pyridines and therapeutic uses thereof
2,2,2-trifluoro-N-[5-[3-[7-(3-fluorophenyl)-3H-imidazo[4,5-c]pyridin-2-yl]-2H-pyrazolo[3,4-b]pyridin-5-yl]-3-pyridinyl]acetamide	IC50	6 nM	US-10071086: 1H-pyrazolo[3,4-b]pyridines and therapeutic uses thereof
5-[3-[7-(3-fluorophenyl)-3H-imidazo[4,5-c]pyridin-2-yl]-2H-pyrazolo[3,4-b]pyridin-5-yl]-N,N-dimethylpyridin-3-amine	IC50	6 nM	US-10071086: 1H-pyrazolo[3,4-b]pyridines and therapeutic uses thereof
N-[5-[3-[7-(2-fluorophenyl)-3H-imidazo[4,5-c]pyridin-2-yl]-2H-pyrazolo[3,4-b]pyridin-5-yl]-3-pyridinyl]butanamide	IC50	8 nM	US-10071086: 1H-pyrazolo[3,4-b]pyridines and therapeutic uses thereof
N-[5-[3-(4-thiophen-3-yl-1H-benzimidazol-2-yl)-2H-pyrazolo[3,4-b]pyridin-5-yl]-3-pyridinyl]propanamide	IC50	10 nM	US-10071086: 1H-pyrazolo[3,4-b]pyridines and therapeutic uses thereof
N-[5-[3-[7-(3-fluorophenyl)-3H-imidazo[4,5-c]pyridin-2-yl]-2H-pyrazolo[3,4-b]pyridin-5-yl]-3-pyridinyl]cyclopropanecarboxamide	IC50	11 nM	US-10071086: 1H-pyrazolo[3,4-b]pyridines and therapeutic uses thereof
N-[5-[3-(7-pyridin-2-yl-3H-imidazo[4,5-c]pyridin-2-yl)-2H-pyrazolo[3,4-b]pyridin-5-yl]-3-pyridinyl]cyclobutanecarboxamide	IC50	12 nM	US-10071086: 1H-pyrazolo[3,4-b]pyridines and therapeutic uses thereof
5-pyridin-3-yl-3-(4-thiophen-2-yl-1H-benzimidazol-2-yl)-2H-pyrazolo[3,4-b]pyridine	IC50	12 nM	US-10071086: 1H-pyrazolo[3,4-b]pyridines and therapeutic uses thereof
1-[5-[3-[7-(3-fluorophenyl)-3H-imidazo[4,5-c]pyridin-2-yl]-2H-pyrazolo[3,4-b]pyridin-5-yl]-3-pyridinyl]-N,N-dimethylmethanamine	IC50	13 nM	US-10071086: 1H-pyrazolo[3,4-b]pyridines and therapeutic uses thereof
2-methyl-N-[5-[3-(4-thiophen-3-yl-1H-benzimidazol-2-yl)-2H-pyrazolo[3,4-b]pyridin-5-yl]-3-pyridinyl]propanamide	IC50	16 nM	US-10071086: 1H-pyrazolo[3,4-b]pyridines and therapeutic uses thereof
N-[5-[3-(4-thiophen-3-yl-1H-benzimidazol-2-yl)-2H-pyrazolo[3,4-b]pyridin-5-yl]-3-pyridinyl]cyclopropanecarboxamide	IC50	17 nM	US-10071086: 1H-pyrazolo[3,4-b]pyridines and therapeutic uses thereof
N-[5-[3-[4-(2-fluorophenyl)-1H-benzimidazol-2-yl]-2H-pyrazolo[3,4-b]pyridin-5-yl]-3-pyridinyl]butanamide	IC50	18 nM	US-10071086: 1H-pyrazolo[3,4-b]pyridines and therapeutic uses thereof
N-[5-[3-[4-(2-fluorophenyl)-1H-benzimidazol-2-yl]-2H-pyrazolo[3,4-b]pyridin-5-yl]-3-pyridinyl]cyclobutanecarboxamide	IC50	18 nM	US-10071086: 1H-pyrazolo[3,4-b]pyridines and therapeutic uses thereof
3-[4-(2-fluorophenyl)-1H-benzimidazol-2-yl]-5-pyridin-3-yl-2H-pyrazolo[3,4-b]pyridine	IC50	20 nM	US-10071086: 1H-pyrazolo[3,4-b]pyridines and therapeutic uses thereof
N-[3-fluoro-5-[2-(5-pyridin-3-yl-2H-pyrazolo[3,4-b]pyridin-3-yl)-3H-imidazo[4,5-c]pyridin-7-yl]phenyl]-N’,N’-dimethylethane-1,2-diamine	IC50	21 nM	US-10071086: 1H-pyrazolo[3,4-b]pyridines and therapeutic uses thereof
1-[5-[3-[7-(3-fluoro-5-morpholin-4-ylphenyl)-3H-imidazo[4,5-c]pyridin-2-yl]-2H-pyrazolo[3,4-b]pyridin-5-yl]-3-pyridinyl]-N,N-dimethylmethanamine	IC50	21 nM	US-10071086: 1H-pyrazolo[3,4-b]pyridines and therapeutic uses thereof
N-[5-[3-(7-thiophen-2-yl-3H-imidazo[4,5-c]pyridin-2-yl)-2H-pyrazolo[3,4-b]pyridin-5-yl]-3-pyridinyl]cyclopropanecarboxamide	IC50	22 nM	US-10071086: 1H-pyrazolo[3,4-b]pyridines and therapeutic uses thereof
1-[5-[3-[4-(3-fluorophenyl)-1H-benzimidazol-2-yl]-2H-pyrazolo[3,4-b]pyridin-5-yl]-3-pyridinyl]-N,N-dimethylmethanamine	IC50	22 nM	US-10071086: 1H-pyrazolo[3,4-b]pyridines and therapeutic uses thereof
5-[3-(1H-benzimidazol-2-yl)-2H-pyrazolo[3,4-b]pyridin-5-yl]-N,N-dimethylpyridin-3-amine	IC50	27 nM	US-10071086: 1H-pyrazolo[3,4-b]pyridines and therapeutic uses thereof
N-propan-2-yl-5-[3-(4-pyridin-4-yl-1H-benzimidazol-2-yl)-2H-pyrazolo[3,4-b]pyridin-5-yl]pyridin-3-amine	IC50	30 nM	US-10071086: 1H-pyrazolo[3,4-b]pyridines and therapeutic uses thereof
N-[[3-[2-[5-[5-[(dimethylamino)methyl]-3-pyridinyl]-2H-pyrazolo[3,4-b]pyridin-3-yl]-3H-imidazo[4,5-c]pyridin-7-yl]-5-fluorophenyl]methyl]methanesulfonamide	IC50	32 nM	US-10071086: 1H-pyrazolo[3,4-b]pyridines and therapeutic uses thereof
N,N-dimethyl-1-[5-[3-(4-thiophen-3-yl-1H-benzimidazol-2-yl)-2H-pyrazolo[3,4-b]pyridin-5-yl]-3-pyridinyl]methanamine	IC50	32 nM	US-10071086: 1H-pyrazolo[3,4-b]pyridines and therapeutic uses thereof
5-[3-[4-(3-fluorophenyl)-1H-benzimidazol-2-yl]-2H-pyrazolo[3,4-b]pyridin-5-yl]-N-propan-2-ylpyridin-3-amine	IC50	33 nM	US-10071086: 1H-pyrazolo[3,4-b]pyridines and therapeutic uses thereof
5-[3-(4-pyridin-4-yl-1H-benzimidazol-2-yl)-2H-pyrazolo[3,4-b]pyridin-5-yl]pyridin-3-amine	IC50	34 nM	US-10071086: 1H-pyrazolo[3,4-b]pyridines and therapeutic uses thereof
