IGF1R

Summary

IGF1R (insulin like growth factor 1 receptor, HGNC:5465) is a protein-coding gene on chromosome 15q26.3, encoding Insulin-like growth factor 1 receptor (P08069). Receptor tyrosine kinase which mediates actions of insulin-like growth factor 1 (IGF1). In precision oncology, IGF1R NUCLEAR EXPRESSION confers sensitivity to IGF1R Monoclonal Antibody in Sarcoma (CIViC Level B); 3 further curated variant–drug associations are listed below. It is a selective cancer dependency (DepMap: 19.0% of cell lines) and haploinsufficient (ClinGen: sufficient evidence).

This receptor binds insulin-like growth factor with a high affinity. It has tyrosine kinase activity. The insulin-like growth factor I receptor plays a critical role in transformation events. Cleavage of the precursor generates alpha and beta subunits. It is highly overexpressed in most malignant tissues where it functions as an anti-apoptotic agent by enhancing cell survival. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene.

Source: NCBI Gene 3480 — RefSeq curated summary.

At a glance

• Gene–disease (curated): growth delay due to insulin-like growth factor I resistance (Definitive, GenCC)
• GWAS associations: 100
• Clinical variants (ClinVar): 1,364 total — 41 pathogenic, 38 likely-pathogenic
• Phenotypes (HPO): 59
• Druggable target: yes — 27 molecules with ChEMBL bioactivity
• Precision-oncology evidence (CIViC): 4 curated variant–drug associations
• Cancer dependency (DepMap): dependent in 19.0% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_000875

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5465
Approved symbol	IGF1R
Name	insulin like growth factor 1 receptor
Location	15q26.3
Locus type	gene with protein product
Status	Approved
Aliases	JTK13, CD221, IGFIR, MGC18216, IGFR
Ensembl gene	ENSG00000140443
Ensembl biotype	protein_coding
OMIM	147370
Entrez	3480

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 9 protein_coding_CDS_not_defined, 4 protein_coding, 3 retained_intron, 1 nonsense_mediated_decay

ENST00000557873, ENST00000557938, ENST00000558355, ENST00000558751, ENST00000558898, ENST00000558947, ENST00000559582, ENST00000559925, ENST00000560144, ENST00000560186, ENST00000560277, ENST00000560343, ENST00000560432, ENST00000560972, ENST00000561049, ENST00000649865, ENST00000650285

RefSeq mRNA: 2 — MANE Select: NM_000875 NM_000875, NM_001291858

CCDS: CCDS10378, CCDS73785

Canonical transcript exons

ENST00000650285 — 21 exons

Exon	Start	End
ENSE00001128979	98948574	98948708
ENSE00001129006	98935316	98935426
ENSE00001129013	98934824	98935053
ENSE00001129044	98923876	98924012
ENSE00001297944	98930235	98930305
ENSE00001311160	98924525	98924684
ENSE00001316091	98957061	98964530
ENSE00001318374	98929558	98929660
ENSE00001319679	98939201	98939360
ENSE00001597369	98942923	98943052
ENSE00003495266	98908685	98908899
ENSE00003528186	98899477	98899621
ENSE00003571287	98915964	98916131
ENSE00003601081	98916672	98916876
ENSE00003633139	98891325	98891637
ENSE00003665400	98911315	98911441
ENSE00003673245	98707562	98708107
ENSE00003689121	98922148	98922431
ENSE00003690630	98896757	98896905
ENSE00003690687	98913044	98913282
ENSE00003838363	98648539	98649675

Expression profiles

Bgee: expression breadth ubiquitous, 285 present calls, max score 98.47.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.1890 / max 343.0548, expressed in 1740 samples.

FANTOM5 promoters (18 alternative TSS)

Promoter ID	TPM avg	Samples expressed
148799	10.2623	1693
148805	2.9855	1094
148802	1.5236	776
148804	1.2122	555
148822	0.9830	192
148800	0.7913	504
148803	0.6075	384
148801	0.3064	157
148842	0.2423	121
207666	0.2345	111

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
caput epididymis	UBERON:0004358	98.47	gold quality
corpus epididymis	UBERON:0004359	97.88	gold quality
adrenal tissue	UBERON:0018303	97.17	gold quality
renal medulla	UBERON:0000362	97.07	gold quality
cauda epididymis	UBERON:0004360	96.70	gold quality
saphenous vein	UBERON:0007318	96.63	gold quality
mammary duct	UBERON:0001765	96.23	gold quality
sural nerve	UBERON:0015488	95.33	gold quality
bronchial epithelial cell	CL:0002328	94.97	gold quality
pigmented layer of retina	UBERON:0001782	94.97	gold quality
epithelium of mammary gland	UBERON:0003244	94.34	gold quality
stromal cell of endometrium	CL:0002255	93.96	gold quality
mucosa of paranasal sinus	UBERON:0005030	93.58	gold quality
seminal vesicle	UBERON:0000998	93.37	gold quality
nipple	UBERON:0002030	92.76	gold quality
Brodmann (1909) area 23	UBERON:0013554	92.71	gold quality
bronchus	UBERON:0002185	92.39	gold quality
epithelium of bronchus	UBERON:0002031	92.37	gold quality
nasal cavity epithelium	UBERON:0005384	92.31	gold quality
skin of hip	UBERON:0001554	91.74	gold quality
pylorus	UBERON:0001166	91.71	gold quality
urethra	UBERON:0000057	91.49	gold quality
adult organism	UBERON:0007023	91.30	gold quality
corpus callosum	UBERON:0002336	91.23	gold quality
superior vestibular nucleus	UBERON:0007227	91.18	gold quality
germinal epithelium of ovary	UBERON:0001304	91.16	gold quality
trigeminal ganglion	UBERON:0001675	91.01	gold quality
oral cavity	UBERON:0000167	90.96	gold quality
right uterine tube	UBERON:0001302	90.94	gold quality
trabecular bone tissue	UBERON:0002483	90.76	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	11.18
E-MTAB-6678	yes	8.48

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
FBN1	Activation

Upstream regulators (CollecTRI, top): AR, ARID4B, ATM, BRCA1, E2F1, EGR1, ESR1, EWSR1, FOXC1, FOXO1, GCFC2, HMGA1, HOXA9, ID4, KLF6, MYB, MYC, MYCN, NCOA3, NFKB, NKX3-1, PBX1, PGR, PITX2, RELA, SP1, STAT5A, STAT5B, TBP, TBX15, TBXT, TCF3, TP53, TP63, TP73, TXK, VHL, WT1, ZHX2, ZNF699

miRNA regulators (miRDB)

339 targeting IGF1R, 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-8485	100.00	77.57	4731
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5196-5P	100.00	67.98	2761
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-4747-5P	100.00	67.90	2681
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-186-5P	99.99	70.83	3707

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 19.0% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• X ray structure and autoregulation of the insulin-like growth factor 1 receptor kinase (PMID:11694888)
• Insulin-like growth factor receptor I mediates resistance to anti-epidermal growth factor receptor therapy in primary human glioblastoma cells through continued activation of phosphoinositide 3-kinase signaling. (PMID:11782378)
• Functional insulin-like growth factor-1/insulin-like growth factor-1 receptor-mediated circuit in human and murine thymic epithelial cells. (PMID:11867942)
• cDNA probes were used to analyze the gene expression of IGF-I receptor in luteinized granulosa cells from different-sized follicles after ovarian hyperstimulation. (PMID:12005306)
• results suggest that activation promotes neuroblastoma cell proliferation by regulating trans-membrane amino acid transport (PMID:12031683)
• results suggest a pathway of cancer cell adaptation to the tumor microenvironment in which conditions of the environment may induce expression of IGF1R, and this subsequent overexpression of the receptor may increase cell survival in such conditions (PMID:12105987)
• Autocrine production of IGF-I and IGF-II may via IGF-IR play a significant role in the growth and megakaryocytic differentiation of K562 cells. (PMID:12127559)
• Insulin-IGF1 hybrid receptors have different tissue-specific responses based on their isoforms (PMID:12138094)
• The x-ray structure of the unactivated kinase domain of insulin-like growth factor-1 receptor (IGFRK-0P) is reported here at 2.7 A resolution. (PMID:12138114)
• expression at normal levels in Nijmegen breakage syndrome cells (PMID:12147227)
• affects angiogenesis, growth, and metastasis of colon cancer (PMID:12379772)
• WT1-p53 interactions in gene regulation (PMID:12444079)
• IGF-1 receptor undergoes serine autophosphorylation and binds to 14-3-3 (PMID:12482592)
• IGF-1 receptor regulates lifespan and resistance to oxidative stress in mice (PMID:12483226)
• IGF-IR-mediated radioresistant signaling mechanism progresses through redundant downstream pathways (PMID:12493743)
• This receptor signals the inhibitor of apoptosis ASK1. (PMID:12556535)
• signaling pathways mediated by insulin-like growth factor-I receptor are required for proliferation, invasion, and VPF/VEGF expression in a pancreatic carcinoma cell line (PMID:12593846)
• IGF-IR and IGF-IIR antisense genes could significantly restrain the malignant behavior of human hepatoma cells and might be useful in investigating a potential route for hepatocellular carcinoma gene therapy. (PMID:12603530)
• First demonstration of insulin-like growth factor-I receptor on human ocular surface. (PMID:12613967)
• Shrinkage in uterine volume induced by GnRH analogs seems to be related to reduction in IGF-I-R levels. IGF-I/IGF-I-R system might affect leiomyoma growth. Action of GnRH analogs on uterine leiomyomas might be related to the effects on IGF-I-R expression. (PMID:12634644)
• Ribonucleoprotein complex assembly on the 5’-untranslated region of the IGF-IR transcript. (PMID:12644306)
• Down- and up-regulation suggests that restoration of IGF-1R would be the result of receptor recycling and de novo synthesis and highlights its importance for T lymphocyte proliferation. (PMID:12784091)
• Overexpressed and activated IGF1-R may increase the degree of transformation and motility of colon cancer cells by activating c-Src. (PMID:12820418)
• Mdm2 physically associates with IGF-1R and that Mdm2 causes IGF-1R ubiquitination in an in vitro assay. Mdm2 serves as a ligase in ubiquitination of the IGF-1R and thereby causes its degradation by the proteasome system. (PMID:12821780)
• human longevity are coregulated by an overlapping set of genes, contributing to the hypothesis that the impact of the IGF-I/insulin pathway on longevity is a property that has been evolutionarily conserved throughout the animal kingdom. (PMID:12843179)
• Ligand activation of IGF-1R protects normal human mesangial cells from glycol-oxidant-induced apoptosis program. IGF-1R-activated ERK signaling phosphorylates Ser112 of mitochondrial Bad protein, linking IGF-1R with mitochondrial survival. (PMID:12876069)
• IGF binding to the IGF1R initiates an intracellular signaling cascade in breast neoplasms that leads to changes in gene expression and cell biology [review] (PMID:12884909)
• In IGF-IR dominant negative cells decrease in constitutive and inducible phosphorylation of IGF-IR and Erk1/2. Nuclear hypoxia-inducible factor-1alpha and secreted VEGF protein levels also significantly lower. (PMID:12937141)
• IGF-1 receptor activation inhibits oxidized LDL-induced cytochrome C release and apoptosis through the phosphatidylinositol 3-kinase/Akt signaling pathway. (PMID:14551153)
• results suggest a novel function for the IGF-IR/IRS-1 pathway that involves regulation of the intracellular trafficking of Rad51 to the site of damaged DNA-a crucial step in the process of DNA repair by homologous recombination (PMID:14559999)
• results suggest a novel regulatory role of the C-terminus of IGF-IR in mediating cellular radioresistance that may be independent of survival signals transmitted through this receptor (PMID:14575710)
• role of IGF1 in cardiac myocytes in the absence of secondary effects, and downstream signaling pathways and transcriptional regulatory effects of the IGF1 receptor (PMID:14597618)
• To further understand the role of the type I insulin-like growth factor (IGF) receptor (IGF1R) in cancer metastasis we inhibited signaling via IGF1R using a C-terminal-truncated IGF1R. (PMID:14615489)
• role of IGF-1R and c-Src in human pancreatic carcinogenesis. Coexpression of both these molecules may play important role in transformation of pancreatic ductal cells. (PMID:14627343)
• The IGF1-R/Akt/Bcl-x(L) pathway may contribute to a more aggressive malignant phenotype, in a subset of colorectal cancers. (PMID:14633695)
• These findings suggest that 14-3-3 proteins interact with the IGFIR in vivo and that this interaction may play a role in a transformation pathway signaled by the IGFIR. (PMID:14651979)
• Coexpression of insulin receptor-related receptor and insulin-like growth factor 1 receptor correlates with enhanced apoptosis and dedifferentiation in human neuroblastomas. (PMID:14654552)
• IGF I receptor is involved in apoptosis protection in human preadipocytes and adipocytes. (PMID:14691011)
• IGF-IR mediated attenuation of antineoplastic agent-induced growth inhibition is dependent on IGF-I-induced PI3K signaling rather than IGF-I-induced MAPK signaling (PMID:14697248)
• Activation of IGF-I receptor can selectively enhance the previously reported IGF-I receptor pro-apoptotic signaling pathways. (PMID:14710354)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	igf1ra	ENSDARG00000027423
danio_rerio	igf1rb	ENSDARG00000034434
mus_musculus	Igf1r	ENSMUSG00000005533
rattus_norvegicus	Igf1r	ENSRNOG00000014187

