GSK1838705A

GSK1838705A is an inhibitor of the insulin-like growth factor-1 receptor (IGF-1R) and the insulin receptor (IR, IC50s = 2 and 1.6 nM, respectively). It is selective for IGF-1R and IR over a panel of 47 kinases (IC50s = >1,600 nM), however, it also inhibits anaplastic lymphoma kinase (ALK, IC50 = 0.5 nM). GSK1838705A inhibits IGF-1 and insulin-induced phosphorylation of IGF-1R and IR in a concentration-dependent manner as well as phosphorylation of the downstream signaling markers Akt, IRS-1, and ERK in MCF-7 breast carcinoma cells. It inhibits growth in a panel of cancer cell lines (EC50s = 24-8,378 nM) with the IGF-1R signaling-dependent multiple myeloma and Ewing's sarcoma cell lines being the most sensitive. In vivo, GSK1838705A completely inhibits IGF-1-induced phosphorylation of IGF-1R, Akt, and IRS-1 as well as reduces tumor growth in the COLO 205 and NIH-3T2/LISN mouse xenograft models when administered at doses of >1 and >10 mg/kg, respectively. It also induces tumor cell apoptosis and reduces tumor growth in U87MG glioma and PC3R prostate cancer mouse xenograft models.Formal Name: 2-[[2-[[1-[2-(dimethylamino)acetyl]-2,3-dihydro-5-methoxy-1H-indol-6-yl]amino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino]-6-fluoro-N-methyl-benzamide. CAS Number: 1116235-97-2. Molecular Formula: C27H29FN8O3. Formula Weight: 532.6. Purity: >95%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 25 mg/ml, DMSO: 33 mg/ml, DMSO:PBS(pH 7.2) (1:3): 0.25 mg/ml, Ethanol: 2 mg/ml. lambdamax: 286, 327 nm. SMILES: FC1=CC=CC(NC2=C(C=CN3)C3=NC(NC4=CC(N(C(CN(C)C)=O)CC5)=C5C=C4OC)=N2)=C1C(NC)=O. InChi Code: InChI=1S/C27H29FN8O3/c1-29-26(38)23-17(28)6-5-7-18(23)31-25-16-8-10-30-24(16)33-27(34-25)32-19-13-20-15(12-21(19)39-4)9-11-36(20)22(37)14-35(2)3/h5-8,10,12-13H,9,11,14H2,1-4H3,(H,29,38)(H3,30,31,32,33,34). InChi Key: HZTYDQRUAWIZRE-UHFFFAOYSA-N.