CHMFL-PI3KD-317

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^[1]. In Vitro: CHMFL-PI3KD-317 has antiproliferative effects, with GI₅₀s of 3.5?±?0.8, 4.0?±?0.9, 4.8?±?0.2, 3.3?±?0.2, 3.0?±?0.4 μM against PF382, NALM-6, MV4-11, MOLM-14 and MOLM-13 cells, respectively^[1]. In Vivo: CHMFL-PI3KD-317 (Compound 15i; 25, 50 and 100?mg/kg/day, p.o., for 14 days) inhibits the growth of the MOLM14 tumor in mice^[1].
CHMFL-PI3KD-317 shows favorable oral bioavailability and acceptable half-life (T_1/2?=?3.28?h) in Sprague-Dawley rats^[1].