Paralogs (53): INSRR (ENSG00000027644), MUSK (ENSG00000030304), FLT4 (ENSG00000037280), EPHA3 (ENSG00000044524), ROS1 (ENSG00000047936), LTK (ENSG00000062524), ERBB3 (ENSG00000065361), TIE1 (ENSG00000066056), FGFR2 (ENSG00000066468), FGFR3 (ENSG00000068078), EPHA8 (ENSG00000070886), FGFR1 (ENSG00000077782), EPHA6 (ENSG00000080224), TYRO3 (ENSG00000092445), FLT1 (ENSG00000102755), MET (ENSG00000105976), EPHB6 (ENSG00000106123), PDGFRB (ENSG00000113721), EPHA4 (ENSG00000116106), TEK (ENSG00000120156), FLT3 (ENSG00000122025), KDR (ENSG00000128052), EPHB2 (ENSG00000133216), PDGFRA (ENSG00000134853), EPHA7 (ENSG00000135333), NTRK3 (ENSG00000140538), ERBB2 (ENSG00000141736), EPHA2 (ENSG00000142627), EPHA5 (ENSG00000145242), EGFR (ENSG00000146648), EPHA1 (ENSG00000146904), NTRK2 (ENSG00000148053), MERTK (ENSG00000153208), EPHB1 (ENSG00000154928), KIT (ENSG00000157404), FGFR4 (ENSG00000160867), DDR2 (ENSG00000162733), RYK (ENSG00000163785), MST1R (ENSG00000164078), LMTK2 (ENSG00000164715)

Protein

Protein identifiers

Insulin-like growth factor 1 receptor — P08069 (reviewed: P08069)

Alternative names: Insulin-like growth factor I receptor

All UniProt accessions (5): P08069, C9J5X1, H0YMJ5, H0YNR0, H3BSZ8

UniProt curated annotations — full annotation on UniProt →

Function. Receptor tyrosine kinase which mediates actions of insulin-like growth factor 1 (IGF1). Binds IGF1 with high affinity and IGF2 and insulin (INS) with a lower affinity. The activated IGF1R is involved in cell growth and survival control. IGF1R is crucial for tumor transformation and survival of malignant cell. Ligand binding activates the receptor kinase, leading to receptor autophosphorylation, and tyrosines phosphorylation of multiple substrates, that function as signaling adapter proteins including, the insulin-receptor substrates (IRS1/2), Shc and 14-3-3 proteins. Phosphorylation of IRSs proteins lead to the activation of two main signaling pathways: the PI3K-AKT/PKB pathway and the Ras-MAPK pathway. The result of activating the MAPK pathway is increased cellular proliferation, whereas activating the PI3K pathway inhibits apoptosis and stimulates protein synthesis. Phosphorylated IRS1 can activate the 85 kDa regulatory subunit of PI3K (PIK3R1), leading to activation of several downstream substrates, including protein AKT/PKB. AKT phosphorylation, in turn, enhances protein synthesis through mTOR activation and triggers the antiapoptotic effects of IGFIR through phosphorylation and inactivation of BAD. In parallel to PI3K-driven signaling, recruitment of Grb2/SOS by phosphorylated IRS1 or Shc leads to recruitment of Ras and activation of the ras-MAPK pathway. In addition to these two main signaling pathways IGF1R signals also through the Janus kinase/signal transducer and activator of transcription pathway (JAK/STAT). Phosphorylation of JAK proteins can lead to phosphorylation/activation of signal transducers and activators of transcription (STAT) proteins. In particular activation of STAT3, may be essential for the transforming activity of IGF1R. The JAK/STAT pathway activates gene transcription and may be responsible for the transforming activity. JNK kinases can also be activated by the IGF1R. IGF1 exerts inhibiting activities on JNK activation via phosphorylation and inhibition of MAP3K5/ASK1, which is able to directly associate with the IGF1R. When present in a hybrid receptor with INSR, binds IGF1. PubMed:12138094 shows that hybrid receptors composed of IGF1R and INSR isoform Long are activated with a high affinity by IGF1, with low affinity by IGF2 and not significantly activated by insulin, and that hybrid receptors composed of IGF1R and INSR isoform Short are activated by IGF1, IGF2 and insulin. In contrast, PubMed:16831875 shows that hybrid receptors composed of IGF1R and INSR isoform Long and hybrid receptors composed of IGF1R and INSR isoform Short have similar binding characteristics, both bind IGF1 and have a low affinity for insulin.

Subunit / interactions. Tetramer of 2 alpha and 2 beta chains linked by disulfide bonds. The alpha chains contribute to the formation of the ligand-binding domain, while the beta chain carries the kinase domain. Interacts with PIK3R1 and with the PTB/PID domains of IRS1 and SHC1 in vitro when autophosphorylated on tyrosine residues. Forms a hybrid receptor with INSR, the hybrid is a tetramer consisting of 1 alpha chain and 1 beta chain of INSR and 1 alpha chain and 1 beta chain of IGF1R. Interacts with ARRB1 and ARRB2. Interacts with GRB10. Interacts with RACK1. Interacts with SOCS1, SOCS2 and SOCS3. Interacts with 14-3-3 proteins. Interacts with NMD2. Interacts with MAP3K5. Interacts with STAT3. Found in a ternary complex with IGF1 and ITGAV:ITGB3 or ITGA6:ITGB4. Interacts (nascent precursor form) with ZFAND2B. (Microbial infection) Interacts with human respiratory syncytial virus (HRSV) fusion glycoprotein F1/F2 heterodimer.

Subcellular location. Cell membrane.

Tissue specificity. Found as a hybrid receptor with INSR in muscle, heart, kidney, adipose tissue, skeletal muscle, hepatoma, fibroblasts, spleen and placenta (at protein level). Expressed in a variety of tissues. Overexpressed in tumors, including melanomas, cancers of the colon, pancreas prostate and kidney.

Post-translational modifications. Autophosphorylated on tyrosine residues in response to ligand binding. Autophosphorylation occurs in trans, i.e. one subunit of the dimeric receptor phosphorylates tyrosine residues on the other subunit. Autophosphorylation occurs in a sequential manner; Tyr-1165 is predominantly phosphorylated first, followed by phosphorylation of Tyr-1161 and Tyr-1166. While every single phosphorylation increases kinase activity, all three tyrosine residues in the kinase activation loop (Tyr-1165, Tyr-1161 and Tyr-1166) have to be phosphorylated for optimal activity. Can be autophosphorylated at additional tyrosine residues (in vitro). Autophosphorylated is followed by phosphorylation of juxtamembrane tyrosines and C-terminal serines. May also be phosphorylated at Tyr-1161 and Tyr-1166 by mTORC2. Phosphorylation of Tyr-980 is required for IRS1- and SHC1-binding. Phosphorylation of Ser-1278 by GSK-3beta restrains kinase activity and promotes cell surface expression, it requires a priming phosphorylation at Ser-1282. Dephosphorylated by PTPN1. Polyubiquitinated at Lys-1168 and Lys-1171 through both ‘Lys-48’ and ‘Lys-29’ linkages, promoting receptor endocytosis and subsequent degradation by the proteasome. Ubiquitination is facilitated by pre-existing phosphorylation. Sumoylated with SUMO1. Controlled by regulated intramembrane proteolysis (RIP). Undergoes metalloprotease-dependent constitutive ectodomain shedding to produce a membrane-anchored 52 kDa C-Terminal fragment which is further processed by presenilin gamma-secretase to yield an intracellular 50 kDa fragment.

Disease relevance. Insulin-like growth factor 1 resistance (IGF1RES) [MIM:270450] A disorder characterized by intrauterine growth retardation, poor postnatal growth and increased plasma IGF1 levels. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Activated by autophosphorylation at Tyr-1165, Tyr-1161 and Tyr-1166 on the kinase activation loop; phosphorylation at all three tyrosine residues is required for optimal kinase activity. Inhibited by MSC1609119A-1, BMS-754807, PQIP, benzimidazole pyridinone, isoquinolinedione, bis-azaindole, 3-cyanoquinoline, 2,4-bis-arylamino-1,3-pyrimidine, pyrrolopyrimidine, pyrrole-5-carboxaldehyde, picropodophyllin (PPP), tyrphostin derivatives. While most inhibitors bind to the ATP binding pocket, MSC1609119A-1 functions as allosteric inhibitor and binds close to the DFG motif and the activation loop.

Similarity. Belongs to the protein kinase superfamily. Tyr protein kinase family. Insulin receptor subfamily.

RefSeq proteins (2): NP_000866, NP_001278787 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000494	Rcpt_L-dom	Domain
IPR000719	Prot_kinase_dom	Domain
IPR001245	Ser-Thr/Tyr_kinase_cat_dom	Domain
IPR002011	Tyr_kinase_rcpt_2_CS	Conserved_site
IPR003961	FN3_dom	Domain
IPR006211	Furin-like_Cys-rich_dom	Domain
IPR006212	Furin_repeat	Repeat
IPR008266	Tyr_kinase_AS	Active_site
IPR009030	Growth_fac_rcpt_cys_sf	Homologous_superfamily
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR013783	Ig-like_fold	Homologous_superfamily
IPR016246	Tyr_kinase_insulin-like_rcpt	Family
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR020635	Tyr_kinase_cat_dom	Domain
IPR036116	FN3_sf	Homologous_superfamily
IPR036941	Rcpt_L-dom_sf	Homologous_superfamily
IPR050122	RTK	Family

Pfam: PF00757, PF01030, PF07714

Enzyme classification (BRENDA):

• EC 2.7.10.1 — receptor protein-tyrosine kinase (BRENDA: 44 organisms, 214 substrates, 574 inhibitors, 11 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

4 substrates with measured Km, best-characterized 4. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.0011–0.129	4
AC-DYFE-6-CHLORO-W-NHME	0.0051	1
AC-DYFGW-NHME	0.07	1
YFEW	0.232	1

Catalyzed reactions (Rhea), 1 shown:

• L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+) (RHEA:10596)

UniProt features (207 total): strand 75, helix 35, sequence variant 18, glycosylation site 16, turn 15, disulfide bond 15, modified residue 6, domain 5, mutagenesis site 5, compositionally biased region 3, chain 2, binding site 2, topological domain 2, cross-link 2, signal peptide 1, region of interest 1, short sequence motif 1, active site 1, transmembrane region 1, sequence conflict 1