N,N-dimethyl-1-[5-[3-(4-pyridin-3-yl-1H-benzimidazol-2-yl)-2H-pyrazolo[3,4-b]pyridin-5-yl]-3-pyridinyl]methanamine	IC50	36 nM	US-10071086: 1H-pyrazolo[3,4-b]pyridines and therapeutic uses thereof
N-[5-[3-[7-(3-fluorophenyl)-3H-imidazo[4,5-c]pyridin-2-yl]-2H-pyrazolo[3,4-b]pyridin-5-yl]-3-pyridinyl]-2,2-dimethylpropanamide	IC50	38 nM	US-10071086: 1H-pyrazolo[3,4-b]pyridines and therapeutic uses thereof
N-[5-[3-[4-(4-methylimidazol-1-yl)-1H-benzimidazol-2-yl]-2H-pyrazolo[3,4-b]pyridin-5-yl]-3-pyridinyl]cyclohexanecarboxamide	IC50	39 nM	US-10071086: 1H-pyrazolo[3,4-b]pyridines and therapeutic uses thereof
N,N-dimethyl-1-[5-[3-(7-thiophen-2-yl-3H-imidazo[4,5-c]pyridin-2-yl)-2H-pyrazolo[3,4-b]pyridin-5-yl]-3-pyridinyl]methanamine	IC50	48 nM	US-10071086: 1H-pyrazolo[3,4-b]pyridines and therapeutic uses thereof
N-[5-[3-[4-(4-fluorophenyl)-1H-benzimidazol-2-yl]-2H-pyrazolo[3,4-b]pyridin-5-yl]-3-pyridinyl]cyclopropanecarboxamide	IC50	48 nM	US-10071086: 1H-pyrazolo[3,4-b]pyridines and therapeutic uses thereof
5-[5-[(3,3-difluoropyrrolidin-1-yl)methyl]-3-pyridinyl]-3-[4-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-2H-pyrazolo[3,4-b]pyridine	IC50	48 nM	US-10071086: 1H-pyrazolo[3,4-b]pyridines and therapeutic uses thereof
N-[5-[3-[4-(furan-3-yl)-1H-benzimidazol-2-yl]-2H-pyrazolo[3,4-b]pyridin-5-yl]-3-pyridinyl]-2,2-dimethylpropanamide	IC50	50 nM	US-10071086: 1H-pyrazolo[3,4-b]pyridines and therapeutic uses thereof
N-[5-[3-[7-(furan-3-yl)-1H-imidazo[4,5-c]pyridin-2-yl]-7H-pyrazolo[3,4-b]pyridin-5-yl]-3-pyridinyl]benzamide	IC50	51 nM	US-10071086: 1H-pyrazolo[3,4-b]pyridines and therapeutic uses thereof
N-[5-[3-[4-(3-fluorophenyl)-1H-benzimidazol-2-yl]-2H-pyrazolo[3,4-b]pyridin-5-yl]-3-pyridinyl]pentanamide	IC50	53 nM	US-10071086: 1H-pyrazolo[3,4-b]pyridines and therapeutic uses thereof
N,N-dimethyl-5-[3-(7-thiophen-3-yl-3H-imidazo[4,5-c]pyridin-2-yl)-2H-pyrazolo[3,4-b]pyridin-5-yl]pyridin-3-amine	IC50	56 nM	US-10071086: 1H-pyrazolo[3,4-b]pyridines and therapeutic uses thereof
N,N-dimethyl-1-[5-[3-(7-thiophen-3-yl-3H-imidazo[4,5-c]pyridin-2-yl)-2H-pyrazolo[3,4-b]pyridin-5-yl]-3-pyridinyl]methanamine	IC50	57 nM	US-10071086: 1H-pyrazolo[3,4-b]pyridines and therapeutic uses thereof
5-[3-(3H-imidazo[4,5-c]pyridin-2-yl)-2H-pyrazolo[3,4-b]pyridin-5-yl]-N-propan-2-ylpyridin-3-amine	IC50	58 nM	US-10071086: 1H-pyrazolo[3,4-b]pyridines and therapeutic uses thereof
N-[5-[3-[4-(furan-3-yl)-1H-benzimidazol-2-yl]-2H-pyrazolo[3,4-b]pyridin-5-yl]-3-pyridinyl]butanamide	IC50	63 nM	US-10071086: 1H-pyrazolo[3,4-b]pyridines and therapeutic uses thereof
N-[5-[3-[7-(furan-3-yl)-3H-imidazo[4,5-c]pyridin-2-yl]-2H-pyrazolo[3,4-b]pyridin-5-yl]-3-pyridinyl]-2,2-dimethylpropanamide	IC50	70 nM	US-10071086: 1H-pyrazolo[3,4-b]pyridines and therapeutic uses thereof
N-[5-[3-[7-(4-fluorophenyl)-1H-benzimidazol-2-yl]-7H-pyrazolo[3,4-b]pyridin-5-yl]-3-pyridinyl]benzamide	IC50	82 nM	US-10071086: 1H-pyrazolo[3,4-b]pyridines and therapeutic uses thereof
5-[5-(piperidin-1-ylmethyl)-3-pyridinyl]-3-(4-thiophen-3-yl-1H-benzimidazol-2-yl)-2H-pyrazolo[3,4-b]pyridine	IC50	82 nM	US-10071086: 1H-pyrazolo[3,4-b]pyridines and therapeutic uses thereof
N-[5-[3-[7-(4-fluorophenyl)-3H-imidazo[4,5-c]pyridin-2-yl]-2H-pyrazolo[3,4-b]pyridin-5-yl]-3-pyridinyl]-2-phenylacetamide	IC50	90 nM	US-10071086: 1H-pyrazolo[3,4-b]pyridines and therapeutic uses thereof
N-[5-[3-[4-(3-fluorophenyl)-1H-benzimidazol-2-yl]-2H-pyrazolo[3,4-b]pyridin-5-yl]-3-pyridinyl]cyclopentanecarboxamide	IC50	90 nM	US-10071086: 1H-pyrazolo[3,4-b]pyridines and therapeutic uses thereof
N-[[5-[3-[4-(3-fluorophenyl)-1H-benzimidazol-2-yl]-2H-pyrazolo[3,4-b]pyridin-5-yl]-3-pyridinyl]methyl]ethanamine	IC50	97 nM	US-10071086: 1H-pyrazolo[3,4-b]pyridines and therapeutic uses thereof
1-cyclopentyl-N-[[5-[3-(7-thiophen-2-yl-3H-imidazo[4,5-c]pyridin-2-yl)-2H-pyrazolo[3,4-b]pyridin-5-yl]-3-pyridinyl]methyl]methanamine	IC50	98 nM	US-10071086: 1H-pyrazolo[3,4-b]pyridines and therapeutic uses thereof
3-[7-[3-fluoro-5-(4-methylpiperazin-1-yl)phenyl]-3H-imidazo[4,5-c]pyridin-2-yl]-5-pyridin-3-yl-2H-pyrazolo[3,4-b]pyridine	IC50	99 nM	US-10071086: 1H-pyrazolo[3,4-b]pyridines and therapeutic uses thereof
5-(4-methyl-3-pyridinyl)-3-(4-pyridin-4-yl-1H-benzimidazol-2-yl)-2H-pyrazolo[3,4-b]pyridine	IC50	110 nM	US-10071086: 1H-pyrazolo[3,4-b]pyridines and therapeutic uses thereof

ChEMBL bioactivities

68 potent at pChembl≥5 of 93 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.92	Kd	12	nM	CHEMBL4164672
7.82	Ki	15	nM	CHEMBL5288446
7.82	Ki	15	nM	CHEMBL4163133
7.44	Kd	36	nM	CHEMBL5287183
6.92	Ki	120	nM	CHEMBL5280732
6.75	IC50	180	nM	CHEMBL4640669
6.68	Kd	210	nM	CHEMBL4164672
