| Identification | Back Directory | [Name]
1-Pyrrolidinecarboxylic acid, 3-[[2'-amino-5-fluoro-2-(4-morpholinyl)[4,5'-bipyrimidin]-6-yl]amino]-3-(hydroxymethyl)-, 2,2-difluoroethyl ester, (3S)- | [CAS]
2067281-51-8 | [Synonyms]
PF-06843195
1-Pyrrolidinecarboxylic acid, 3-[[2'-amino-5-fluoro-2-(4-morpholinyl)[4,5'-bipyrimidin]-6-yl]amino]-3-(hydroxymethyl)-, 2,2-difluoroethyl ester, (3S)- | [Molecular Formula]
C20H25F3N8O4 | [MDL Number]
MFCD34471099 | [MOL File]
2067281-51-8.mol | [Molecular Weight]
498.46 |
| Chemical Properties | Back Directory | [Boiling point ]
772.0±70.0 °C(Predicted) | [density ]
1.487±0.06 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
DMSO: 2mg/mL, clear | [form ]
Solid | [pka]
14.93±0.10(Predicted) | [color ]
White to off-white |
| Hazard Information | Back Directory | [Uses]
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]. | [Biological Activity]
PF-06843195 is a potent and PI3K-alpha subtype-selective phosphoinositide 3-kinase (PI3K) inhibitor (r at PI3K Ki = 2 nM/β<18 nM/α<280 nM/δ) th at inhibits cellular PI3Kα activity at a higher potency over th at of PI3Kδ/β and mTOR (AKT pT308 IC50 = 18/160/360 nM in r at PI3Kα/δ/β Rat1 lines; p70S6K pT389 IC50 = 1.5 μM in Rat1 myristoylated PI3K line). PF-06843195 is more potent against cellular AKT pT308 (MCF7/T47D IC50 = 7.8/8.7 nM) and proliferation (MCF7/T47D = 62/32 nM) than alpelisib (BYL719) in cultures. | [in vivo]
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]. | Animal Model: | Male Wistar Han Rats
[1] | | Dosage: | 2 mg/kg (intravenous) and 10 mg/kg (oral gavage)(Pharmacokinetic Analysis) | | Administration: | Intravenous (IV) or oral gavage (PO) | | Result: | T1/2 of 3.6 h for rats. |
| [IC 50]
PI3Kα: 18 nM (IC50, in Rat1 fibroblasts); PI3Kβ: 360 nM (IC50, in Rat1 fibroblasts); PI3Kδ: 160 nM (IC50, in Rat1 fibroblasts); PI3Kα: 0.018 nM (Ki); PI3Kδ: 0.28 nM (Ki) | [storage]
Store at -20°C | [References]
[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. DOI:10.1021/acs.jmedchem.0c01652 |
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| Company Name: |
Merck KGaA
|
| Tel: |
21-20338288 |
| Website: |
www.sigmaaldrich.cn |
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