MGCD-265

MGCD-265 is an inhibitor of c-Met and VEGFR2 (IC50s = 0.029 and 0.01 µM, respectively). It is selective for c-Met and VEGFR2 over Chk1, EGFR, GSK3beta, IGF-1R, IKKbeta, JAK2, and JNK1 at 0.1 µM but also inhibits VEGFR1, VEGFR3, Ron, Tie2, FLT3, c-Kit, Abl, and TrkA with percent inhibition values ranging from 80 to 100% at 0.1 µM. MGCD-265 also binds to Smoothened (Smo) in HEK293T cell membranes expressing the human receptor (Ki = 0.0417 µM for the wild-type receptor) and inhibits Gli1-mediated transcription in a reporter assay in gefitinib-resistant HCC827 non-small cell lung cancer (NSCLC) cells. It inhibits migration of A549 NSCLC cells induced by hepatocyte growth factor (HGF) and VEGF-induced proliferation of human umbilical vein endothelial cells (HUVECs, IC50s = 2 and 0.025 µM, respectively). MGCD-265 (20 mg/kg) reduces tumor growth in several mouse xenograft models, including prostate, colorectal, and gastric cancer models.Formal Name: N-[[[3-fluoro-4-[[2-(1-methyl-1H-imidazol-4-yl)thieno[3,2-b]pyridin-7-yl]oxy]phenyl]amino]thioxomethyl]-benzeneacetamide. CAS Number: 875337-44-3. Molecular Formula: C26H20FN5O2S2. Formula Weight: 517.6. Purity: >98%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 30 mg/ml, DMSO: 30 mg/ml, DMSO:PBS (pH 7.2)(1:5): 0.16 mg/ml. lambdamax: 258, 311 nm. SMILES: CN1C=C(N=C1)C2=CC3=NC=CC(=C3S2)OC4=C(C=C(C=C4)NC(=S)NC(=O)CC5=CC=CC=C5)F. InChi Code: InChI=1S/C26H20FN5O2S2/c1-32-14-20(29-15-32)23-13-19-25(36-23)22(9-10-28-19)34-21-8-7-17(12-18(21)27)30-26(35)31-24(33)11-16-5-3-2-4-6-16/h2-10,12-15H,11H2,1H3,(H2,30,31,33,35). InChi Key: UFICVEHDQUKCEA-UHFFFAOYSA-N.