PF-06843195

• CAT Number: I045427
• CAS Number: 2067281-51-8
• Molecular Formula: C20H25F3N8O4
• Molecular Weight: 498.46
• Purity: ≥95%
• Synonyms: 2,2-difluoroethyl (3S)-3-[[6-(2-aminopyrimidin-5-yl)-5-fluoro-2-morpholin-4-ylpyrimidin-4-yl]amino]-3-(hydroxymethyl)pyrrolidine-1-carboxylate
• InChI: InChI=1S/C20H25F3N8O4/c21-13(22)9-35-19(33)31-2-1-20(10-31,11-32)29-16-14(23)15(12-7-25-17(24)26-8-12)27-18(28-16)30-3-5-34-6-4-30/h7-8,13,32H,1-6,9-11H2,(H2,24,25,26)(H,27,28,29)/t20-/m0/s1
• InChIKey: RTOREZYNLPQUKM-FQEVSTJZSA-N
• SMILES: C1CN(CC1(CO)NC2=NC(=NC(=C2F)C3=CN=C(N=C3)N)N4CCOCC4)C(=O)OCC(F)F

PF-06843195 is a highly selective PI3Kα inhibitor with an IC50 of 18 nM in Rat1 fibroblasts. The Kis of PF-06843195 for PI3Kα and PI3Kδ in biochemical kinase assay are less than 0.018 nM and 0.28 nM, respectively. PF-06843195 has great suppression of the PI3K/mTOR signaling pathway and durable antitumor efficacy[1].
PF-06843195 inhibits the breast cancer cell lines MCF7 and T47D proliferation with IC50s of 62 nM and 32 nM, respectively[1].
PF-06843195 inhibits pAKT (T308) in MCF7 and T47D cells with IC50s of 7.8 nM and 8.7 nM, respectively[1].
In rats, PF-06843195 can rapidly and quantitatively transform from PF-06862309[1].
PF-06843195 exhibits oral bioavailability (rat 25 %) following oral administration (rat 10 mg/kg)[1].
PF-06843195 exhibits a moderate half-life (rat 3.6 h) due to high plasma clearance (30 mL/min/kg) combined with large volumes of distribution (3.0 L/kg) following intravenous administration (rat 2 mg/kg)[1].

Reference

[1]. Hengmiao Cheng, et al. Structure-Based Drug Design and Synthesis of PI3Kα-Selective Inhibitor (PF-06843195). J Med Chem. 2021 Jan 14;64(1):644-661.
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