Structure

Experimental structures (PDB)

46 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
1P4O	X-RAY DIFFRACTION	1.5
8PYN	X-RAY DIFFRACTION	1.71
3LW0	X-RAY DIFFRACTION	1.79
5FXS	X-RAY DIFFRACTION	1.9
2OJ9	X-RAY DIFFRACTION	2
3I81	X-RAY DIFFRACTION	2.08
1JQH	X-RAY DIFFRACTION	2.1
1K3A	X-RAY DIFFRACTION	2.1
3O23	X-RAY DIFFRACTION	2.1
4D2R	X-RAY DIFFRACTION	2.1
3NW7	X-RAY DIFFRACTION	2.11
3NW5	X-RAY DIFFRACTION	2.14
3NW6	X-RAY DIFFRACTION	2.2
5HZN	X-RAY DIFFRACTION	2.2
8PYK	X-RAY DIFFRACTION	2.23
3D94	X-RAY DIFFRACTION	2.3
5FXQ	X-RAY DIFFRACTION	2.3
5FXR	X-RAY DIFFRACTION	2.4
2ZM3	X-RAY DIFFRACTION	2.5
1IGR	X-RAY DIFFRACTION	2.6
8PYM	X-RAY DIFFRACTION	2.65
1M7N	X-RAY DIFFRACTION	2.7
8PYJ	X-RAY DIFFRACTION	2.7
3F5P	X-RAY DIFFRACTION	2.9
3QQU	X-RAY DIFFRACTION	2.9
8PYL	X-RAY DIFFRACTION	2.93
3LVP	X-RAY DIFFRACTION	3
4XSS	X-RAY DIFFRACTION	3
5U8R	X-RAY DIFFRACTION	3
8TAN	ELECTRON MICROSCOPY	3.05

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P08069-F1	78.54	0.45

Antibody-complex structures (SAbDab): 2 — 5U8Q, 5U8R

Functional residue map

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

Catalytic / active sites (1): 1135 (proton acceptor)

Ligand- & substrate-binding residues (2): 1005–1013; 1033

Post-translational modifications (8): 980, 1161, 1165, 1166, 1278, 1282, 1168, 1171

Disulfide bonds (15): 33–52, 150–178, 182–205, 192–211, 215–224, 219–230, 231–239, 235–248, 251–260, 264–276, 282–303, 307–321, 324–328, 332–353, 455–488

Glycosylation sites (16): 51, 102, 135, 244, 314, 417, 438, 534, 607, 622, 640, 747, 756, 764, 900, 913

Mutagenesis-validated functional residues (5):

Position	Phenotype
980	reduces tyrosine phosphorylation. abolishes interaction with irs1 and shc1. does not abolish interaction with pik3r1, no
1033	kinase inactive. abolishes tyrosine phosphorylation and abolishes interaction with irs1, shc1 and pik3r1.
1280	no effect on grb10-binding.
1281	no effect on grb10-binding.
1346	loss of grb10-binding.

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-2404192	Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R)
R-HSA-2428928	IRS-related events triggered by IGF1R
R-HSA-2428933	SHC-related events triggered by IGF1R
R-HSA-9009391	Extra-nuclear estrogen signaling
R-HSA-9820960	Respiratory syncytial virus (RSV) attachment and entry

MSigDB gene sets: 698 (showing top): PID_SHP2_PATHWAY, GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_UP, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, BERENJENO_ROCK_SIGNALING_NOT_VIA_RHOA_DN, BIOCARTA_TEL_PATHWAY, DACOSTA_UV_RESPONSE_VIA_ERCC3_XPCS_DN, FISCHER_G1_S_CELL_CYCLE, PEREZ_TP63_TARGETS, GCANCTGNY_MYOD_Q6, GOZGIT_ESR1_TARGETS_DN, GOBP_CELLULAR_RESPONSE_TO_CARBOHYDRATE_STIMULUS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, LINDGREN_BLADDER_CANCER_CLUSTER_3_DN, GOBP_CELLULAR_COMPONENT_MAINTENANCE

GO Biological Process (24): immune response (GO:0006955), signal transduction (GO:0007165), positive regulation of cell population proliferation (GO:0008284), insulin receptor signaling pathway (GO:0008286), positive regulation of cell migration (GO:0030335), peptidyl-tyrosine autophosphorylation (GO:0038083), negative regulation of apoptotic process (GO:0043066), positive regulation of protein-containing complex disassembly (GO:0043243), negative regulation of MAPK cascade (GO:0043409), positive regulation of MAPK cascade (GO:0043410), phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0043491), transcytosis (GO:0045056), regulation of JNK cascade (GO:0046328), protein autophosphorylation (GO:0046777), insulin-like growth factor receptor signaling pathway (GO:0048009), positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897), cellular response to glucose stimulus (GO:0071333), dendritic spine maintenance (GO:0097062), amyloid-beta clearance (GO:0097242), positive regulation of cold-induced thermogenesis (GO:0120162), cellular response to amyloid-beta (GO:1904646), protein phosphorylation (GO:0006468), cell surface receptor protein tyrosine kinase signaling pathway (GO:0007169), cellular response to oxygen-containing compound (GO:1901701)

GO Molecular Function (18): protein tyrosine kinase activity (GO:0004713), insulin receptor activity (GO:0005009), insulin-like growth factor receptor activity (GO:0005010), insulin receptor binding (GO:0005158), insulin-like growth factor binding (GO:0005520), ATP binding (GO:0005524), insulin-like growth factor I binding (GO:0031994), identical protein binding (GO:0042802), phosphatidylinositol 3-kinase binding (GO:0043548), insulin binding (GO:0043559), insulin receptor substrate binding (GO:0043560), protein transporter activity (GO:0140318), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), transmembrane receptor protein tyrosine kinase activity (GO:0004714), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (9): nucleolus (GO:0005730), plasma membrane (GO:0005886), insulin receptor complex (GO:0005899), cilium (GO:0005929), membrane (GO:0016020), axon (GO:0030424), alphav-beta3 integrin-IGF-1-IGF1R complex (GO:0035867), signaling receptor complex (GO:0043235), protein kinase complex (GO:1902911)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
IGF1R signaling cascade	2
Signaling by Receptor Tyrosine Kinases	1
ESR-mediated signaling	1
Respiratory Syncytial Virus Infection Pathway	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein binding	4
regulation of MAPK cascade	3
cell surface receptor protein tyrosine kinase signaling pathway	2
MAPK cascade	2
positive regulation of intracellular signal transduction	2
multicellular organismal process	2
transmembrane receptor protein tyrosine kinase activity	2
insulin-like growth factor binding	2
immune system process	1
response to stimulus	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
cellular response to insulin stimulus	1
cell migration	1
regulation of cell migration	1
positive regulation of cell motility	1
peptidyl-tyrosine phosphorylation	1
protein autophosphorylation	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
protein-containing complex disassembly	1
regulation of protein-containing complex disassembly	1
positive regulation of cellular component organization	1
negative regulation of intracellular signal transduction	1
intracellular signaling cassette	1
vesicle-mediated transport	1
JNK cascade	1
protein phosphorylation	1
phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
intracellular glucose homeostasis	1
response to glucose	1
cellular response to hexose stimulus	1

Protein interactions and networks

STRING

5824 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IGF1R	IGF1	P01343	999
IGF1R	INS	P01308	999
IGF1R	IGF2	P01344	999
IGF1R	IRS1	P35568	998
IGF1R	ESR1	P03372	994
IGF1R	SHC1	P29353	993
IGF1R	GRB10	Q13322	981
IGF1R	ERBB2	P04626	980
IGF1R	EGF	P01133	979
IGF1R	APPL1	Q9UKG1	976
IGF1R	IRS2	Q9Y4H2	974
IGF1R	EGFR	P00533	973
IGF1R	CAV1	Q03135	963
IGF1R	SRC	P12931	959
IGF1R	TSHR	P16473	950

IntAct

362 interactions, top by confidence:

A	B	Type	Score
YWHAE	RAF1	psi-mi:“MI:0914”(association)	0.920
IGF1R	YWHAB	psi-mi:“MI:0915”(physical association)	0.830
IGF1R	IGF1R	psi-mi:“MI:0914”(association)	0.800
IGF1R	IGF1R	psi-mi:“MI:0915”(physical association)	0.800
IGF1R	IGF1R	psi-mi:“MI:0407”(direct interaction)	0.800
IGF1R	IGF1R	psi-mi:“MI:0195”(covalent binding)	0.800
PIK3R1	IGF1R	psi-mi:“MI:2364”(proximity)	0.800
IGF1R	IGF1	psi-mi:“MI:0407”(direct interaction)	0.780
C1QTNF9	C1QTNF9B	psi-mi:“MI:0914”(association)	0.780
PTPN11	IGF1R	psi-mi:“MI:0915”(physical association)	0.770
KCNIP3	IGF1R	psi-mi:“MI:0915”(physical association)	0.720
IGF1R	KCNIP3	psi-mi:“MI:0915”(physical association)	0.720
INSR	IGF1R	psi-mi:“MI:0915”(physical association)	0.650
IGF1R	INSR	psi-mi:“MI:0914”(association)	0.650
INSRR	INSR	psi-mi:“MI:0914”(association)	0.650
SCGB1D1	MANBA	psi-mi:“MI:0914”(association)	0.640
YWHAE	IGF1R	psi-mi:“MI:0915”(physical association)	0.630
YWHAE	IGF1R	psi-mi:“MI:0914”(association)	0.630
PIK3R2	IGF1R	psi-mi:“MI:0915”(physical association)	0.590
IGF1R	PIK3R2	psi-mi:“MI:2364”(proximity)	0.590
INSR	PIK3R2	psi-mi:“MI:2364”(proximity)	0.570
ITGB1	IGF1R	psi-mi:“MI:0915”(physical association)	0.560
Irs1	IGF1R	psi-mi:“MI:0915”(physical association)	0.550
SPOP	IGF1R	psi-mi:“MI:0915”(physical association)	0.550
IGF1R	SPOP	psi-mi:“MI:2364”(proximity)	0.550

BioGRID (637): KCNIP3 (Two-hybrid), IGF1R (Affinity Capture-MS), FDPS (Co-fractionation), BAP1 (Two-hybrid), CYP17A1 (Two-hybrid), HOXC6 (Two-hybrid), IL13RA2 (Two-hybrid), KLK5 (Two-hybrid), LYPD3 (Two-hybrid), MTA3 (Two-hybrid), NAT2 (Two-hybrid), THRSP (Two-hybrid), TRIM25 (Two-hybrid), VPS45 (Two-hybrid), IGF1R (Affinity Capture-MS)

ESM2 similar proteins: A2RSQ1, A3KPQ7, M9NDE3, O73798, O75339, P08069, P12890, P15127, P15208, P16098, P24062, P34501, P51559, P82993, Q00PJ8, Q07DV8, Q07DY1, Q07E01, Q07E24, Q07E48, Q09YH7, Q09YI9, Q09YK0, Q09YL1, Q0INM3, Q0IZZ8, Q108U6, Q2IBC0, Q2IBG7, Q2QL89, Q2QLC0, Q2QLG5, Q2QLH6, Q54YG8, Q5FWI3, Q60751, Q60HF6, Q66K08, Q75ZY9, Q765H6

Diamond homologs: A0A0K3AV08, A7J1T0, A7J1T2, A7MBB4, A8X775, D3ZG83, G5EE56, H2KZW3, O01700, O19064, O22558, O43283, O54967, O60674, P00529, P00533, P00534, P00535, P03949, P04412, P06239, P06240, P08069, P08922, P08941, P09760, P09769, P11273, P11362, P13388, P14234, P14616, P14617, P16092, P16591, P18461, P21802, P21803, P21804, P22607

SIGNOR signaling

77 interactions.