6.68	Kd	210	nM	CHEMBL4171050
6.66	Kd	220	nM	CHEMBL4164672
6.60	Kd	250	nM	CHEMBL4164672
6.37	Kd	430	nM	CHEMBL4171050
6.24	Kd	570	nM	CHEMBL4163133
6.24	IC50	570	nM	CHEMBL5288446
6.21	Kd	620	nM	CHEMBL4160474
6.08	Kd	840	nM	CHEMBL4162624
6.06	IC50	880	nM	CHEMBL4641941
5.96	Kd	1090	nM	CHEMBL4171050
5.96	IC50	1090	nM	CHEMBL5280732
5.94	IC50	1160	nM	CHEMBL4635945
5.90	Kd	1260	nM	CHEMBL4175576
5.89	Kd	1300	nM	CHEMBL4168374
5.87	IC50	1340	nM	CHEMBL4644650
5.86	IC50	1370	nM	CHEMBL4647867
5.85	IC50	1410	nM	CHEMBL4637789
5.82	Kd	1530	nM	CHEMBL4176124
5.82	Kd	1510	nM	CHEMBL4174887
5.75	Kd	1800	nM	CHEMBL4171050
5.75	Kd	1780	nM	CHEMBL4168793
5.74	Kd	1820	nM	CHEMBL4163905
5.71	Kd	1940	nM	CHEMBL4163850
5.71	IC50	1930	nM	CHEMBL4647287
5.70	Kd	2010	nM	CHEMBL4172555
5.63	IC50	2340	nM	CHEMBL4647225
5.62	Ki	2410	nM	CHEMBL5289275
5.61	IC50	2460	nM	CHEMBL4632529
5.53	Kd	2950	nM	CHEMBL4161816
5.52	Kd	3020	nM	CHEMBL4174376
5.51	Ki	3120	nM	CHEMBL5289169
5.48	Kd	3300	nM	CHEMBL4170559
5.45	IC50	3580	nM	CHEMBL4642657
5.44	Kd	3640	nM	CHEMBL4176650
5.42	Kd	3850	nM	CHEMBL4163710
5.42	Ki	3800	nM	CHEMBL5282293
5.40	Kd	3960	nM	CHEMBL4167760
5.40	Kd	4010	nM	CHEMBL4167355
5.39	Kd	4070	nM	CHEMBL4171789
5.37	Kd	4290	nM	CHEMBL4172297
5.36	Kd	4360	nM	CHEMBL4174568
5.36	IC50	4350	nM	CHEMBL4632800
5.31	IC50	4880	nM	CHEMBL4646958

PubChem BioAssay actives

66 with measured affinity, of 121 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(4S)-5-amino-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-4-carboxy-2-[[2-[[(2S)-2-(phenylmethoxycarbonylamino)propanoyl]amino]acetyl]amino]butanoyl]amino]-3-hydroxypropanoyl]amino]-4-methylpentanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-5-oxopentanoic acid	1357075: Binding affinity to APC (unknown origin) at 30 degC by ITC method	kd	0.0120	uM
(4S)-5-amino-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-4-carboxy-2-[[2-[[(2S)-2-(phenylmethoxycarbonylamino)propanoyl]amino]acetyl]amino]butanoyl]amino]propanoyl]amino]-3-cyclopentylpropanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-5-oxopentanoic acid	1928058: Binding affinity to APC (unknown origin) assessed as inhibition constant by ITC analysis	ki	0.0150	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-4-carboxy-2-[[2-[[(2S)-2-(phenylmethoxycarbonylamino)propanoyl]amino]acetyl]amino]butanoyl]amino]propanoyl]amino]-3-cyclopentylpropanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]pentanedioic acid	1923765: Inhibition of APC (303 to 739 residues) (unknown origin) assessed as inhibition constant preincubated for 60 mins followed by substrate addition and measured after 60 mins using Ac-GGGGEQLAINELISDGK-FITC as substrate by fluorescence polarization assay	ki	0.0150	uM
(4S)-4-[[2-[(2-acetamidoacetyl)amino]acetyl]amino]-5-[[(2S)-5-amino-1-[[(2S)-1-[[1-[(1-amino-3-methyl-1-oxopentan-2-yl)amino]-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-5-oxopentanoic acid	1928059: Binding affinity to APC (unknown origin) assessed as dissociation constant by ITC analysis	kd	0.0360	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-4-carboxy-2-[[2-[[(2S)-2-(phenylmethoxycarbonylamino)propanoyl]amino]acetyl]amino]butanoyl]amino]propanoyl]amino]-4-methylpentanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]pentanedioic acid	1923765: Inhibition of APC (303 to 739 residues) (unknown origin) assessed as inhibition constant preincubated for 60 mins followed by substrate addition and measured after 60 mins using Ac-GGGGEQLAINELISDGK-FITC as substrate by fluorescence polarization assay	ki	0.1200	uM
[4-[5-(4-fluorophenyl)-3-naphthalen-1-yl-3,4-dihydropyrazol-2-yl]phenyl]-morpholin-4-ylmethanone	1649936: Binding affinity to APC (unknown origin) assessed as inhibition of APC-Asef protein-protein interaction after 2 hrs by fluorescence polarization immunoassay	ic50	0.1800	uM
(4S)-5-amino-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-4-carboxy-2-[[2-[[(2S)-2-(phenylmethoxycarbonylamino)propanoyl]amino]acetyl]amino]butanoyl]amino]propanoyl]amino]-4-methylpentanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-5-oxopentanoic acid	1357075: Binding affinity to APC (unknown origin) at 30 degC by ITC method	kd	0.2100	uM
(4S)-5-amino-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-4-carboxy-2-[[2-[[(2S)-2-(phenylmethoxycarbonylamino)propanoyl]amino]acetyl]amino]butanoyl]amino]-3-hydroxypropanoyl]amino]-3-cyclopentylpropanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-5-oxopentanoic acid	1357066: Binding affinity to APC protein (303 to 739 residues) (unknown origin) incubated for 60 mins followed by probe addition and measured after 60 mins by competitive fluorescence polarization assay	kd	0.6200	uM
