PF-3758309 hydrochloride

Research use only, not for human use.

PF-3758309, also known as PF-03758309, is a PAK4 inhibitor, is also a n orally bioavailable small-molecule inhibitor of p21-activated kinase 4 (PAK4) with potential antineoplastic activity.

PF-3758309, also known as PF-03758309, is a PAK4 inhibitor, is also a n orally bioavailable small-molecule inhibitor of p21-activated kinase 4 (PAK4) with potential antineoplastic activity. PAK4 inhibitor PF-03758309 binds to PAK4, inhibiting PAK4 activity and cancer cell growth. PAK4, a serine/threonine kinase belonging to the p21-activated kinase (PAK) family, is often upregulated in a variety of cancer cell types and plays an important role in cancer cell motility, proliferation, and survival.(In Vitro):PF-3758309 has similar enzymatic potency against the kinase domains of the other group B PAKs (PAK5, Ki=18.1 nM; PAK6, Ki=17.1 nM) and group A PAK1 (Ki=13.7 nM), but is less active against the other two group A PAKs (PAK2, IC50=190 nM; PAK3, IC50=99 nM).In cells, PF-3758309 inhibits phosphorylation of the PAK4 substrate GEF-H1 (IC50=1.3 nM) and anchorage-independent growth of a panel of tumor cell lines (IC50=4.7 nM).PF-3758309 also inhibits endogenous pGEF-H1 accumulation in HCT116 cells. PF-3758309 potently inhibits cellular proliferation (IC50=20 nM) and anchorage-independent growth (IC50=27 nM) of A549 cells.(In Vivo):PF-3758309 (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.

PF-3758309 hydrochloride has similar enzymatic potency against the kinase domains of the other group B PAKs (PAK5, Ki=18.1 nM; PAK6, Ki=17.1 nM) and group A PAK1 (Ki=13.7 nM), but is less active against the other two group A PAKs (PAK2, IC50=190 nM; PAK3, IC50=99 nM). In cells, PF-3758309 hydrochloride inhibits phosphorylation of the PAK4 substrate GEF-H1 (IC50=1.3 nM) and anchorage-independent growth of a panel of tumor cell lines (IC50=4.7 nM). PF-3758309 hydrochloride also inhibits endogenous pGEF-H1 accumulation in HCT116 cells. PF-3758309 potently inhibits cellular proliferation (IC50=20 nM) and anchorage-independent growth (IC50=27 nM) of A549 cells.

PF-3758309 hydrochloride (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. Animal Model:Female nu/nu, CRL breed 6–8 weeks old mice (bearing HCT116 and A549 tumors) 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.

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Others

Other Targets

PAK4| PAK1| PAK6| PAK5| PAK3

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1279034-84-2

527.08

C25H31ClN8OS

>98% (HPLC)

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Cl.CN(C)C[C@@H](NC(=O)N1Cc2c(n[nH]c2Nc2nc(C)nc3ccsc23)C1(C)C)c1ccccc1

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(-20℃)

With Ice Pack

≥ 2 years