A	Effect	B	Mechanism
IGF1R	up-regulates	SIRPA
PTPN1	“down-regulates activity”	IGF1R	dephosphorylation
IGF1R	up-regulates	IRS1	phosphorylation
IGF1R	up-regulates	PDPK1	phosphorylation
GRB10	down-regulates	IGF1R	binding
IGF1	“up-regulates activity”	IGF1R	binding
IGF1R	up-regulates	PIK3R1	binding
IGF1	up-regulates	IGF1R	binding
2-[(3-bromo-5-tert-butyl-4-hydroxyphenyl)methylidene]propanedinitrile	down-regulates	IGF1R	“chemical inhibition”
4-[[(2S)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]-3-[4-methyl-6-(4-morpholinyl)-1,3-dihydrobenzimidazol-2-ylidene]-2-pyridinone	down-regulates	IGF1R	“chemical inhibition”
BMS-554417	down-regulates	IGF1R	“chemical inhibition”
BMS-754807	down-regulates	IGF1R	“chemical inhibition”
2-[[2-[[1-[2-(dimethylamino)-1-oxoethyl]-5-methoxy-2,3-dihydroindol-6-yl]amino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino]-6-fluoro-N-methylbenzamide	down-regulates	IGF1R	“chemical inhibition”
N-(2,6-difluorophenyl)-5-[3-[2-[5-ethyl-2-methoxy-4-[4-(4-methylsulfonyl-1-piperazinyl)-1-piperidinyl]anilino]-4-pyrimidinyl]-2-imidazo[1,2-a]pyridinyl]-2-methoxybenzamide	down-regulates	IGF1R	“chemical inhibition”
3-[8-amino-1-(2-phenyl-7-quinolinyl)-3-imidazo[1,5-a]pyrazinyl]-1-methyl-1-cyclobutanol	down-regulates	IGF1R	“chemical inhibition”
NVP-ADW742	down-regulates	IGF1R	“chemical inhibition”
NVP-AEW541	down-regulates	IGF1R	“chemical inhibition”
INS	up-regulates	IGF1R	binding
PAX7-FOXO1	“up-regulates quantity by expression”	IGF1R	“transcriptional regulation”
IGF2	“up-regulates activity”	IGF1R	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 174 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
Activation of BAD and translocation to mitochondria	5	33.7×	5e-05
Signaling by ALK	6	30.3×	2e-05
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	5	29.7×	5e-05
Tie2 Signaling	5	26.6×	8e-05
Interleukin-37 signaling	5	23.0×	1e-04
Activation of BH3-only proteins	5	22.0×	1e-04
Regulation of signaling by CBL	5	22.0×	1e-04
Downstream signal transduction	6	20.2×	5e-05

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of glycogen biosynthetic process	5	32.8×	1e-04
peptidyl-tyrosine dephosphorylation	5	29.4×	2e-04
insulin-like growth factor receptor signaling pathway	7	23.0×	1e-05
positive regulation of D-glucose import across plasma membrane	6	18.1×	2e-04
insulin receptor signaling pathway	12	17.6×	4e-09
phosphatidylinositol 3-kinase/protein kinase B signal transduction	8	11.2×	2e-04
protein dephosphorylation	7	10.3×	1e-03
epidermal growth factor receptor signaling pathway	6	9.8×	3e-03

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

1364 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	41
Likely pathogenic	38
Uncertain significance	744
Likely benign	341
Benign	73

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1188841	NM_000875.5(IGF1R):c.2321_2322del (p.Glu774fs)	Pathogenic
153592	GRCh38/hg38 15q26.3(chr15:98892707-99182753)x1	Pathogenic
1723826	NM_000875.5(IGF1R):c.3190C>T (p.Arg1064Ter)	Pathogenic
2305842	NM_000875.5(IGF1R):c.1030del (p.Val344fs)	Pathogenic
2443553	NM_000875.5(IGF1R):c.641-2A>G	Pathogenic
2570917	GRCh37/hg19 15q26.3(chr15:99434554-99550600)x1	Pathogenic
2836667	NM_000875.5(IGF1R):c.148G>T (p.Glu50Ter)	Pathogenic
2851464	NM_000875.5(IGF1R):c.1722G>A (p.Trp574Ter)	Pathogenic
2875102	NM_000875.5(IGF1R):c.45del (p.Leu16fs)	Pathogenic
3063393	GRCh37/hg19 15q26.3(chr15:99477386-100023041)x3	Pathogenic
3065985	NM_000875.5(IGF1R):c.822G>A (p.Trp274Ter)	Pathogenic
3237340	NM_000875.5(IGF1R):c.2477_2480dup (p.Glu829fs)	Pathogenic
3243861	NC_000015.9:g.(?99192811)(99505828_?)del	Pathogenic
3366330	NM_000875.5(IGF1R):c.3464G>C (p.Gly1155Ala)	Pathogenic
3366906	NM_000875.5(IGF1R):c.2132_2143del (p.Ala711_Glu714del)	Pathogenic
3371475	NM_000875.5(IGF1R):c.921C>A (p.Cys307Ter)	Pathogenic
3376747	NM_000875.5(IGF1R):c.2607C>G (p.Tyr869Ter)	Pathogenic
3630030	NM_000875.5(IGF1R):c.2331_2332del (p.Phe777_Phe778insTer)	Pathogenic
3657732	NM_000875.5(IGF1R):c.1893G>A (p.Trp631Ter)	Pathogenic
3895661	NM_000875.5(IGF1R):c.3534dup (p.Met1179fs)	Pathogenic
392286	NM_000875.5(IGF1R):c.1590-1G>C	Pathogenic
4076020	GRCh37/hg19 15q26.3(chr15:99435798-99739132)x1	Pathogenic
4274046	NM_000875.5(IGF1R):c.3211C>T (p.Gln1071Ter)	Pathogenic
4278639	NM_000875.5(IGF1R):c.3391T>G (p.Phe1131Val)	Pathogenic
4281628	NM_000875.5(IGF1R):c.1285C>T (p.Gln429Ter)	Pathogenic
4281656	NM_000875.5(IGF1R):c.1102+2T>C	Pathogenic
431965	NM_000875.5(IGF1R):c.3348_3366dup (p.Met1123fs)	Pathogenic
451669	NM_000875.5(IGF1R):c.2578G>T (p.Gly860Ter)	Pathogenic
4532780	NM_000875.5(IGF1R):c.2097C>A (p.Cys699Ter)	Pathogenic
4536746	NM_000875.5(IGF1R):c.1338_1353del (p.Met446fs)	Pathogenic

SpliceAI

6637 predictions. Top by Δscore:

Variant	Effect	Δscore
15:98707558:TCA:T	acceptor_loss	1.0000
15:98707558:TCAG:T	acceptor_gain	1.0000
15:98707560:A:AG	acceptor_gain	1.0000
15:98707560:AGTCT:A	acceptor_gain	1.0000
15:98707561:G:GT	acceptor_gain	1.0000
15:98707561:GT:G	acceptor_gain	1.0000
15:98707561:GTC:G	acceptor_gain	1.0000
15:98707561:GTCT:G	acceptor_gain	1.0000
15:98707561:GTCTG:G	acceptor_gain	1.0000
15:98708103:GAAAA:G	donor_gain	1.0000
15:98708108:G:GG	donor_gain	1.0000
15:98769420:A:G	acceptor_gain	1.0000
15:98891320:CACA:C	acceptor_loss	1.0000
15:98891322:CA:C	acceptor_loss	1.0000
15:98891323:A:AG	acceptor_gain	1.0000
15:98891323:AG:A	acceptor_loss	1.0000
15:98891323:AGT:A	acceptor_gain	1.0000
15:98891324:G:GA	acceptor_gain	1.0000
15:98891324:GT:G	acceptor_gain	1.0000
15:98891324:GTG:G	acceptor_gain	1.0000
15:98891324:GTGT:G	acceptor_gain	1.0000
15:98891633:CAGAG:C	donor_loss	1.0000
15:98891634:AGAG:A	donor_loss	1.0000
15:98891635:GAG:G	donor_gain	1.0000
15:98891635:GAGGT:G	donor_loss	1.0000
15:98891637:GGT:G	donor_loss	1.0000
15:98891638:G:A	donor_loss	1.0000
15:98891639:T:A	donor_loss	1.0000
15:98896755:A:AG	acceptor_gain	1.0000
15:98896755:AGCAT:A	acceptor_gain	1.0000

AlphaMissense

9050 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:98707621:T:A	C52S	1.000
15:98707621:T:C	C52R	1.000
15:98707622:G:C	C52S	1.000
15:98707636:G:T	G57C	1.000
15:98707643:T:C	L59P	1.000
15:98707700:T:A	L78H	1.000
15:98707700:T:C	L78P	1.000
15:98707724:T:C	L86P	1.000
15:98707775:T:A	L103H	1.000
15:98707775:T:C	L103P	1.000
15:98707789:G:T	G108C	1.000
15:98707817:T:C	L117P	1.000
15:98707865:T:C	L133P	1.000
15:98707905:T:A	N146K	1.000
15:98707905:T:G	N146K	1.000
15:98707913:T:C	L149P	1.000
15:98707915:T:A	C150S	1.000
15:98707916:G:A	C150Y	1.000
15:98707916:G:C	C150S	1.000
15:98707917:T:G	C150W	1.000
15:98707936:T:A	W157R	1.000
15:98707936:T:C	W157R	1.000
15:98707938:G:C	W157C	1.000
15:98707938:G:T	W157C	1.000
15:98708080:T:A	C205S	1.000
15:98708080:T:C	C205R	1.000
15:98708081:G:C	C205S	1.000
15:98708082:C:G	C205W	1.000
15:98708083:T:A	W206R	1.000
15:98708083:T:C	W206R	1.000

dbSNP variants (sampled 300 via entrez): RS1000003525 (15:98952088 T>C), RS1000010021 (15:98958740 T>C), RS1000017954 (15:98647497 C>A,G), RS1000022035 (15:98850623 A>C,G), RS1000024788 (15:98855344 A>G), RS1000052521 (15:98718458 G>A,T), RS1000069935 (15:98945072 C>T), RS1000070789 (15:98755707 A>C), RS1000079354 (15:98719333 C>T), RS1000092452 (15:98894434 G>A,C,T), RS1000114192 (15:98836926 G>A), RS1000135287 (15:98792904 A>C,G), RS1000160502 (15:98668382 G>A), RS1000170485 (15:98739191 G>A,C,T), RS1000179836 (15:98904360 G>A)

Disease associations

OMIM: gene MIM:147370 | disease phenotypes: MIM:270450, MIM:148300, MIM:123100

GenCC curated gene-disease

Disease	Classification	Inheritance
growth delay due to insulin-like growth factor I resistance	Definitive	Autosomal dominant

Mondo (7): growth delay due to insulin-like growth factor I resistance (MONDO:0010038), neurodevelopmental disorder (MONDO:0700092), microcephaly (MONDO:0001149), keratoconus (MONDO:0015486), NK-cell enteropathy (MONDO:0016996), craniosynostosis (MONDO:0015469), intellectual disability (MONDO:0001071)

Orphanet (6): Growth delay due to insulin-like growth factor I resistance (Orphanet:73273), NK-cell enteropathy (Orphanet:263665), Craniosynostosis (Orphanet:1531), OBSOLETE: Keratoconus (Orphanet:156071), NON RARE IN EUROPE: Isolated keratoconus (Orphanet:2335), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

