PI3Kα-IN-9

PI3Kα-IN-9 (compound 27) is a selective, long-acting and oral active PI3Kα inhibitor with IC50 values of 4.4, 128, 146 and 153 nM for PI3Kα, PI3Kγ, PI3Kδ and PI3Kβ, respectively. PI3Kα-IN-9 has antiproliferative activity and induces apoptosis. PI3Kα-IN-9 can be used for cancer research[1].

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

Signaling Pathways >> PI3K/Akt/mTOR >> PI3K

PI3Kα:4.4 nM (IC50)

PI3Kβ:153 nM (IC50)

PI3Kδ:146 nM (IC50)

PI3Kγ:128 nM (IC50)

PI3Kα-IN-9 (compound 27) (0-8 μM; 72 hours; cancer cell lines) has antiproliferative activity and induces apoptosis[1]. PI3Kα-IN-9 (compound 27) (0-8 μM; MGC-803 cells) down-regulates the expression of PI3Kα protein, the proteins of PI3K downstream, p-AKT and p-P70S6 K[1]. Cell Viability Assay[1] Cell Line: MGC-803 (gastric cancer), SKOV-3 (ovarian cancer), PC-3(prostate cancer), MCF-7 (breast cancer), MDA-MB-231 (triple-negative breast cancer), HepG2 (liver cancer), RPMI8226 (multiple myeloma), K562 (chronic myeloid leukemia), U251 (glioma) and MOLT-4 (acute lymphoblastic leukemia) cell lines Concentration: 0-2 μM Incubation Time: 72 hours Result: Inhibited the growth of a variety of cancer cells with IC50 values ranging from 0.43 to 1.33 μM. Apoptosis Analysis[1] Cell Line: MGC-803 cells Concentration: 0, 2, 4 and 8 μM Incubation Time: 36 hours Result: Increased the percentage of apoptotic cells from 12.07 to 61.69% in a dose-dependent manner.

PI3Kα-IN-9 (compound 27) (1-10 mg/kg; p.o. and i.v.; for 24 hours; male Sprague-Dawley rat) has favorable stability (T1/2>10 h) and high bioavailability (130%)[1]. PI3Kα-IN-9 (compound 27) (30 mg/kg; p.o.; daily, for 3 weeks; male BALB/c nude mice) has antitumor activity and low cytotoxicity[1]. Animal Model: Male Sprague-Dawley rat[1] Dosage: 1 and 10 mg/kg Administration: Oral administration and intravenous injection; for 24 hours (Pharmacokinetic Analysis) Result: 1.19 parameters IV PO dose (mg/kg) 1 10 T1/2 (h) 6.29 ﹥10 Tmax (h) 0.003 9.33 Cmax (ng/mL) 454.7 2256.7 AUC0-t (ng·h/mL) 2237 36697 AUC0-∞ (ng·h/mL) 2922.4 38114.3 CL (mL/h/kg) 343 F % 130.4 Animal Model: Male BALB/c nude mice[1] Dosage: 30 mg/kg Administration: Oral administration; daily, for 3 weeks Result: Inhibited tumor growth with a tumor growth inhibition (TGI) rate of 41.5%.

[1]. Hou Y, et, al. Discovery of Novel Phosphoinositide-3-Kinase α Inhibitors with High Selectivity, Excellent Bioavailability, and Long-Acting Efficacy for Gastric Cancer. J Med Chem. 2022 Jul 14.