(4S)-5-amino-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-4-carboxy-2-[[2-[[(2S)-2-(phenylmethoxycarbonylamino)propanoyl]amino]acetyl]amino]butanoyl]amino]-3-hydroxypropanoyl]amino]-5-methylhexanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-5-oxopentanoic acid	1357066: Binding affinity to APC protein (303 to 739 residues) (unknown origin) incubated for 60 mins followed by probe addition and measured after 60 mins by competitive fluorescence polarization assay	kd	0.8400	uM
[4-[5-(4-fluorophenyl)-3-naphthalen-2-yl-3,4-dihydropyrazol-2-yl]phenyl]-morpholin-4-ylmethanone	1649936: Binding affinity to APC (unknown origin) assessed as inhibition of APC-Asef protein-protein interaction after 2 hrs by fluorescence polarization immunoassay	ic50	0.8800	uM
[4-[5-(4-chlorophenyl)-3-naphthalen-2-yl-3,4-dihydropyrazol-2-yl]phenyl]-morpholin-4-ylmethanone	1649936: Binding affinity to APC (unknown origin) assessed as inhibition of APC-Asef protein-protein interaction after 2 hrs by fluorescence polarization immunoassay	ic50	1.1600	uM
(4S)-5-amino-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-4-carboxy-2-[[2-[[(2S)-2-(phenylmethoxycarbonylamino)propanoyl]amino]acetyl]amino]butanoyl]amino]-3-hydroxypropanoyl]amino]-3-cyclopropylpropanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-5-oxopentanoic acid	1357066: Binding affinity to APC protein (303 to 739 residues) (unknown origin) incubated for 60 mins followed by probe addition and measured after 60 mins by competitive fluorescence polarization assay	kd	1.2600	uM
(4S)-5-amino-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-4-carboxy-2-[[2-[[(2S)-2-(phenylmethoxycarbonylamino)propanoyl]amino]acetyl]amino]butanoyl]amino]-3-hydroxypropanoyl]amino]-3-cyclohexylpropanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-5-oxopentanoic acid	1357066: Binding affinity to APC protein (303 to 739 residues) (unknown origin) incubated for 60 mins followed by probe addition and measured after 60 mins by competitive fluorescence polarization assay	kd	1.3000	uM
[4-[5-(3-chlorophenyl)-3-naphthalen-1-yl-3,4-dihydropyrazol-2-yl]phenyl]-morpholin-4-ylmethanone	1649936: Binding affinity to APC (unknown origin) assessed as inhibition of APC-Asef protein-protein interaction after 2 hrs by fluorescence polarization immunoassay	ic50	1.3400	uM
[4-[5-(4-bromophenyl)-3-naphthalen-1-yl-3,4-dihydropyrazol-2-yl]phenyl]-morpholin-4-ylmethanone	1649936: Binding affinity to APC (unknown origin) assessed as inhibition of APC-Asef protein-protein interaction after 2 hrs by fluorescence polarization immunoassay	ic50	1.3700	uM
morpholin-4-yl-[4-(3-naphthalen-1-yl-5-phenyl-3,4-dihydropyrazol-2-yl)phenyl]methanone	1649936: Binding affinity to APC (unknown origin) assessed as inhibition of APC-Asef protein-protein interaction after 2 hrs by fluorescence polarization immunoassay	ic50	1.4100	uM
(4S)-5-amino-4-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S)-4-carboxy-2-[[2-[[(2S)-2-(phenylmethoxycarbonylamino)propanoyl]amino]acetyl]amino]butanoyl]amino]-3-sulfanylpropanoyl]amino]-4-methylpentanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-5-oxopentanoic acid	1357066: Binding affinity to APC protein (303 to 739 residues) (unknown origin) incubated for 60 mins followed by probe addition and measured after 60 mins by competitive fluorescence polarization assay	kd	1.5100	uM
(4S)-5-amino-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-4-carboxy-2-[[2-[[(2S)-2-(phenylmethoxycarbonylamino)propanoyl]amino]acetyl]amino]butanoyl]amino]-3-hydroxypropanoyl]amino]-3-cyclobutylpropanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-5-oxopentanoic acid	1357066: Binding affinity to APC protein (303 to 739 residues) (unknown origin) incubated for 60 mins followed by probe addition and measured after 60 mins by competitive fluorescence polarization assay	kd	1.5300	uM
(4S)-5-amino-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-4-carboxy-2-[[2-[[(2S)-2-(phenylmethoxycarbonylamino)propanoyl]amino]acetyl]amino]butanoyl]amino]-3-hydroxypropanoyl]amino]-4,4-dimethylpentanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-5-oxopentanoic acid	1357066: Binding affinity to APC protein (303 to 739 residues) (unknown origin) incubated for 60 mins followed by probe addition and measured after 60 mins by competitive fluorescence polarization assay	kd	1.7800	uM
