| Description | CHMFL-PI3KD-317 is a highly potent, selective and orally active PI3Kδ inhibitor, with an IC50 of 6 nM, and exhibits over 10-1500 fold selectivity over other class I, II and III PIKK family isoforms, such as PI3Kα (IC50, 62.6 nM), PI3Kβ (IC50, 284 nM), PI3Kγ (IC50, 202.7 nM), PIK3C2A (IC50, >10000 nM), PIK3C2B (IC50, 882.3 nM), VPS34 (IC50, 1801.7 nM), PI4KIIIA (IC50, 574.1 nM) and PI4KIIIB (IC50, 300.2 nM). CHMFL-PI3KD-317 inhibits PI3Kδ-mediated Akt T308 phosphorylation in Raji cells, with an EC50 of 4.3 nM. CHMFL-PI3KD-317 has antiproliferative effects on cancer cells. |
| In vitro | CHMFL-PI3KD-317 对其他第I、II、III类PIKK家族成员具有超过10-1500倍的选择性，例如 PI3Kα（IC50, 62.6 nM）、PI3Kβ（IC50, 284 nM）、PI3Kγ（IC50, 202.7 nM）、PIK3C2A（IC50, >10000 nM）、PIK3C2B（IC50, 882.3 nM）、PI4KIIIA（IC50, 574.1 nM）以及PI4KIIIB（IC50, 300.2 nM）。CHMFL-PI3KD-317 对NALM-6、PF382、MV4-11、MOLM-13细胞和MOLM-14细胞显示有抗增殖效果，GI50分别为4.0、3.5、4.8、3.0、3.3 μM。 |
| In vivo | CHMFL-PI3KD-317能够抑制小鼠MOLM14肿瘤的生长。在斯普拉格-道利(Sprague-Dawley)大鼠中，CHMFL-PI3KD-317展现出良好的口服生物利用度和可接受的半衰期（T1/2 = 3.28小时）。 |
| Target activity | PI4KIIIB:300.2 nM, PI3Kγ:202.7 nM, PI3Kα:62.6 nM, PI4KIIIA:574.1 nM, PIK3C2B:882.3 nM, PI3Kβ:284 nM, VPS34:1801.7 nM, PI3Kδ:6 nM |
| molecular weight | 494.03 |
| Molecular formula | C21H24ClN5O3S2 |
| CAS | 2244992-76-3 |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year |
| Solubility | DMSO: 45 mg/mL (91.09 mM) |
| References | 1. Liang X, et al. Discovery of (S)-2-amino-N-(5-(6-chloro-5-(3-methylphenylsulfonamido)pyridin-3-yl)-4-methylthiazol-2-yl)-3-methylbutanamide (CHMFL-PI3KD-317) as a potent and selective phosphoinositide 3-kinase delta (PI3Kδ) inhibitor. Eur J Med Chem. 2018 Aug 5;156:831-846. |