59 total (30 of 59 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000160	Narrow mouth
HP:0000218	High palate
HP:0000219	Thin upper lip vermilion
HP:0000232	Everted lower lip vermilion
HP:0000233	Thin vermilion border
HP:0000252	Microcephaly
HP:0000278	Retrognathia
HP:0000319	Smooth philtrum
HP:0000325	Triangular face
HP:0000343	Long philtrum
HP:0000347	Micrognathia
HP:0000369	Low-set ears
HP:0000431	Wide nasal bridge
HP:0000455	Broad nasal tip
HP:0000465	Webbed neck
HP:0000486	Strabismus
HP:0000490	Deeply set eye
HP:0000558	Rieger anomaly
HP:0000574	Thick eyebrow
HP:0000582	Upslanted palpebral fissure
HP:0000664	Synophrys
HP:0000713	Agitation
HP:0000739	Anxiety
HP:0000750	Delayed speech and language development
HP:0000767	Pectus excavatum
HP:0000819	Diabetes mellitus
HP:0001249	Intellectual disability
HP:0001263	Global developmental delay

GWAS associations

100 associations (top):

Study	Trait	p-value
GCST000817_118	Height	3.000000e-21
GCST001417_4	Arthritis (juvenile idiopathic)	7.000000e-07
GCST001791_41	Urate levels	5.000000e-15
GCST002586_3	Fasting plasma glucose	3.000000e-08
GCST002702_74	Height	6.000000e-23
GCST003819_3	Endometriosis	2.000000e-09
GCST004603_237	Platelet count	2.000000e-12
GCST004607_59	Plateletcrit	1.000000e-11
GCST005146_26	Birth weight	1.000000e-09
GCST005790_37	Rosacea symptom severity	6.000000e-06
GCST005905_10	Global electrical heterogeneity phenotypes	1.000000e-12
GCST005983_4	Serum uric acid levels	2.000000e-13
GCST005984_59	Glomerular filtration rate	2.000000e-10
GCST005985_14	Creatinine levels	3.000000e-13
GCST005986_21	Blood urea nitrogen levels	4.000000e-10
GCST006061_225	Atrial fibrillation	1.000000e-10
GCST006061_226	Atrial fibrillation	2.000000e-10
GCST006414_29	Atrial fibrillation	1.000000e-10
GCST007103_23	QRS duration	3.000000e-09
GCST007104_23	QRS duration	8.000000e-10
GCST007323_97	Risk-taking tendency (4-domain principal component model)	2.000000e-09
GCST007327_140	Smoking status (ever vs never smokers)	4.000000e-09
GCST007344_4	Estimated glomerular filtration rate	2.000000e-09
GCST007725_11	Serum uric acid levels	4.000000e-16
GCST007733_45	Serum uric acid levels	2.000000e-15
GCST007733_47	Serum uric acid levels	4.000000e-14
GCST007876_31	Estimated glomerular filtration rate	2.000000e-12
GCST007916_13	Hyperuricemia	2.000000e-16
GCST007917_16	Estimated glomerular filtration rate	2.000000e-16
GCST007918_26	Serum uric acid levels	2.000000e-16

EFO canonical traits (23, from GWAS)

EFO ID	Trait name
EFO:0004531	urate measurement
EFO:0004309	platelet count
EFO:0007985	platelet crit
EFO:0004344	birth weight
EFO:0009180	rosacea severity measurement
EFO:0004327	electrocardiography
EFO:0004761	uric acid measurement
EFO:0008579	risk-taking behaviour
EFO:0004318	smoking behavior
EFO:0009104	hyperuricemia
EFO:0005939	parental genotype effect measurement
EFO:0006939	cup-to-disc ratio measurement
EFO:0004530	triglyceride measurement
EFO:0004644	TPE interval measurement
EFO:0009289	left ventricular mass
EFO:0010556	Left ventricular mass to end-diastolic volume ratio
EFO:0008205	left ventricular structural measurement
EFO:0007789	BMI-adjusted waist circumference
EFO:0008039	BMI-adjusted hip circumference
EFO:0004980	appendicular lean mass
EFO:0004509	hemoglobin measurement
EFO:0007984	platelet component distribution width
EFO:0009188	Red cell distribution width

MeSH disease descriptors (6)

Descriptor	Name	Tree numbers
D003398	Craniosynostoses	C05.116.099.370.894.232; C05.660.207.240; C05.660.906.364; C16.131.621.207.240; C16.131.621.906.364
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D007640	Keratoconus	C11.204.627
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
D065886	Neurodevelopmental Disorders	F03.625
C564816	Insulin-Like Growth Factor I, Resistance To (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL1957 (SINGLE PROTEIN), CHEMBL4748221 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

27 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 247,132 (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
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL1983268	ENTRECTINIB	4	3,510
CHEMBL2403108	CERITINIB	4	8,551
CHEMBL3545311	BRIGATINIB	4	5,634
CHEMBL477772	PAZOPANIB	4	15,540
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL535	SUNITINIB	4	79,020
CHEMBL601719	CRIZOTINIB	4	14,403
CHEMBL1091644	LINSITINIB	3	1,446
CHEMBL50	QUERCETIN	3	74,559
CHEMBL603469	LESTAURTINIB	3
CHEMBL1230609	FORETINIB	2	3,096
CHEMBL1967878	CENISERTIB	2	358
CHEMBL1980297	ILORASERTIB	2	581
CHEMBL475251	R-406	2	762
CHEMBL572878	TOZASERTIB	2	2,998
CHEMBL575448	BMS-754807	2	406
CHEMBL6246	ELLAGIC ACID	2	23,148
CHEMBL1084546	PF-00562271	1	399
CHEMBL1908397	KW-2449	1	622
CHEMBL3545085	XL-228	1
CHEMBL3545360	ASP-3026	1
CHEMBL3679680	NT-219	1
CHEMBL3899477	CONTELTINIB	1
CHEMBL4289017	PF-03814735	1
CHEMBL49120	PD-0166285	1
CHEMBL551064	AEW-541	1

Clinical evidence (CIViC)

Drug × variant × indication: 4 predictive associations from 4 curated evidence items.

Variant	Therapy	Indication	Effect	Level	CIViC
IGF1R NUCLEAR EXPRESSION	IGF1R Monoclonal Antibody	Sarcoma	Sensitivity/Response	CIViC B	EID924
IGF1R Overexpression	Exemestane + Metformin	Breast Cancer	Sensitivity/Response	CIViC B	EID10138
IGF1R Overexpression	Crizotinib + Gefitinib + Linsitinib	Salivary Gland Adenoid Cystic Carcinoma	Sensitivity/Response	CIViC D	EID9024
IGF1R EXPRESSION	Gefitinib	Lung Non-small Cell Carcinoma	Resistance	CIViC D	EID904

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2016347	IGF1R		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: catalytic receptor — Type II RTKs: Insulin receptor family

Most potent curated ligand interactions (17 total), top 17:

Ligand	Action	Affinity	Parameter
teprotumumab	Antagonist	12.16	pKd
NVP-AEW541	Inhibition	9.4	pIC50
picropodophyllin	Inhibition	9.0	pIC50
istiratumab	Binding	9.0	pKd
BMS-754807	Inhibition	8.7	pIC50
GSK-1838705A	Inhibition	8.15	pKd
ceritinib	Inhibition	8.1	pIC50
AZD3463	Inhibition	8.0	pIC50
brigatinib	Inhibition	7.61	pIC50
linsitinib	Inhibition	7.46	pIC50
BMS-536924	Inhibition	7.0	pIC50
NVP-TAE 226	Inhibition	6.85	pIC50
GSK1511931	Inhibition	6.6	pIC50
fexagratinib	Inhibition	6.24	pIC50
PQ401	Inhibition	6.0	pIC50
compound 19a [PMID: 30503936]	Inhibition	5.68	pIC50
AG 1024	Inhibition	4.74	pIC50

Binding affinities (BindingDB)

