Physicochemical Properties
| Molecular Formula | C20H25F3N8O4 |
| Molecular Weight | 498.4589 |
| Exact Mass | 498.195 |
| CAS # | 2067281-51-8 |
| PubChem CID | 124193915 |
| Appearance | White to off-white solid powder |
| LogP | 0.4 |
| Hydrogen Bond Donor Count | 3 |
| Hydrogen Bond Acceptor Count | 14 |
| Rotatable Bond Count | 8 |
| Heavy Atom Count | 35 |
| Complexity | 701 |
| Defined Atom Stereocenter Count | 1 |
| SMILES | FC1=C(C2=C([H])N=C(N([H])[H])N=C2[H])N=C(N2C([H])([H])C([H])([H])OC([H])([H])C2([H])[H])N=C1N([H])[C@]1(C([H])([H])O[H])C([H])([H])N(C(=O)OC([H])([H])C([H])(F)F)C([H])([H])C1([H])[H] |
| InChi Key | RTOREZYNLPQUKM-FQEVSTJZSA-N |
| InChi Code | 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 |
| Chemical Name | 2,2-difluoroethyl (3S)-3-[[6-(2-aminopyrimidin-5-yl)-5-fluoro-2-morpholin-4-ylpyrimidin-4-yl]amino]-3-(hydroxymethyl)pyrrolidine-1-carboxylate |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| ln Vitro | Breast cancer cell lines MCF7 and T47D are inhibited from proliferating by PF-06843195, with IC50 values of 62 nM and 32 nM, respectively[1]. In MCF7 and T47D cells, PF-06843195 suppresses pAKT (T308) with IC50 values of 7.8 nM and 8.7 nM, respectively [1]. |
| ln Vivo | In rats, PF-06843195 can be promptly and quantitatively transformed from PF-06862309 [1]. PF-06843195 displays oral bioavailability (25% in rat) following oral dosing (rat 10 mg/kg) [1]. PF-06843195 has an intermediate half-life (rat 3.6) due to high plasma clearance (30 mL/min/kg) and large volume of distribution (3.0 L/kg) following intravenous treatment (rat 2 mg/kg) hours)[1]. |
| Animal Protocol |
Animal/Disease Models: Male Wistar Han rat[1] Doses: 2 mg/kg (intravenous) and 10 mg/kg (po (oral gavage)) (pharmacokinetic/PK/PK analysis) Route of Administration: intravenous (iv) (iv)(IV) or po (oral gavage) Experimental Results: T1/2 rats were 3.6 hrs (hrs (hours)). |
| References |
[1]. Structure-Based Drug Design and Synthesis of PI3Kα-Selective Inhibitor (PF-06843195). J Med Chem. 2021 Jan 14;64(1):644-661. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~62.5 mg/mL (~125.39 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.17 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (4.17 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0062 mL | 10.0309 mL | 20.0618 mL | |
| 5 mM | 0.4012 mL | 2.0062 mL | 4.0124 mL | |
| 10 mM | 0.2006 mL | 1.0031 mL | 2.0062 mL |