KG5

• CAT Number: I011151
• CAS Number: 877874-85-6
• Molecular Formula: C20H16F3N7OS
• Molecular Weight: 459.45
• Purity: ≥95%
• Synonyms: 2-methylsulfanyl-6-[4-[3-[3-(trifluoromethyl)anilino]-1H-1,2,4-triazol-5-yl]phenoxy]pyrimidin-4-amine
• InChI: InChI=1S/C20H16F3N7OS/c1-32-19-26-15(24)10-16(27-19)31-14-7-5-11(6-8-14)17-28-18(30-29-17)25-13-4-2-3-12(9-13)20(21,22)23/h2-10H,1H3,(H2,24,26,27)(H2,25,28,29,30)
• InChIKey: CMYHZFCJPORPHY-UHFFFAOYSA-N
• SMILES: CSC1=NC(=CC(=N1)OC2=CC=C(C=C2)C3=NC(=NN3)NC4=CC=CC(=C4)C(F)(F)F)N

KG5 is an orally active dual PDGFRβ and B-Raf allosteric inhibitor. KG5 also inhibits Flt3, KIT and c-Raf. KG5 has anticancer, antiangiogenic activities[1].
KG5 (Compound 6) inhibits vascular smooth muscle cells (VSMCs) and endothelial cells viability with EC50 values of 0.59 μM and 0.54 μM, respectively[1].
Compound 6 selectively blocks S338 phosphorylation, yet does not influence S259[1].
KG5 (Compound 6) inhibits only PDGFRα and β with Kds of 300 and 520 nM, respectively, and Flt3 and KIT at 52 and 170 nM, respectively[1].
KG5 (Compound 6; 5 μM) inhibits phosphorylation of MEK and ERK in endothelial cells stimulated with bFGF or VEGF[1].
KG5 (Compound 6; 100 mg/kg; oral administration; daily; for 26 days) treatment prevents tumor growth in an orthotopic renal cell carcinoma model[1].
KG5 (Compound 6; 50 mg/kg; i.p.; twice daily) treatment completely blocks angiogenesis relative to vehicle control in mice (injected with Matrigel containing bFGF). Pharmacokinetic analysis of the dose and formulation of KG5 used indicated a Cmax of 3.6 μg/mL, T1/2 of 11.5 h, and an area under the concentration time curve (AUC0-12h) of 14.7 μg•h/mL[1].
KG5 (Compound 6; 1 μM) disrupts a late step in angiogenesis during zebrafish embryogenesis[1].

Reference

[1]. Eric A Murphy, et al. Disruption of angiogenesis and tumor growth with an orally active drug that stabilizes the inactive state of PDGFRbeta/B-RAF. Proc Natl Acad Sci U S A. 2010 Mar 2;107(9):4299-304.
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