(4S)-5-amino-4-[[(2S)-2-[[(2S)-4-bromo-2-[[(2S)-2-[[(2S)-4-carboxy-2-[[2-[[(2S)-2-(phenylmethoxycarbonylamino)propanoyl]amino]acetyl]amino]butanoyl]amino]-3-hydroxypropanoyl]amino]pent-4-enoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-5-oxopentanoic acid	1357066: Binding affinity to APC protein (303 to 739 residues) (unknown origin) incubated for 60 mins followed by probe addition and measured after 60 mins by competitive fluorescence polarization assay	kd	1.8200	uM
[4-[5-(3,4-dichlorophenyl)-3-naphthalen-2-yl-3,4-dihydropyrazol-2-yl]phenyl]-morpholin-4-ylmethanone	1649936: Binding affinity to APC (unknown origin) assessed as inhibition of APC-Asef protein-protein interaction after 2 hrs by fluorescence polarization immunoassay	ic50	1.9300	uM
(4S)-5-amino-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-4-carboxy-2-[[2-[[(2S)-2-(phenylmethoxycarbonylamino)propanoyl]amino]acetyl]amino]butanoyl]amino]-3-hydroxypropanoyl]amino]-3-cycloheptylpropanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-5-oxopentanoic acid	1357066: Binding affinity to APC protein (303 to 739 residues) (unknown origin) incubated for 60 mins followed by probe addition and measured after 60 mins by competitive fluorescence polarization assay	kd	1.9400	uM
(4S)-5-amino-4-[[(2S)-2-[[(2S)-2-[[(2S,3S)-2-[[(2S)-4-carboxy-2-[[2-[[(2S)-2-(phenylmethoxycarbonylamino)propanoyl]amino]acetyl]amino]butanoyl]amino]-3-hydroxybutanoyl]amino]-4-methylpentanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-5-oxopentanoic acid	1357066: Binding affinity to APC protein (303 to 739 residues) (unknown origin) incubated for 60 mins followed by probe addition and measured after 60 mins by competitive fluorescence polarization assay	kd	2.0100	uM
[4-[5-(4-bromophenyl)-3-naphthalen-2-yl-3,4-dihydropyrazol-2-yl]phenyl]-morpholin-4-ylmethanone	1649936: Binding affinity to APC (unknown origin) assessed as inhibition of APC-Asef protein-protein interaction after 2 hrs by fluorescence polarization immunoassay	ic50	2.3400	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-acetamidopropanoyl]amino]acetyl]amino]-4-carboxybutanoyl]amino]propanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]butanedioic acid	1923765: Inhibition of APC (303 to 739 residues) (unknown origin) assessed as inhibition constant preincubated for 60 mins followed by substrate addition and measured after 60 mins using Ac-GGGGEQLAINELISDGK-FITC as substrate by fluorescence polarization assay	ki	2.4100	uM
morpholin-4-yl-[4-(3-naphthalen-2-yl-5-phenyl-3,4-dihydropyrazol-2-yl)phenyl]methanone	1649936: Binding affinity to APC (unknown origin) assessed as inhibition of APC-Asef protein-protein interaction after 2 hrs by fluorescence polarization immunoassay	ic50	2.4600	uM
(4S)-5-amino-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-4-carboxy-2-[[2-[[(2S)-2-(phenylmethoxycarbonylamino)propanoyl]amino]acetyl]amino]butanoyl]amino]-3-hydroxypropanoyl]amino]-2-cyclohexylacetyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-5-oxopentanoic acid	1357066: Binding affinity to APC protein (303 to 739 residues) (unknown origin) incubated for 60 mins followed by probe addition and measured after 60 mins by competitive fluorescence polarization assay	kd	2.9500	uM
(4S)-5-amino-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-4-carboxy-2-[[2-[[(2S)-2-(phenylmethoxycarbonylamino)propanoyl]amino]acetyl]amino]butanoyl]amino]-3-hydroxypropanoyl]amino]decanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-5-oxopentanoic acid	1357066: Binding affinity to APC protein (303 to 739 residues) (unknown origin) incubated for 60 mins followed by probe addition and measured after 60 mins by competitive fluorescence polarization assay	kd	3.0200	uM
(4S)-4-[[2-[(2-acetamidoacetyl)amino]acetyl]amino]-5-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(1S)-1-carboxy-2-(1H-indol-3-yl)ethyl]amino]-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-5-oxopentanoic acid	1923765: Inhibition of APC (303 to 739 residues) (unknown origin) assessed as inhibition constant preincubated for 60 mins followed by substrate addition and measured after 60 mins using Ac-GGGGEQLAINELISDGK-FITC as substrate by fluorescence polarization assay	ki	3.1200	uM
(4S)-5-amino-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-4-carboxy-2-[[2-[[(2S)-2-(phenylmethoxycarbonylamino)propanoyl]amino]acetyl]amino]butanoyl]amino]-3-hydroxypropanoyl]amino]-4-methylsulfanylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-5-oxopentanoic acid	1357066: Binding affinity to APC protein (303 to 739 residues) (unknown origin) incubated for 60 mins followed by probe addition and measured after 60 mins by competitive fluorescence polarization assay	kd	3.3000	uM
