PF-3758309 dihydrochloride是一种有效的、口服的、可逆的 ATP 竞争性PAK4抑制剂 (Kd= 2.7 nM;Ki=18.7 nM)。PF-3758309 dihydrochloride 具有 PAK4 抑制剂的预期细胞功能：抑制锚定独立生长、诱导凋亡、细胞骨架重塑和抑制增殖。

PF-3758309 dihydrochloride is a potent, orally available, and reversible ATP-competitive inhibitor of PAK4 ( K d = 2.7 nM; K i =18.7 nM). PF-3758309 dihydrochloride has the expected cellular functions of a PAK4 inhibitor: inhibition of anchorage-independent growth, induction of apoptosis, cytoskeletal remodeling, and inhibition of proliferation [1] [2] [3].

PF-3758309 dihydrochloride has similar enzymatic potency against the kinase domains of the other group B PAKs (PAK5, K i =18.1 nM; PAK6, K i =17.1 nM) and group A PAK1 (K i =13.7 nM), but is less active against the other two group A PAKs (PAK2, IC 50 =190 nM; PAK3, IC 50 =99 nM) [1]. In cells, PF-3758309 dihydrochloride inhibits phosphorylation of the PAK4 substrate GEF-H1 (IC 50 =1.3 nM) and anchorage-independent growth of a panel of tumor cell lines (IC 50 =4.7 nM) [1]. PF-3758309 dihydrochloride also inhibits endogenous pGEF-H1 accumulation in HCT116 cells. PF-3758309 potently inhibits cellular proliferation (IC 50 =20 nM) and anchorage-independent growth (IC 50 =27 nM) of A549 cells [1].

PF-3758309 dihydrochloride (7.5-30 mg/kg; p.o.; twice daily for 9-18 days) results in statistically significant tumor growth inhibition (TGI) in HCT116 and A549 models [1]. Animal Model: Female nu/nu, CRL breed 6–8 weeks old mice (bearing HCT116 and A549 tumors) [1] Dosage: 7.5-30 mg/kg Administration: Oral administration; twice daily for 9-18 days Result: Significant tumor growth inhibition (TGI) in HCT116 and A549 models.

C25H32Cl2N8OS

563.55

(< 1 mg/ml refers to the product slightly soluble or insoluble )
Powder: -20°C for 3 years
In solvent: -80°C for 2 years