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.

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, a Cucurbitacin B (HY-N0416) derivative, is a potent IGF2BP1 inhibitor (K_D = 2.88 nM). IGF2BP1-IN-1 binds directly to IGF2BP1, thereby inducing tumor cell cycle arrest, increasing apoptosis, and reducing autophagy. IGF2BP1-IN-1 can be used in research on NSLSC, colon, breast, liver, ovarian, pancreatic, and cervical cancers.

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).

IGF2BP3-IN-1 (Compound I3IN-122) is an IGF2BP3 (a RNA binding protein) inhibitor (IC₅₀: > 50 μM), and can be used for cancer research.

Glucosylceramide (Glucocerebrosides) (gaucher's spleen) is a glycosphingolipid and primary substrate of acid β-glycosidase, suppresses tyrosine phosphorylation of insulin receptor and IRS-1, disrupts insulin signaling cascade and triggers pancreatic β-cell dysfunction. Glucosylceramide (Gaucher's spleen) accumulates in rodents and induces obesity and insulin resistance, restores systemic glucose homeostasis and insulin sensitivity when synthesis is suppressed. Glucosylceramide (Gaucher's spleen) accumulates in the brain of chronic neuronopathic Gaucher disease mice with age and can be applied for research on insulin resistance, type 2 diabetes mellitus and chronic neuronopathic Gaucher disease.