718 measured of 1140 human assays (1141 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
9-(2-chlorophenyl)-N-[2-methoxy-4-(2-pyrrolidin-1-ylethoxy)phenyl]-8-methyl-5,6-dihydropyrazolo[3,4-h]quinazolin-2-amine	IC50	0.18 nM	US-8735386: Aminopyrazoloquinazolines
9-(2-chlorophenyl)-N-[2-methoxy-4-(4-methylpiperazin-1-yl)phenyl]-5,8-dimethyl-5,6-dihydropyrazolo[3,4-h]quinazolin-2-amine	IC50	0.19 nM	US-8735386: Aminopyrazoloquinazolines
9-(2-chlorophenyl)-N-[2-methoxy-4-(4-methylpiperazin-1-yl)phenyl]-8-methyl-5,6-dihydropyrazolo[3,4-h]quinazolin-2-amine	IC50	0.19 nM	US-8735386: Aminopyrazoloquinazolines
1-[4-[4-[[9-(3-chlorothiophen-2-yl)-8-methyl-5,6-dihydropyrazolo[3,4-h]quinazolin-2-yl]amino]pyrazol-1-yl]piperidin-1-yl]ethanone	IC50	0.2 nM	US-8735386: Aminopyrazoloquinazolines
9-(4-chlorophenyl)-N-[1-(2-methoxyethyl)pyrazol-3-yl]-8-methyl-5,6-dihydropyrazolo[3,4-h]quinazolin-2-amine	IC50	0.2 nM	US-8735386: Aminopyrazoloquinazolines
9-benzyl-N-[2-ethoxy-4-(4-propan-2-ylpiperazin-1-yl)phenyl]-8-methyl-5,6-dihydropyrazolo[3,4-h]quinazolin-2-amine	IC50	0.26 nM	US-8735386: Aminopyrazoloquinazolines
4-[[9-(2-chlorophenyl)-8-methyl-5,6-dihydropyrazolo[3,4-h]quinazolin-2-yl]amino]-3-methoxy-N-(4-morpholin-4-ylcyclohexyl)benzamide	IC50	0.27 nM	US-8735386: Aminopyrazoloquinazolines
9-(2-chloro-4-methoxyphenyl)-N-[2-methoxy-4-(4-methylpiperazin-1-yl)phenyl]-8-methyl-5,6-dihydropyrazolo[3,4-h]quinazolin-2-amine	IC50	0.3 nM	US-8735386: Aminopyrazoloquinazolines
N-(1-ethylpyrazol-3-yl)-8-methyl-9-(3-methylthiophen-2-yl)-5,6-dihydropyrazolo[3,4-h]quinazolin-2-amine	IC50	0.3 nM	US-8735386: Aminopyrazoloquinazolines
9-(3-chlorothiophen-2-yl)-8-methyl-N-(1-methylpyrazol-4-yl)-5,6-dihydropyrazolo[3,4-h]quinazolin-2-amine	IC50	0.3 nM	US-8735386: Aminopyrazoloquinazolines
4-[[9-(3-chlorothiophen-2-yl)-8-methyl-5,6-dihydropyrazolo[3,4-h]quinazolin-2-yl]amino]-3-methoxy-N-(1-methylpiperidin-4-yl)benzamide	IC50	0.3 nM	US-8735386: Aminopyrazoloquinazolines
4-fluoro-2-[(2-{[2-methoxy-4-(1-propylpiperidin-4-yl)phenyl]amino}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]benzamide	IC50	0.3 nM
9-benzyl-N-[2-ethoxy-4-(4-methylpiperazin-1-yl)phenyl]-8-methyl-5,6-dihydropyrazolo[3,4-h]quinazolin-2-amine	IC50	0.31 nM	US-8735386: Aminopyrazoloquinazolines
4-[[9-(2-chloro-4-methoxyphenyl)-8-methyl-5,6-dihydropyrazolo[3,4-h]quinazolin-2-yl]amino]-3-methoxy-N-(1-methylpiperidin-4-yl)benzamide	IC50	0.4 nM	US-8735386: Aminopyrazoloquinazolines
9-(3-chlorothiophen-2-yl)-8-methyl-N-phenyl-5,6-dihydropyrazolo[3,4-h]quinazolin-2-amine	IC50	0.4 nM	US-8735386: Aminopyrazoloquinazolines
N-[1-[2-[4-(dimethylamino)piperidin-1-yl]ethyl]pyrazol-3-yl]-8-methyl-9-phenyl-5,6-dihydropyrazolo[3,4-h]quinazolin-2-amine	IC50	0.4 nM	US-8735386: Aminopyrazoloquinazolines
1-[4-[4-[[9-(4-methoxyphenyl)-8-methyl-5,6-dihydropyrazolo[3,4-h]quinazolin-2-yl]amino]pyrazol-1-yl]piperidin-1-yl]ethanone	IC50	0.4 nM	US-8735386: Aminopyrazoloquinazolines
4-[[9-[(2-chlorophenyl)methyl]-8-methyl-5,6-dihydropyrazolo[3,4-h]quinazolin-2-yl]amino]-3-methoxy-N-(1-methylpiperidin-4-yl)benzamide	IC50	0.4 nM	US-8735386: Aminopyrazoloquinazolines
4-fluoro-2-[(2-{[2-methoxy-4-(1-propylpiperidin-3-yl)phenyl]amino}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]benzamide	IC50	0.4 nM
9-benzyl-N-[2-ethoxy-4-[4-(oxan-4-yl)piperazin-1-yl]phenyl]-8-methyl-5,6-dihydropyrazolo[3,4-h]quinazolin-2-amine	IC50	0.43 nM	US-8735386: Aminopyrazoloquinazolines
9-(2-chloro-4-methoxyphenyl)-N-[2-methoxy-4-(2-pyrrolidin-1-ylethoxy)phenyl]-8-methyl-5,6-dihydropyrazolo[3,4-h]quinazolin-2-amine	IC50	0.5 nM	US-8735386: Aminopyrazoloquinazolines
9-(3-chlorothiophen-2-yl)-N-[1-[2-(dimethylamino)ethyl]pyrazol-3-yl]-8-methyl-5,6-dihydropyrazolo[3,4-h]quinazolin-2-amine	IC50	0.5 nM	US-8735386: Aminopyrazoloquinazolines
1-[4-[4-[[8-methyl-9-[(2-methylphenyl)methyl]-5,6-dihydropyrazolo[3,4-h]quinazolin-2-yl]amino]pyrazol-1-yl]piperidin-1-yl]ethanone	IC50	0.5 nM	US-8735386: Aminopyrazoloquinazolines
9-[(3-chlorophenyl)methyl]-N-[2-methoxy-4-(4-propan-2-ylpiperazin-1-yl)phenyl]-8-methyl-5,6-dihydropyrazolo[3,4-h]quinazolin-2-amine	IC50	0.5 nM	US-8735386: Aminopyrazoloquinazolines
2-{[2-({5-[2-(dimethylamino)acetamido]-2-methoxy-4-methylphenyl}amino)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino}-6-fluorobenzamide	IC50	0.5 nM
4,5-difluoro-2-{[2-({2-methoxy-4-[4-(propan-2-yl)piperazin-1-yl]phenyl}amino)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino}benzamide	IC50	0.5 nM
4-[[9-(2-chlorophenyl)-8-methyl-5,6-dihydropyrazolo[3,4-h]quinazolin-2-yl]amino]-N-[1-(2-hydroxyethyl)piperidin-4-yl]-3-methoxybenzamide	IC50	0.54 nM	US-8735386: Aminopyrazoloquinazolines
4-[(9-benzyl-8-methyl-5,6-dihydropyrazolo[3,4-h]quinazolin-2-yl)amino]-3-ethoxy-N-(1-methylazetidin-3-yl)benzamide	IC50	0.57 nM	US-8735386: Aminopyrazoloquinazolines
2-[4-[2-[3-[(8-methyl-9-phenyl-5,6-dihydropyrazolo[3,4-h]quinazolin-2-yl)amino]pyrazol-1-yl]ethyl]piperazin-1-yl]ethanol	IC50	0.6 nM	US-8735386: Aminopyrazoloquinazolines
N-[1-[2-[4-(2-methoxyethyl)piperazin-1-yl]ethyl]pyrazol-3-yl]-8-methyl-9-phenyl-5,6-dihydropyrazolo[3,4-h]quinazolin-2-amine	IC50	0.6 nM	US-8735386: Aminopyrazoloquinazolines
1-[4-[4-[[8-methyl-9-(3-methylthiophen-2-yl)-5,6-dihydropyrazolo[3,4-h]quinazolin-2-yl]amino]pyrazol-1-yl]piperidin-1-yl]ethanone	IC50	0.6 nM	US-8735386: Aminopyrazoloquinazolines
9-(3-chlorothiophen-2-yl)-N-[1-(2-methoxyethyl)pyrazol-3-yl]-8-methyl-5,6-dihydropyrazolo[3,4-h]quinazolin-2-amine	IC50	0.6 nM	US-8735386: Aminopyrazoloquinazolines
9-(3-chlorothiophen-2-yl)-N-(1-ethylpyrazol-3-yl)-8-methyl-5,6-dihydropyrazolo[3,4-h]quinazolin-2-amine	IC50	0.6 nM	US-8735386: Aminopyrazoloquinazolines
8-methyl-9-phenyl-N-[1-(2-piperazin-1-ylethyl)pyrazol-3-yl]-5,6-dihydropyrazolo[3,4-h]quinazolin-2-amine	IC50	0.6 nM	US-8735386: Aminopyrazoloquinazolines
2-[(2-{[2-methoxy-4-(1-propyl-1,2,5,6-tetrahydropyridin-3-yl)phenyl]amino}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]benzamide	IC50	0.6 nM
9-benzyl-N-(2-ethoxy-4-piperazin-1-ylphenyl)-8-methyl-5,6-dihydropyrazolo[3,4-h]quinazolin-2-amine	IC50	0.63 nM	US-8735386: Aminopyrazoloquinazolines
N-[2-methoxy-4-(4-methylpiperazin-1-yl)phenyl]-8-methyl-9-[(1S)-1-phenylethyl]-5,6-dihydropyrazolo[3,4-h]quinazolin-2-amine	IC50	0.69 nM	US-8735386: Aminopyrazoloquinazolines
9-(3-chlorothiophen-2-yl)-N-[1-(2-methoxyethyl)pyrazol-4-yl]-8-methyl-5,6-dihydropyrazolo[3,4-h]quinazolin-2-amine	IC50	0.7 nM	US-8735386: Aminopyrazoloquinazolines
4-[[9-(2-chlorophenyl)-8-methyl-5,6-dihydropyrazolo[3,4-h]quinazolin-2-yl]amino]-N-[3-(dimethylamino)propyl]-3-methoxybenzamide	IC50	0.75 nM	US-8735386: Aminopyrazoloquinazolines
9-(2-chlorophenyl)-N-[2-methoxy-4-(2-pyrrolidin-1-ylethoxy)phenyl]-5,8-dimethyl-5,6-dihydropyrazolo[3,4-h]quinazolin-2-amine	IC50	0.8 nM	US-8735386: Aminopyrazoloquinazolines
4-fluoro-2-[(2-{[2-methoxy-4-(1-propyl-1,2,5,6-tetrahydropyridin-3-yl)phenyl]amino}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]benzamide	IC50	0.8 nM
4-fluoro-2-{[2-({2-methoxy-4-[4-(propan-2-yl)piperazin-1-yl]phenyl}amino)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino}benzamide	IC50	0.8 nM
5-fluoro-2-{[2-({2-methoxy-4-[4-(propan-2-yl)piperazin-1-yl]phenyl}amino)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino}benzamide	IC50	0.8 nM
2,4-difluoro-6-{[2-({2-methoxy-4-[4-(propan-2-yl)piperazin-1-yl]phenyl}amino)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino}benzamide	IC50	0.8 nM
4-[[9-(2-chlorophenyl)-8-methyl-5,6-dihydropyrazolo[3,4-h]quinazolin-2-yl]amino]-3-methoxy-N-(1-methylpiperidin-4-yl)benzamide	IC50	0.87 nM	US-8735386: Aminopyrazoloquinazolines
4-[[9-(2-chlorophenyl)-8-methyl-5,6-dihydropyrazolo[3,4-h]quinazolin-2-yl]amino]-3-methoxy-N-(1-methylazetidin-3-yl)benzamide	IC50	0.87 nM	US-8735386: Aminopyrazoloquinazolines
N-[2-methoxy-4-(4-methylpiperazin-1-yl)phenyl]-8-methyl-9-(2-methylphenyl)-5,6-dihydropyrazolo[3,4-h]quinazolin-2-amine	IC50	0.92 nM	US-8735386: Aminopyrazoloquinazolines
(2S,4S)-1-[4-[(5-cyclopropyl-1H-pyrazol-3-yl)amino]pyrrolo[2,1-f][1,2,4]triazin-2-yl]-4-hydroxy-N-pyridin-3-ylpyrrolidine-2-carboxamide	IC50	1 nM	US-8592579: Pyrrolotriazine kinase inhibitors
(2S,4R)-1-[4-[(5-cyclopropyl-1H-pyrazol-3-yl)amino]pyrrolo[2,1-f][1,2,4]triazin-2-yl]-N-(6-fluoro-3-pyridinyl)-4-methoxypyrrolidine-2-carboxamide	IC50	1 nM	US-8592579: Pyrrolotriazine kinase inhibitors
(2S,4S)-1-[4-[(5-cyclopropyl-1H-pyrazol-3-yl)amino]pyrrolo[2,1-f][1,2,4]triazin-2-yl]-N-(6-fluoro-3-pyridinyl)-4-methoxypyrrolidine-2-carboxamide	IC50	1 nM	US-8592579: Pyrrolotriazine kinase inhibitors

ChEMBL bioactivities

3436 potent at pChembl≥5 of 3545 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.30	IC50	0.05	nM	CHEMBL3905758
10.30	IC50	0.05	nM	CHEMBL3950012
10.10	IC50	0.08	nM	CHEMBL3928243
10.10	IC50	0.08	nM	CHEMBL3977170
10.10	IC50	0.08	nM	CHEMBL3979064
10.10	IC50	0.08	nM	CHEMBL3955626
10.05	IC50	0.09	nM	CHEMBL3896205
10.05	IC50	0.09	nM	CHEMBL3969930
10.05	IC50	0.09	nM	CHEMBL3979509
10.00	IC50	0.1	nM	CHEMBL3892425
10.00	IC50	0.1	nM	CHEMBL3985408
10.00	IC50	0.1	nM	CHEMBL3916799
10.00	IC50	0.1	nM	CHEMBL3893323
10.00	IC50	0.1	nM	CHEMBL3952080
9.96	IC50	0.11	nM	CHEMBL3823268
9.96	IC50	0.11	nM	CHEMBL3961098
9.96	IC50	0.11	nM	CHEMBL3986353
9.92	IC50	0.12	nM	CHEMBL3921486
9.89	IC50	0.13	nM	CHEMBL3911964
9.89	IC50	0.13	nM	CHEMBL3965426
9.89	IC50	0.13	nM	CHEMBL3907737
9.89	IC50	0.13	nM	CHEMBL3939707
9.89	IC50	0.13	nM	CHEMBL3942607
9.89	IC50	0.13	nM	CHEMBL3947924
9.85	IC50	0.14	nM	CHEMBL3972210
9.85	IC50	0.14	nM	CHEMBL3958897
9.85	IC50	0.14	nM	CHEMBL3951322
9.85	IC50	0.14	nM	CHEMBL3946122
9.82	IC50	0.15	nM	CHEMBL3920050
9.82	IC50	0.15	nM	CHEMBL3976534
9.82	IC50	0.15	nM	CHEMBL3952388
9.80	IC50	0.16	nM	CHEMBL3967200
9.80	IC50	0.16	nM	CHEMBL3891732
9.80	IC50	0.16	nM	CHEMBL3977626
9.80	IC50	0.16	nM	CHEMBL3906800
9.80	IC50	0.16	nM	CHEMBL3969767
9.80	IC50	0.16	nM	CHEMBL3985256
9.80	IC50	0.16	nM	CHEMBL3950693
9.80	IC50	0.16	nM	CHEMBL3940776
9.80	IC50	0.16	nM	CHEMBL3928015
9.77	IC50	0.17	nM	CHEMBL3982422
9.77	IC50	0.17	nM	CHEMBL3962155
9.77	IC50	0.17	nM	CHEMBL3930224
9.77	IC50	0.17	nM	CHEMBL3959576
9.77	IC50	0.17	nM	CHEMBL3985755
9.74	IC50	0.18	nM	CHEMBL3652826
9.74	IC50	0.18	nM	CHEMBL3904495
9.74	IC50	0.18	nM	CHEMBL3956581
9.72	IC50	0.19	nM	CHEMBL3656563
9.72	IC50	0.19	nM	CHEMBL3656576