[4-[5-(3-bromophenyl)-3-naphthalen-1-yl-3,4-dihydropyrazol-2-yl]phenyl]-morpholin-4-ylmethanone	1649936: Binding affinity to APC (unknown origin) assessed as inhibition of APC-Asef protein-protein interaction after 2 hrs by fluorescence polarization immunoassay	ic50	3.5800	uM
(4S)-5-amino-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-4-carboxy-2-[[2-[[(2S)-2-(phenylmethoxycarbonylamino)propanoyl]amino]acetyl]amino]butanoyl]amino]-3-hydroxypropanoyl]amino]-4-methylpent-4-enoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-5-oxopentanoic acid	1357066: Binding affinity to APC protein (303 to 739 residues) (unknown origin) incubated for 60 mins followed by probe addition and measured after 60 mins by competitive fluorescence polarization assay	kd	3.6400	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[(2-acetamidoacetyl)amino]acetyl]amino]-4-carboxybutanoyl]amino]propanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]butanedioic acid	1923765: Inhibition of APC (303 to 739 residues) (unknown origin) assessed as inhibition constant preincubated for 60 mins followed by substrate addition and measured after 60 mins using Ac-GGGGEQLAINELISDGK-FITC as substrate by fluorescence polarization assay	ki	3.8000	uM
(4S)-5-amino-4-[[(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-4-carboxy-2-[[2-[[(2S)-2-(phenylmethoxycarbonylamino)propanoyl]amino]acetyl]amino]butanoyl]amino]-3-hydroxypropanoyl]amino]-3-methylpentanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-5-oxopentanoic acid	1357066: Binding affinity to APC protein (303 to 739 residues) (unknown origin) incubated for 60 mins followed by probe addition and measured after 60 mins by competitive fluorescence polarization assay	kd	3.8500	uM
(4S)-5-amino-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-4-carboxy-2-[[2-[[(2S)-2-(phenylmethoxycarbonylamino)propanoyl]amino]acetyl]amino]butanoyl]amino]-3-hydroxypropanoyl]amino]-3-naphthalen-2-ylpropanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-5-oxopentanoic acid	1357066: Binding affinity to APC protein (303 to 739 residues) (unknown origin) incubated for 60 mins followed by probe addition and measured after 60 mins by competitive fluorescence polarization assay	kd	3.9600	uM
(4S)-5-amino-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-4-carboxy-2-[[2-[[(2S)-2-(phenylmethoxycarbonylamino)propanoyl]amino]acetyl]amino]butanoyl]amino]-3-hydroxypropanoyl]amino]-3-thiophen-2-ylpropanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-5-oxopentanoic acid	1357066: Binding affinity to APC protein (303 to 739 residues) (unknown origin) incubated for 60 mins followed by probe addition and measured after 60 mins by competitive fluorescence polarization assay	kd	4.0100	uM
(4S)-5-amino-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-4-carboxy-2-[[2-[[(2S)-2-(phenylmethoxycarbonylamino)propanoyl]amino]acetyl]amino]butanoyl]amino]-3-hydroxypropanoyl]amino]-2-cyclopentylacetyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-5-oxopentanoic acid	1357066: Binding affinity to APC protein (303 to 739 residues) (unknown origin) incubated for 60 mins followed by probe addition and measured after 60 mins by competitive fluorescence polarization assay	kd	4.0700	uM
(4S)-5-amino-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-4-carboxy-2-[[2-[[(2S)-2-(phenylmethoxycarbonylamino)propanoyl]amino]acetyl]amino]butanoyl]amino]-3-hydroxypropanoyl]amino]-2-phenylacetyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-5-oxopentanoic acid	1357066: Binding affinity to APC protein (303 to 739 residues) (unknown origin) incubated for 60 mins followed by probe addition and measured after 60 mins by competitive fluorescence polarization assay	kd	4.2900	uM
[4-[5-(3-methylphenyl)-3-naphthalen-2-yl-3,4-dihydropyrazol-2-yl]phenyl]-morpholin-4-ylmethanone	1649936: Binding affinity to APC (unknown origin) assessed as inhibition of APC-Asef protein-protein interaction after 2 hrs by fluorescence polarization immunoassay	ic50	4.3500	uM
(4S)-5-amino-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-4-carboxy-2-[[2-[[(2S)-2-(phenylmethoxycarbonylamino)propanoyl]amino]acetyl]amino]butanoyl]amino]-3-hydroxypropanoyl]amino]-3-phenylpropanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-5-oxopentanoic acid	1357066: Binding affinity to APC protein (303 to 739 residues) (unknown origin) incubated for 60 mins followed by probe addition and measured after 60 mins by competitive fluorescence polarization assay	kd	4.3600	uM
