PF-3758309 hydrochloride is a potent, orally available, and reversible ATP-competitive inhibitor of PAK4 (Kd= 2.7 nM; Ki=18.7 nM). PF-3758309 hydrochloride has the expected cellular functions of a PAK4 inhibitor: inhibition of anchorage-independent growth, induction of apoptosis, cytoskeletal remodeling, and inhibition of proliferation.

Product information

CAS Number: 1279034-84-2

Molecular Weight: 527.08

Formula: C25H31ClN8OS

Chemical Name: (S)-N-(2-(dimethylamino)-1-phenylethyl)-6, 6-dimethyl-3-((2-methylthieno[3, 2-d]pyrimidin-4-yl)amino)-2, 6-dihydropyrrolo[3, 4-c]pyrazole-5(4H)-carboxamide hydrochloride

Smiles: Cl.CN(C)C[C@@H](NC(=O)N1CC2C(=NNC=2NC2=NC(C)=NC3C=CSC=32)C1(C)C)C1C=CC=CC=1

InChiKey: DZSGSCZKFHGJNK-FSRHSHDFSA-N

InChi: InChI=1S/C25H30N8OS.ClH/c1-15-26-18-11-12-35-20(18)23(27-15)29-22-17-13-33(25(2,3)21(17)30-31-22)24(34)28-19(14-32(4)5)16-9-7-6-8-10-16;/h6-12,19H,13-14H2,1-5H3,(H,28,34)(H2,26,27,29,30,31);1H/t19-;/m1./s1

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

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.

In Vivo:

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.

Products are for research use only. Not for human use.