GSK1904529A

• CAT Number: I000378
• CAS Number: 1089283-49-7
• Molecular Formula: C₄₄H₄₇F₂N₉O₅S
• Molecular Weight: 851.96
• Purity: ≥95%
• Target: IGF1R
• Solubility: DMSO 125 mg/ml; Water <1 mg/ml
• Storage: 3 years -20C powder
• IC50: 27/25 nM (IGF1R/IR) [1]
• InChI: InChI=1S/C44H47F2N9O5S/c1-5-28-26-35(38(60-3)27-36(28)53-19-15-30(16-20-53)52-21-23-54(24-22-52)61(4,57)58)49-44-47-17-14-34(48-44)42-40(50-39-11-6-7-18-55(39)42)29-12-13-37(59-2)31(25-29)43(56)51-41-32(45)9-8-10-33(41)46/h6-14,17-18,25-27,30H,5,15-16,19-
• InChIKey: MOSKATHMXWSZTQ-UHFFFAOYSA-N
• SMILES: CCC1=CC(=C(C=C1N2CCC(CC2)N3CCN(CC3)S(=O)(=O)C)OC)NC4=NC=CC(=N4)C5=C(N=C6N5C=CC=C6)C7=CC(=C(C=C7)OC)C(=O)NC8=C(C=CC=C8F)F

GSK1904529A is a selective inhibitor of IGF-1R and IR with IC50 of 27 nM and 25 nM, >100-fold more selective for IGF-1R/InsR than Akt1/2, Aurora A/B,B-Raf, CDK2, EGFR etc.IC50 value: 27/25 nM (IGF1R/IR) [1]Target: IGF1R/IRin vitro: GSK1904529A is a reversible, ATP-competitive inhibitor and has enzyme-inhibitor binding values against IGF-1R and IR with Ki of 1.6 nM and 1.3 nM, respectively. GSK1904529A potently inhibits the ligand-induced phosphorylation of IGF-1R and IR at concentrations above 0.01 μM, followed by blocking downstream signaling (AKT, IRS-1, and ERK). GSK1904529A potently inhibits NIH-3T3/LISN, TC-71, SK-N-MC, SK-ES RD-ES cells with IC50 of 60 nM, 35 nM, 43 nM, 61 nM and 62 nM, respectively. GSK1904529A also inhibits other multiple myeloma and Ewing/’s sarcoma cell lines including NCI-H929, MOLP-8, LP-1 and KMS-12-BM etc. GSK1904529A induces cell cycle arrest at the G1 phase in cell lines COLO 205, MCF-7, and NCI-H929, which are sensitive to GK1904529A [1].in vivo: GSK1904529A indicates 98% tumor growth inhibition in NIH-3T3/LISN tumor-bearing mice at a dose of 30 mg/kg (orally, twice-daily) and 75% in COLO 205 xenografts mice (once daily). Among HT29 and BxPC3 xenografts, GSK1904529A produces moderate tumor growth inhibition with no side effects at a dose of 30 mg/kg. Meanwhile, GSK1904529A shows minimal effects on blood glucose levels. GSK1904529A (~3.5 μM in blood) completely inhibits IGF-1R phosphorylation. GSK1904529A has been implicated in treatment of various IGF-1R-dependent tumors including prostate, colon, breast, pancreatic, ovarian, and sarcomas [1].

Reference

1:GSK1904529A, a Potent IGF-IR Inhibitor, Reverses MRP1-Mediated Multidrug Resistance. Gupta P, Xie M, Narayanan S, Wang YJ, Wang XQ, Yuan T, Wang Z, Yang DH, Chen ZS.J Cell Biochem. 2017 Mar 7. doi: 10.1002/jcb.25975. [Epub ahead of print] PMID: 28266043 2:GSK1904529A, an insulin-like growth factor-1 receptor inhibitor, inhibits glioma tumor growth, induces apoptosis and inhibits migration. Zhou Q, Zhang J, Cui Q, Li X, Gao G, Wang Y, Xu Y, Gao X.Mol Med Rep. 2015 Sep;12(3):3381-5. doi: 10.3892/mmr.2015.3869. Epub 2015 May 28. PMID: 26035416 Free PMC Article3:Antitumor activity of GSK1904529A, a small-molecule inhibitor of the insulin-like growth factor-I receptor tyrosine kinase. Sabbatini P, Rowand JL, Groy A, Korenchuk S, Liu Q, Atkins C, Dumble M, Yang J, Anderson K, Wilson BJ, Emmitte KA, Rabindran SK, Kumar R.Clin Cancer Res. 2009 May 1;15(9):3058-67. doi: 10.1158/1078-0432.CCR-08-2530. Epub 2009 Apr 21. PMID: 19383820 Free Article