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: Cat #: V4429 CAS #: 1844849-11-1 Purity ≥ 98%
Description: PF-06821497 (PF06821497) is a novel, potent, selective and orally bioactive Enhancer of Zeste Homolog 2 (EZH2) inhibitor with potential anticancer effects. It inhibits EZH2 with a Ki value<0.1 nM against mutant Y641N EZH2 and exhibits robust tumor growth inhibitory effect. PF-06821497 was designed via ligand-based and physicochemical-property-based strategies to address metabolic stability and thermodynamic solubility issues associated with previous lead compound 1. The new inhibitors incorporated an sp3hybridized carbon atom at the 7-position of the lactam moiety present in lead compound 1 as a replacement for a dimethylisoxazole group. This transformation enabled optimization of the physicochemical properties and potency compared to compound 1. Analysis of relationships between calculated log D (clogD) values and in vitro metabolic stability and permeability parameters identified a clogD range that afforded an increased probability of achieving favorable ADME data in a single molecule. Compound 23a exhibited the best overlap of potency and pharmaceutical properties as well as robust tumor growth inhibition in vivo and was therefore advanced as a development candidate (PF-06821497). A crystal structure of PF-06821497 in complex with the three-protein PRC2 complex enabled understanding of the key structural features required for optimal binding.
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| CAS No. | 1844849-11-1 |
|---|---|
| Storage | -20℃ for 3 years in powder form |
| -80℃ for 2 years in solvent |
| Protocol | In Vivo | PF-06821497 (compound 23a: 100 mg/kg, PO twice daily for 31 days) treatment results in significant inhibition of tumor growth, and the the tumor regressition effect can be sustained for another 40 days after the terminal administration[1]. PF-06821497 with the dose of 300 mg/kg has minimal impact on animal body weights[1]. Animal Model: Mice bearing Karpas-422 DLBCL tumor xenografts (which contain the Y641N EZH2 mutation)[1]. Dosage: 100 mg/kg and 300 mg/kg. Administration: PO twice daily for 31 days. Result: 100 mg/kg dose resulted in significant inhibition of tumor growth and 300 mg/kg dose minimal effected animal body weights |
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This equation is commonly abbreviated as: C1 V1 = C2 V2
- (1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
- (2) Be sure to add the solvent(s) in order.