[4-[5-(3-chlorophenyl)-3-naphthalen-2-yl-3,4-dihydropyrazol-2-yl]phenyl]-morpholin-4-ylmethanone	1649936: Binding affinity to APC (unknown origin) assessed as inhibition of APC-Asef protein-protein interaction after 2 hrs by fluorescence polarization immunoassay	ic50	4.8800	uM
(4S)-5-amino-4-[[(2S)-2-[[(2S)-3-(5-bromothiophen-2-yl)-2-[[(2S)-2-[[(2S)-4-carboxy-2-[[2-[[(2S)-2-(phenylmethoxycarbonylamino)propanoyl]amino]acetyl]amino]butanoyl]amino]-3-hydroxypropanoyl]amino]propanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-5-oxopentanoic acid	1357066: Binding affinity to APC protein (303 to 739 residues) (unknown origin) incubated for 60 mins followed by probe addition and measured after 60 mins by competitive fluorescence polarization assay	kd	5.0000	uM
(4S)-5-amino-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-4-carboxy-2-[[2-[[(2S)-2-(phenylmethoxycarbonylamino)propanoyl]amino]acetyl]amino]butanoyl]amino]-3-hydroxypropanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-5-oxopentanoic acid	1357066: Binding affinity to APC protein (303 to 739 residues) (unknown origin) incubated for 60 mins followed by probe addition and measured after 60 mins by competitive fluorescence polarization assay	kd	5.0700	uM
(4S)-5-amino-4-[[(2S)-2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-4-carboxy-2-[[2-[[(2S)-2-(phenylmethoxycarbonylamino)propanoyl]amino]acetyl]amino]butanoyl]amino]-4-oxobutanoyl]amino]-4-methylpentanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-5-oxopentanoic acid	1357066: Binding affinity to APC protein (303 to 739 residues) (unknown origin) incubated for 60 mins followed by probe addition and measured after 60 mins by competitive fluorescence polarization assay	kd	5.1900	uM
(4S)-5-amino-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-4-carboxy-2-[[2-[[(2S)-2-(phenylmethoxycarbonylamino)propanoyl]amino]acetyl]amino]butanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-methylpentanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-5-oxopentanoic acid	1357066: Binding affinity to APC protein (303 to 739 residues) (unknown origin) incubated for 60 mins followed by probe addition and measured after 60 mins by competitive fluorescence polarization assay	kd	5.4600	uM
(4S)-5-amino-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-4-carboxy-2-[[2-[[(2S)-2-(phenylmethoxycarbonylamino)propanoyl]amino]acetyl]amino]butanoyl]amino]-3-hydroxypropanoyl]amino]-4-methylsulfonylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-5-oxopentanoic acid	1357066: Binding affinity to APC protein (303 to 739 residues) (unknown origin) incubated for 60 mins followed by probe addition and measured after 60 mins by competitive fluorescence polarization assay	kd	5.7300	uM
[4-[5-(3-methylphenyl)-3-naphthalen-1-yl-3,4-dihydropyrazol-2-yl]phenyl]-morpholin-4-ylmethanone	1649936: Binding affinity to APC (unknown origin) assessed as inhibition of APC-Asef protein-protein interaction after 2 hrs by fluorescence polarization immunoassay	ic50	5.7400	uM
(4S)-5-amino-4-[[(2S)-2-[[(2S)-2-[[(2S)-3-carboxy-2-[[(2S)-4-carboxy-2-[[2-[[(2S)-2-(phenylmethoxycarbonylamino)propanoyl]amino]acetyl]amino]butanoyl]amino]propanoyl]amino]-4-methylpentanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-5-oxopentanoic acid	1357066: Binding affinity to APC protein (303 to 739 residues) (unknown origin) incubated for 60 mins followed by probe addition and measured after 60 mins by competitive fluorescence polarization assay	kd	6.3500	uM
(4S)-5-amino-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-4-carboxy-2-[[2-[[(2S)-2-(phenylmethoxycarbonylamino)propanoyl]amino]acetyl]amino]butanoyl]amino]-3-hydroxypropanoyl]amino]-3-thiophen-3-ylpropanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-5-oxopentanoic acid	1357066: Binding affinity to APC protein (303 to 739 residues) (unknown origin) incubated for 60 mins followed by probe addition and measured after 60 mins by competitive fluorescence polarization assay	kd	6.8600	uM
(4S)-5-amino-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-4-carboxy-2-[[2-[[(2S)-2-(phenylmethoxycarbonylamino)propanoyl]amino]acetyl]amino]butanoyl]amino]-3-hydroxypropanoyl]amino]-3-(furan-2-yl)propanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-5-oxopentanoic acid	1357066: Binding affinity to APC protein (303 to 739 residues) (unknown origin) incubated for 60 mins followed by probe addition and measured after 60 mins by competitive fluorescence polarization assay	kd	6.9500	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
trichostatin A	affects cotreatment, decreases expression, increases expression	3
Tretinoin	decreases expression, increases expression	3
