FAK-IN-2

• CAT Number: I043886
• CAS Number: 2872588-02-6
• Molecular Formula: C28H31ClN8O3
• Molecular Weight: 563.05
• Purity: ≥95%
• Synonyms: 2-[[5-chloro-2-[4-[4-[(2R)-2-(prop-2-enoylamino)propanoyl]piperazin-1-yl]anilino]pyrimidin-4-yl]amino]-N-methylbenzamide
• InChI: InChI=1S/C28H31ClN8O3/c1-4-24(38)32-18(2)27(40)37-15-13-36(14-16-37)20-11-9-19(10-12-20)33-28-31-17-22(29)25(35-28)34-23-8-6-5-7-21(23)26(39)30-3/h4-12,17-18H,1,13-16H2,2-3H3,(H,30,39)(H,32,38)(H2,31,33,34,35)/t18-/m1/s1
• InChIKey: SQMGCXJZSMCVHC-GOSISDBHSA-N
• SMILES: CC(C(=O)N1CCN(CC1)C2=CC=C(C=C2)NC3=NC=C(C(=N3)NC4=CC=CC=C4C(=O)NC)Cl)NC(=O)C=C

FAK-IN-2 is a potent and orally active focal adhesion kinase (FAK) inhibitor, with anticancer activity (FAK IC50= 35 nM). FAK-IN-2 covalently inhibits the autophosphorylation of FAK in a dose-dependent manner, and inhibits the clone formation and migration of tumor cells, inducing apoptosis[1].
FAK-IN-2 (compound 11w) (0-5 μM; 72 hours) has high anti-proliferation activities on cancer cell lines, as well as certain toxicity on normal cell lines[1].
FAK-IN-2 (0-30 nM; 14 days) can remarkably affect HCT-116 cells clone formation in a dose-dependent manner[1].
FAK-IN-2 (10-500 nM; 24 and 48 hours) significantly inhibits the migration of HCT116 cells at both 24 h and 48 h in a dose-dependent manner[1].
FAK-IN-2 (0.001-10 μM; 4 and 24 hours) inhibits the phosphorylation of FAK and its downstream proteins from multiple pathways[1].
FAK-IN-2 (0.01-1 μM; 24 or 48 hours) induces strong cell cycle arrest at the G2/M phase and apoptosis[1].
FAK-IN-2 (5 and 15 mg/kg; 16 days; once daily) has potent antitumor effects in model mice with a dose-dependent manner without significant toxicity[1]
Pharmacokinetic Parameters of FAK-IN-2 in male Sprague-Dawley rats[1].

PO (5 mg/kg)
IV (5 mg/kg)

Cmax (μg/L)
239.87
2965.27

Tmax (h)
1.44
0.08

T1/2 (h)
4.70
7.57

Clz (L/h/kg)
9.92
2.19

AUC0-t (μg*h/L)
512.75
2439.06

F %
21.02%

Reference

[1]. Chen T, et al. Design, synthesis, and biological evaluation of novel covalent inhibitors targeting focal adhesion kinase. Bioorg Med Chem Lett. 2021;54:128433.
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