PubChem BioAssay actives

1943 with measured affinity, of 5752 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
2-[[5-chloro-2-(4-dimethylphosphoryl-2-methoxyanilino)pyrimidin-4-yl]amino]benzamide	1310802: Inhibition of human IGF1R using KKKSPGEYVNIEFG as substrate and [gamma-33P]ATP measured after 1 hr	ic50	0.0001	uM
3-[[2-[[1-[2-(dimethylamino)acetyl]-6-methoxy-3,4-dihydro-2H-quinolin-7-yl]amino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino]thiophene-2-carboxamide	392350: Inhibition of IGF1R	ic50	0.0002	uM
3-[[2-[[1-[2-(dimethylamino)acetyl]-6-methoxy-4,4-dimethyl-2,3-dihydroquinolin-7-yl]amino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino]thiophene-2-carboxamide	392350: Inhibition of IGF1R	ic50	0.0002	uM
5-chloro-2-N-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]-4-N-(2-propan-2-ylsulfonylphenyl)pyrimidine-2,4-diamine	1310802: Inhibition of human IGF1R using KKKSPGEYVNIEFG as substrate and [gamma-33P]ATP measured after 1 hr	ic50	0.0003	uM
3-[[2-[[1-[2-(dimethylamino)acetyl]-5-methoxy-2,3-dihydroindol-6-yl]amino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino]thiophene-2-carboxamide	392350: Inhibition of IGF1R	ic50	0.0003	uM
4-fluoro-2-[[2-[2-methoxy-4-(1-propylpiperidin-4-yl)anilino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino]benzamide	1798838: IGF-1R Inhibition Assay from Article 10.1016/j.bmcl.2008.11.046: “Discovery of 4,6-bis-anilino-1H-pyrrolo[2,3-d]pyrimidines: potent inhibitors of the IGF-1R receptor tyrosine kinase.”	ic50	0.0003	uM
3-[[2-[[1-[2-(dimethylamino)acetyl]-6-methoxy-3,4-dihydro-2H-quinolin-7-yl]amino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino]furan-2-carboxamide	392350: Inhibition of IGF1R	ic50	0.0003	uM
4-fluoro-2-[[2-[2-methoxy-4-(1-propylpiperidin-3-yl)anilino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino]benzamide	1798838: IGF-1R Inhibition Assay from Article 10.1016/j.bmcl.2008.11.046: “Discovery of 4,6-bis-anilino-1H-pyrrolo[2,3-d]pyrimidines: potent inhibitors of the IGF-1R receptor tyrosine kinase.”	ic50	0.0004	uM
5-chloro-2-N-(4-dimethylphosphoryl-2-methoxyphenyl)-4-N-(2-methylsulfonylphenyl)pyrimidine-2,4-diamine	1310802: Inhibition of human IGF1R using KKKSPGEYVNIEFG as substrate and [gamma-33P]ATP measured after 1 hr	ic50	0.0004	uM
2-[[2-[5-[[2-(dimethylamino)acetyl]amino]-2-methoxy-4-methylanilino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino]-6-fluorobenzamide	1798832: IGF-1R Inhibition Assay from Article 10.1016/j.bmcl.2008.11.077: “Optimization of 4,6-bis-anilino-1H-pyrrolo[2,3-d]pyrimidine IGF-1R tyrosine kinase inhibitors towards JNK selectivity.”	ic50	0.0005	uM
4,5-difluoro-2-[[2-[2-methoxy-4-(4-propan-2-ylpiperazin-1-yl)anilino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino]benzamide	1798838: IGF-1R Inhibition Assay from Article 10.1016/j.bmcl.2008.11.046: “Discovery of 4,6-bis-anilino-1H-pyrrolo[2,3-d]pyrimidines: potent inhibitors of the IGF-1R receptor tyrosine kinase.”	ic50	0.0005	uM
1-[7-[[4-(2,3-dihydroindol-1-yl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl]amino]-6-methoxy-3,4-dihydro-2H-quinolin-1-yl]-2-(dimethylamino)ethanone	392350: Inhibition of IGF1R	ic50	0.0005	uM
3-[[2-[[1-[2-(dimethylamino)acetyl]-6-methoxy-3,4-dihydro-2H-quinolin-7-yl]amino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino]pyridine-2-carboxamide	392350: Inhibition of IGF1R	ic50	0.0005	uM
1-[2-[[5-chloro-2-(4-dimethylphosphoryl-2-methoxyanilino)pyrimidin-4-yl]amino]phenyl]ethanone	1310802: Inhibition of human IGF1R using KKKSPGEYVNIEFG as substrate and [gamma-33P]ATP measured after 1 hr	ic50	0.0005	uM
2-[[2-[2-methoxy-4-(1-propyl-3,6-dihydro-2H-pyridin-5-yl)anilino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino]benzamide	1798838: IGF-1R Inhibition Assay from Article 10.1016/j.bmcl.2008.11.046: “Discovery of 4,6-bis-anilino-1H-pyrrolo[2,3-d]pyrimidines: potent inhibitors of the IGF-1R receptor tyrosine kinase.”	ic50	0.0006	uM
3-[8-amino-1-(4-ethoxy-2-phenylquinolin-7-yl)imidazo[1,5-a]pyrazin-3-yl]-1-methylcyclobutan-1-ol	760419: Inhibition of GST-tagged IGF-1R catalytic domain (unknown origin) using omnia Y peptide-12 as substrate assessed as inhibition of substrate phosphorylation preincubated for 24 hrs prior to substrate addition by fluorescence assay	ic50	0.0006	uM
4-fluoro-2-[[2-[2-methoxy-4-(4-propan-2-ylpiperazin-1-yl)anilino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino]benzamide	392350: Inhibition of IGF1R	ic50	0.0007	uM
3-[[2-[[1-[2-(dimethylamino)acetyl]-5-methoxy-2,3-dihydroindol-6-yl]amino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino]pyridine-2-carboxamide	392350: Inhibition of IGF1R	ic50	0.0007	uM
3-[8-amino-1-(4-methoxy-2-phenylquinolin-7-yl)imidazo[1,5-a]pyrazin-3-yl]-1-methylcyclobutan-1-ol	760419: Inhibition of GST-tagged IGF-1R catalytic domain (unknown origin) using omnia Y peptide-12 as substrate assessed as inhibition of substrate phosphorylation preincubated for 24 hrs prior to substrate addition by fluorescence assay	ic50	0.0007	uM
5-chloro-2-N-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]-4-N-(2-methylsulfonylphenyl)pyrimidine-2,4-diamine	1310802: Inhibition of human IGF1R using KKKSPGEYVNIEFG as substrate and [gamma-33P]ATP measured after 1 hr	ic50	0.0008	uM
4-fluoro-2-[[2-[2-methoxy-4-(1-propyl-3,6-dihydro-2H-pyridin-5-yl)anilino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino]benzamide	1798838: IGF-1R Inhibition Assay from Article 10.1016/j.bmcl.2008.11.046: “Discovery of 4,6-bis-anilino-1H-pyrrolo[2,3-d]pyrimidines: potent inhibitors of the IGF-1R receptor tyrosine kinase.”	ic50	0.0008	uM
5-fluoro-2-[[2-[2-methoxy-4-(4-propan-2-ylpiperazin-1-yl)anilino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino]benzamide	1798838: IGF-1R Inhibition Assay from Article 10.1016/j.bmcl.2008.11.046: “Discovery of 4,6-bis-anilino-1H-pyrrolo[2,3-d]pyrimidines: potent inhibitors of the IGF-1R receptor tyrosine kinase.”	ic50	0.0008	uM
2,4-difluoro-6-[[2-[2-methoxy-4-(4-propan-2-ylpiperazin-1-yl)anilino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino]benzamide	1798838: IGF-1R Inhibition Assay from Article 10.1016/j.bmcl.2008.11.046: “Discovery of 4,6-bis-anilino-1H-pyrrolo[2,3-d]pyrimidines: potent inhibitors of the IGF-1R receptor tyrosine kinase.”	ic50	0.0008	uM
1-[6-[[4-(2,3-dihydroindol-1-yl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl]amino]-5-methoxy-2,3-dihydroindol-1-yl]-2-(dimethylamino)ethanone	392350: Inhibition of IGF1R	ic50	0.0008	uM
7-[[2-[[1-[2-(dimethylamino)acetyl]-5-methoxy-2,3-dihydroindol-6-yl]amino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino]-2,3-dihydroisoindol-1-one	392350: Inhibition of IGF1R	ic50	0.0008	uM
3-[[2-[[1-[2-(dimethylamino)acetyl]-5-methoxy-2,3-dihydroindol-6-yl]amino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino]furan-2-carboxamide	392350: Inhibition of IGF1R	ic50	0.0008	uM
N-[1-[2-[4-(2-methoxyethyl)piperazin-1-yl]ethyl]pyrazol-3-yl]-2,5-dimethyl-1-phenyl-4,5-dihydropyrazolo[4,3-f]quinazolin-7-amine	1845574: Inhibition of human IGF1R expressed in mouse IGF1R knockout MEF cells	ic50	0.0010	uM
(2S)-1-[4-[(5-cyclopropyl-1H-pyrazol-3-yl)amino]pyrrolo[2,1-f][1,2,4]triazin-2-yl]-N-(6-fluoro-3-pyridinyl)pyrrolidine-2-carboxamide	502112: Inhibition of IGF1R in IGF1R-SAL cells	ic50	0.0010	uM
2-[[2-[[1-[2-(dimethylamino)acetyl]-5-methoxy-2,3-dihydroindol-6-yl]amino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino]-6-fluorobenzamide	1798832: IGF-1R Inhibition Assay from Article 10.1016/j.bmcl.2008.11.077: “Optimization of 4,6-bis-anilino-1H-pyrrolo[2,3-d]pyrimidine IGF-1R tyrosine kinase inhibitors towards JNK selectivity.”	ic50	0.0010	uM
2-[[2-[5-[[2-(dimethylamino)acetyl]amino]-2-methoxyanilino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino]-6-fluorobenzamide	1798832: IGF-1R Inhibition Assay from Article 10.1016/j.bmcl.2008.11.077: “Optimization of 4,6-bis-anilino-1H-pyrrolo[2,3-d]pyrimidine IGF-1R tyrosine kinase inhibitors towards JNK selectivity.”	ic50	0.0010	uM
2-fluoro-6-[[2-[[5-methoxy-1-(2-pyrrolidin-1-ylacetyl)-2,3-dihydroindol-6-yl]amino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino]benzamide	1798832: IGF-1R Inhibition Assay from Article 10.1016/j.bmcl.2008.11.077: “Optimization of 4,6-bis-anilino-1H-pyrrolo[2,3-d]pyrimidine IGF-1R tyrosine kinase inhibitors towards JNK selectivity.”	ic50	0.0010	uM
2-[[2-[[1-[2-(azetidin-1-yl)acetyl]-5-methoxy-2,3-dihydroindol-6-yl]amino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino]-6-fluorobenzamide	1798832: IGF-1R Inhibition Assay from Article 10.1016/j.bmcl.2008.11.077: “Optimization of 4,6-bis-anilino-1H-pyrrolo[2,3-d]pyrimidine IGF-1R tyrosine kinase inhibitors towards JNK selectivity.”	ic50	0.0010	uM
2-[[2-[[1-[2-(dimethylamino)acetyl]-6-methoxy-3,4-dihydro-2H-quinolin-7-yl]amino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino]-6-fluorobenzamide	1798832: IGF-1R Inhibition Assay from Article 10.1016/j.bmcl.2008.11.077: “Optimization of 4,6-bis-anilino-1H-pyrrolo[2,3-d]pyrimidine IGF-1R tyrosine kinase inhibitors towards JNK selectivity.”	ic50	0.0010	uM
2-fluoro-6-[[2-[[6-methoxy-1-(2-piperidin-1-ylacetyl)-3,4-dihydro-2H-quinolin-7-yl]amino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino]benzamide	1798832: IGF-1R Inhibition Assay from Article 10.1016/j.bmcl.2008.11.077: “Optimization of 4,6-bis-anilino-1H-pyrrolo[2,3-d]pyrimidine IGF-1R tyrosine kinase inhibitors towards JNK selectivity.”	ic50	0.0010	uM
2-[[2-[2-methoxy-4-(4-propan-2-ylpiperazin-1-yl)anilino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino]benzamide	1798838: IGF-1R Inhibition Assay from Article 10.1016/j.bmcl.2008.11.046: “Discovery of 4,6-bis-anilino-1H-pyrrolo[2,3-d]pyrimidines: potent inhibitors of the IGF-1R receptor tyrosine kinase.”	ic50	0.0010	uM
N-(2,6-difluorophenyl)-3-[3-[2-[3-[2-(dimethylamino)ethoxy]anilino]pyrimidin-4-yl]imidazo[1,2-a]pyridin-2-yl]benzamide	371373: Inhibition of GST-tagged IGF1R (957-1367) expressed in baculovirus by time-resolved fluorescence assay	ic50	0.0010	uM
N-(2,6-difluorophenyl)-3-[3-[2-[3-[(2S)-3-(dimethylamino)-2-hydroxypropoxy]anilino]pyrimidin-4-yl]imidazo[1,2-a]pyridin-2-yl]benzamide	371373: Inhibition of GST-tagged IGF1R (957-1367) expressed in baculovirus by time-resolved fluorescence assay	ic50	0.0010	uM
1-[2-[[5-chloro-2-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]anilino]pyrimidin-4-yl]amino]phenyl]ethanone	1310802: Inhibition of human IGF1R using KKKSPGEYVNIEFG as substrate and [gamma-33P]ATP measured after 1 hr	ic50	0.0013	uM
2,3-difluoro-6-[[2-[2-methoxy-4-(4-propan-2-ylpiperazin-1-yl)anilino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino]benzamide	1798838: IGF-1R Inhibition Assay from Article 10.1016/j.bmcl.2008.11.046: “Discovery of 4,6-bis-anilino-1H-pyrrolo[2,3-d]pyrimidines: potent inhibitors of the IGF-1R receptor tyrosine kinase.”	ic50	0.0013	uM
3-[[2-[2-methoxy-4-(1-propylpiperidin-4-yl)anilino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino]thiophene-2-carboxamide	392350: Inhibition of IGF1R	ic50	0.0013	uM
2-[[5-chloro-2-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]anilino]pyrimidin-4-yl]amino]benzamide	1310802: Inhibition of human IGF1R using KKKSPGEYVNIEFG as substrate and [gamma-33P]ATP measured after 1 hr	ic50	0.0014	uM
N-(2,6-difluorophenyl)-5-[3-[2-[5-ethyl-2-methoxy-4-[4-(4-methylsulfonylpiperazin-1-yl)piperidin-1-yl]anilino]pyrimidin-4-yl]imidazo[1,2-a]pyridin-2-yl]-2-methoxybenzamide	2166449: Inhibition of intracellular domain of GST-tagged IGF1R (957 to 1367 residues) (unknown origin) expressed in baculovirus expression system using biotin-aminohexyl-AEEEEYMMMMAKKKK-NH2 as substrate pre incubated for 6 hrs followed by substrate addition and measured after 2 hrs in presence of [gamma-33P]-ATP by liquid scintillation counting method	ki	0.0016	uM
2-[[2-[4-(1-propyl-3,6-dihydro-2H-pyridin-5-yl)anilino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino]benzamide	1798838: IGF-1R Inhibition Assay from Article 10.1016/j.bmcl.2008.11.046: “Discovery of 4,6-bis-anilino-1H-pyrrolo[2,3-d]pyrimidines: potent inhibitors of the IGF-1R receptor tyrosine kinase.”	ic50	0.0016	uM
2-[[2-[2-fluoro-4-(1-propyl-3,6-dihydro-2H-pyridin-5-yl)anilino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino]benzamide	1798838: IGF-1R Inhibition Assay from Article 10.1016/j.bmcl.2008.11.046: “Discovery of 4,6-bis-anilino-1H-pyrrolo[2,3-d]pyrimidines: potent inhibitors of the IGF-1R receptor tyrosine kinase.”	ic50	0.0016	uM
4-fluoro-2-[[2-[2-methoxy-4-(4-propylpiperazin-1-yl)anilino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino]benzamide	1798838: IGF-1R Inhibition Assay from Article 10.1016/j.bmcl.2008.11.046: “Discovery of 4,6-bis-anilino-1H-pyrrolo[2,3-d]pyrimidines: potent inhibitors of the IGF-1R receptor tyrosine kinase.”	ic50	0.0016	uM
4-fluoro-2-[[2-(2-methoxy-4-morpholin-4-ylanilino)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino]benzamide	1798838: IGF-1R Inhibition Assay from Article 10.1016/j.bmcl.2008.11.046: “Discovery of 4,6-bis-anilino-1H-pyrrolo[2,3-d]pyrimidines: potent inhibitors of the IGF-1R receptor tyrosine kinase.”	ic50	0.0016	uM
2-[[2-[5-chloro-2-methoxy-4-(4-propan-2-ylpiperazin-1-yl)anilino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino]-6-fluorobenzamide	1798838: IGF-1R Inhibition Assay from Article 10.1016/j.bmcl.2008.11.046: “Discovery of 4,6-bis-anilino-1H-pyrrolo[2,3-d]pyrimidines: potent inhibitors of the IGF-1R receptor tyrosine kinase.”	ic50	0.0016	uM
3-[[2-[2-methoxy-4-(4-propan-2-ylpiperazin-1-yl)anilino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino]thiophene-2-carboxamide	392350: Inhibition of IGF1R	ic50	0.0016	uM
(2S)-1-[4-[(5-cyclopropyl-1H-pyrazol-3-yl)amino]pyrrolo[2,1-f][1,2,4]triazin-2-yl]-N-(6-fluoro-3-pyridinyl)-2-methylpyrrolidine-2-carboxamide	1533343: Inhibition of IGF-1R (unknown origin)	ic50	0.0018	uM
2-[[5-chloro-2-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]anilino]pyrimidin-4-yl]amino]-N,N-dimethylbenzenesulfonamide	1310802: Inhibition of human IGF1R using KKKSPGEYVNIEFG as substrate and [gamma-33P]ATP measured after 1 hr	ic50	0.0019	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Estradiol	decreases reaction, affects cotreatment, increases expression, decreases expression, affects binding (+2 more)	15
bisphenol A	increases expression, affects cotreatment, decreases methylation, decreases expression, increases methylation (+1 more)	8
Valproic Acid	affects expression, increases methylation, affects cotreatment, increases expression	7
Resveratrol	decreases phosphorylation, decreases reaction, increases expression, affects binding, increases activity (+2 more)	6
Benzo(a)pyrene	increases phosphorylation, decreases expression	5
Cadmium Chloride	decreases expression, increases abundance, increases expression, increases phosphorylation, affects reaction (+2 more)	5
Fulvestrant	increases reaction, affects cotreatment, decreases methylation, increases expression, increases phosphorylation (+2 more)	4
Quercetin	affects cotreatment, affects phosphorylation, affects reaction, decreases expression	4
Tetrachlorodibenzodioxin	decreases expression, increases expression, increases phosphorylation	4
methylmercuric chloride	increases expression, affects cotreatment	3
sodium arsenite	decreases reaction, increases phosphorylation, decreases expression, increases abundance	3
Cadmium	affects binding, increases reaction, increases expression, decreases expression, increases abundance	3
Cisplatin	increases reaction, decreases response to substance, decreases expression	3
Curcumin	decreases phosphorylation, increases reaction, decreases expression, decreases reaction, increases activity (+1 more)	3
Glucose	decreases reaction, increases expression, decreases expression	3
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	3
epigallocatechin gallate	increases expression, affects cotreatment, decreases expression	2
deguelin	decreases expression	2
picropodophyllin	decreases activity, decreases reaction, increases phosphorylation	2
tyrphostin AG 1024	affects binding, decreases reaction, increases reaction, increases phosphorylation	2
Insulin Glargine	increases activity, increases phosphorylation	2
Arsenic Trioxide	decreases expression, increases expression, affects response to substance	2
Ethanol	decreases expression	2
Arsenic	affects methylation, decreases expression, increases abundance	2
Calcitriol	affects expression, increases expression, affects cotreatment	2
Doxorubicin	decreases expression, decreases response to substance	2
Hexachlorobenzene	decreases reaction, increases expression, increases phosphorylation, affects cotreatment	2
Masoprocol	decreases reaction, increases expression, increases activity, increases phosphorylation, increases reaction (+1 more)	2
Polycyclic Aromatic Hydrocarbons	affects expression, affects cotreatment, increases abundance, increases expression	2
Dihydrotestosterone	increases expression, decreases reaction	2

