Insulin Receptor Inhibitor

Linsitinib (OSI-906) is a potent, selective and orally bioavailable dual inhibitor of the IGF-1 receptor and insulin receptor (IR) with IC₅₀s of 35 and 75 nM, respectively.

CEP-14513 is an ALK inhibitor with an IC₅₀ of 4 nM. CEP-14513 also inhibits insulin receptor, VEGFR2, TIE2 and DLK kinases, but does not inhibit MET, IKKβ, or CDK1/2/5. CEP-14513 induces cancer cell apoptosis. CEP-14513 is applicable to research related to non-small cell lung cancer, anaplastic large cell lymphoma, inflammatory myofibroblastic tumor, and diffuse large B-cell lymphoma.

AGT-182 (HIRMab; SHP-631; TAK-531) is a brain-penetrating anti-human insulin receptor antibody and iduronate-2-sulfatase conjugation. AGT-182 can be used for the research of mucopolysaccharidosis type II (MPS II, Hunter syndrome).

ALK-IN-24 is an orally active ALK inhibitor with an IC₅₀ value of 1.7 nM. ALK-IN-24 also inhibits insulin receptor kinase with an IC₅₀ value of 6 nM. ALK-IN-24 suppresses the proliferation of lung adenocarcinoma cells. ALK-IN-24 inhibits ALK-driven tumor growth in xenograft mouse models. ALK-IN-24 can be used in research related to non-small cell lung cancer.

Ceritinib (LDK378) is a selective, orally bioavailable, and ATP-competitive ALK tyrosine kinase inhibitor with an IC₅₀ of 200 pM. Ceritinib also inhibits IGF-1R, InsR, and STK22D with IC₅₀ values of 8, 7, and 23 nM, respectively. Ceritinib shows great antitumor potency.

BMS-754807 is a potent and reversible IGF-1R/IR inhibitor (IC₅₀=1.8 and 1.7 nM, respectively; K_i=<2 nM for both). BMS-754807 also shows potent activities against Met, RON, TrkA, TrkB, AurA, and AurB with IC₅₀ values of 6, 44, 7, 4, 9, and 25 nM, respectively.

NVP-AEW541 (AEW541 ) is an orally active inhibitor of the insulin-like growth factor 1 receptor (IGF-1R) with an IC₅₀ value of 0.15 μM. NVP-AEW541 also inhibits InsR, IC₅₀ with a value of 0.14 μM. NVP-AEW541 has antitumor activity.

Ceritinib (LDK378) dihydrochloride is a selective, orally bioavailable and ATP-competitive ALK tyrosine kinase inhibitor with an IC₅₀ of 200 pM. Ceritinib dihydrochloride also inhibits IGF-1R, InsR, and STK22D with IC₅₀ values of 8, 7, and 23 nM, respectively. Ceritinib dihydrochloride shows great antitumor potency.

BMS-536924 is an orally active, competitive and selective insulin-like growth factor receptor (IGF-1R) kinase and insulin receptor (IR) inhibitor with IC₅₀s of 100 nM and 73 nM, respectively. BMS-536924 has anti-cancer activity.

I3IN-002 is a small-molecule RNA-binding protein IGF2BP3 inhibitor with an IC₅₀ value of approximately 2 μM in SEM cells. I3IN-002 interferes with interaction with m6 A-modified mRNAs, disrupting the stabilization of target genes (such as CDK6, MYC, and BCL2) to inhibit leukemic cell growth, induce cell cycle arrest, and promote apoptosis. I3IN-002 is promising for research of B-cell acute lymphoblastic leukemia.

NT157 (Tyrphostin NT157) is a selective IRS-1/2 inhibitor that induces Ser-phosphorylation and consequently the degradation of IRS-1/2. NT157 (Tyrphostin NT157) is a first-in-class anti-cancer agent that also targets Stat3 signaling pathway.

NVP-TAE 226 (TAE226) is a potent and ATP-competitive dual FAK and IGF-1R inhibitor with IC₅₀s of 5.5 nM and 140 nM, respectively. NVP-TAE 226 (TAE226) also effectively inhibits Pyk2 and insulin receptor (InsR) with IC₅₀s of 3.5 nM and 44 nM, respectively.

NVP-ADW742 (ADW742) is an orally active, selective IGF-1R tyrosine kinase inhibitor with an IC₅₀ of 0.17 μM. NVP-ADW742 inhibits insulin receptor (InsR) with an IC₅₀ of 2.8 μM. NVP-ADW742 induces pleiotropic antiproliferative/proapoptotic biologic sequelae in tumor cells.

AG1024 (Tyrphostin AG 1024) is a reversible, competitive and selective IGF-1R inhibitor with an IC₅₀ of 7 μM. AG1024 inhibits phosphorylation of IR (IC₅₀=57 μM). AG1024 induces apoptosis and has anti-cancer activity.

GSK1838705A is a potent and reversible IGF-IR and the insulin receptor inhibitor with IC₅₀s of 2.0 and 1.6 nM, respectively. It also inhibits ALK with an IC₅₀ of 0.5 nM.

GSK1904529A is a potent, selective, orally active, and ATP-competitive inhibitor of insulin-like growth factor-1 receptor (IGF-1R) and insulin receptor (IR), with IC₅₀s of 27 and 25 nM, respectively. GSK1904529A shows poor activity (IC₅₀>1 μM) in 45 other serine/threonine and tyrosine kinases. GSK1904529A exhibits anti-tumor activity.

IGF2BP1-IN-1 (Compound A11) is a IGF2BP1 inhibitor and inhibits downstream signaling. IGF2BP1-IN-1 binds to IGF2BP1 protein with a K_D value of 2.88 nM. IGF2BP1-IN-1 inhibits cancer cells proliferation (IC₅₀: 9 nM for A549 cell, 34 nM for HCT116). IGF2BP1-IN-1 induces cancer cell apoptosis. GF2BP1-IN-1 inhibits tumor growth in A549 xenograft mouse model.

NT219 is a potent and dual inhibitor of insulin receptor substrates 1/2 (IRS1/2) and STAT3. IRS1/2 and STAT3 are major signaling junctions regulated by various oncogenes. NT219 affects IRS1/2 degradation and inhibits STAT3 phosphorylation. NT219 has the potential for the research of cancer diseases.

IMP2-IN-1 (compound 4) is a potent IMP2 inhibitor with IC₅₀ value of 81.3~127.5 for IMP2 RNA sequence. IMP2-IN-1 reduces IMP2 in SW480 cells. IMP2-IN-1 significantly reduces the viability of both differentiated and non-differentiated Huh7 cells.

HNMPA-(AM)3 is a cell-permeable and selective insulin receptor tyrosine kinase inhibitor analog of HNMPA. HNMPA-(AM)3 greatly inhibits the ability of prothoracicotropic hormone (PTTH) to activate ERK phosphorylation and stimulate ecdysteroidogenesis. HNMPA-(AM)3 is also effective in inhibiting ecdysteroid production (IC₅₀=14.2 μM) and insulin receptor activity (IC₅₀ is 14.2 μM and 200 μM in mosquitoes and mammals, respectively).