oxybenzone	decreases expression, increases expression	2
Decitabine	affects methylation, decreases methylation	2
Benzo(a)pyrene	affects methylation, decreases methylation, increases methylation	2
Quercetin	increases expression, decreases expression	2
Tobacco Smoke Pollution	increases expression, increases methylation	2
Particulate Matter	decreases expression, increases methylation	2
FR900359	affects phosphorylation	1
methylmercuric chloride	decreases expression	1
uranyl acetate	affects expression	1
bisphenol A	decreases methylation	1
arsenite	affects binding, decreases reaction	1
sodium arsenite	increases abundance, increases expression	1
cobaltous chloride	increases expression	1
butyraldehyde	decreases expression	1
manganese chloride	decreases expression, increases methylation	1
benzo(e)pyrene	increases methylation	1
4-hydroxy-2-nonenal	decreases expression	1
coumarin	decreases phosphorylation	1
tamibarotene	decreases expression	1
16-hydroxycleroda-3,13(14)-dien-15,16-olide	decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	decreases expression	1
dorsomorphin	decreases expression, affects cotreatment	1
CGP049090	affects binding, decreases reaction	1
PKF115-584	affects binding, decreases reaction	1
bisphenol S	increases methylation	1

ChEMBL screening assays

24 unique, capped per target: 24 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4151963	Binding	Binding affinity to APC protein (303 to 739 residues) (unknown origin) incubated for 60 mins followed by probe addition and measured after 60 mins by competitive fluorescence polarization assay	Rational Design and Structure Validation of a Novel Peptide Inhibitor of the Adenomatous-Polyposis-Coli (APC)-Rho-Guanine-Nucleotide-Exchange-Factor-4 (Asef) Interaction. — J Med Chem

Cellosaurus cell lines

615 cell lines: 563 cancer cell line, 19 transformed cell line, 17 finite cell line, 5 induced pluripotent stem cell, 5 spontaneously immortalized cell line, 4 telomerase immortalized cell line, 1 undefined cell line type, 1 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_0025	Caco-2	Cancer cell line	Male
CVCL_0039	SK-MEL-30	Cancer cell line	Male
CVCL_0144	ARO	Cancer cell line	Female
CVCL_0218	COLO 205	Cancer cell line	Male
CVCL_0219	COLO 320DM	Cancer cell line	Female
CVCL_0220	COLO 320HSR	Cancer cell line	Female
CVCL_0232	Caco-2/15	Cancer cell line	Male
CVCL_0233	Caco-2/TC-7	Cancer cell line	Male
CVCL_0248	DLD-1	Cancer cell line	Male
CVCL_0271	GEO	Cancer cell line	Sex unspecified

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00140894	PHASE4	TERMINATED	A Study of Rofecoxib in Familial Adenomatous Polyposis (FAP) (0966-205)(TERMINATED)
NCT03144206	PHASE4	ACTIVE_NOT_RECRUITING	Hyperbaric Oxygen Therapy for Soft Tissue Sarcoma Pilot Study
NCT03244020	PHASE4	ENROLLING_BY_INVITATION	LMWH vs Aspirin for VTE Prophylaxis in Orthopaedic Oncology
NCT04033081	PHASE4	ACTIVE_NOT_RECRUITING	Registry of Sarcoma Patients Treated With Permanently Implantable LDR CivaSheet®
NCT00365508	PHASE4	COMPLETED	Counseling and Nicotine Replacement Therapy in Helping Adult Smokers Quit Smoking
NCT00558155	PHASE4	COMPLETED	The Impact of Immunostimulating Nutrition on the Outcome of Surgery
NCT00576940	PHASE4	COMPLETED	Standard and Immunostimulating Enteral Nutrition in Surgical Patients
NCT00666978	PHASE4	COMPLETED	Health Education Counseling With or Without Bupropion in Helping African Americans Stop Smoking
NCT01038154	PHASE4	UNKNOWN	Study to Evaluate the Efficacy of Pravastatin on Survival and Recurrence of Advanced Gastroesophageal Cancer
NCT01234272	PHASE4	COMPLETED	Comparison of the Analgesic Effect Between Intrathecal Morphine and IV-fentanyl Patient Controlled Analgesia (ITM-IVPCA) and Epidural PCA (PCEA) in Patients Undergoing Gastrectomy -Randomized Allocation Study-
NCT01260194	PHASE4	TERMINATED	A Study of Herceptin (Trastuzumab) in Combination With Standard Chemotherapy in Patients With HER Positive Metastatic Gastric Cancer
NCT01271582	PHASE4	UNKNOWN	Investigation of Association Between UGT1A1 Polymorphisms and Irinotecan Toxicity in Korean Patients
NCT01401075	PHASE4	COMPLETED	RCT With Adjuvant Mistletoe Treatment in Gastric Cancer Patients
NCT01471756	PHASE4	COMPLETED	Improving Complete Endoscopic Mucosal Resection (EMR) of Colorectal Neoplasia
NCT01766765	PHASE4	UNKNOWN	Early Jejunostomy Nutrition Minimizes Time to Chemotherapy
NCT01910948	PHASE4	UNKNOWN	Perioperative Application of Omega-3 Polyunsaturated Fatty Acids in Gastric Cancer Patients
NCT01927328	PHASE4	UNKNOWN	Iron Replacement in Oesophagogastric Neoplasia
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