ChEMBL screening assays

1091 unique, capped per target: 1037 binding, 53 functional, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1003897	Binding	Inhibition of IGF1R	Discovery of pyrrolopyridine-pyridone based inhibitors of Met kinase: synthesis, X-ray crystallographic analysis, and biological activities. — J Med Chem
CHEMBL1177072	Functional	Antagonist activity at human IGF1R expressed in mouse NIH/3T3 cells assessed as inhibition of IGF-induced cytoprotection at 20 uM by MTT assay relative to IGF	Bivalent diketopiperazine-based tropomysin receptor kinase C (TrkC) antagonists. — J Med Chem
CHEMBL4424885	ADMET	Inhibition of human N-terminal His6-tagged IGF1R (959 to end residues) expressed in baculovirus infected Sf21 insect cells	Optimization of an azetidine series as inhibitors of colony stimulating factor-1 receptor (CSF-1R) Type II to lead to the clinical candidate JTE-952. — Bioorg Med Chem Lett

Cellosaurus cell lines

18 cell lines: 13 cancer cell line, 3 transformed cell line, 2 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_6493	H19-7/IGF-IR	Transformed cell line	Sex unspecified
CVCL_8389	OCUM-8	Cancer cell line	Female
CVCL_B1UB	Abcam HeLa IGF1R KO	Cancer cell line	Female
CVCL_B8I0	Abcam HCT 116 IGF1R KO	Cancer cell line	Male
CVCL_B8X6	Abcam MCF-7 IGF1R KO	Cancer cell line	Female
CVCL_D206	NWT-21	Spontaneously immortalized cell line	Male
CVCL_D7RT	Ubigene A-549 IGF1R KO	Cancer cell line	Male
CVCL_D8MW	Ubigene HCT 116 IGF1R KO	Cancer cell line	Male
CVCL_D9GR	Ubigene HEK293 IGF1R KO	Transformed cell line	Female
CVCL_E0ER	Ubigene HeLa IGF1R KO	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age
NCT03222375	Not specified	RECRUITING	SQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism
NCT03229928	Not specified	COMPLETED	Clinical Testing of a Real-Time Behavior Measurement Tool: Measuring Outcomes for CHAnge
NCT03232489	Not specified	UNKNOWN	Study for the Evaluation of the Feasibility of Applying Advanced MRI Scanning in Pediatric Clinical Practice