CYH33 methanesulfonate is a highly selective and orally active inhibitor of PI3Kα, with IC50 values of 5.9 nM, 598 nM, 78.7 nM, and 225 nM against the α, β, δ, and γ isoforms, respectively. This compound effectively inhibits the phosphorylation of Akt and ERK, leading to a significant G1 phase arrest in breast cancer cells and non-small cell lung cancer (NSCLC) cells. Additionally, CYH33 methanesulfonate demonstrates potent activity against solid tumors.

PI3Kβ:598 nM (IC50), PI3Kα:5.9 nM (IC50), PI3Kγ:225 nM (IC50), PI3Kδ:78.7 nM (IC50)

CYH33 methanesulfonate inhibits cell proliferation with IC 50 s below 1?μM in 56% (18/32) of the breast cancer cell lines[2]. CYH33 (0.012-1 μM; for 24 hours) methanesulfonate significantly arrests T47D and MCF7 cells in G1 phase in a concentration-dependent manner[2]. CYH33 (4-1000 nM; 1 hour) methanesulfonate concurrently inhibits phosphorylation of ERK and Akt in both T47D and MCF7 cells[2]. CYH33 (0.11-1 μM; 24 hours) methanesulfonate fails to induce apoptosis in MCF7 and MDA-MB-231?cells[2]. Cell Cycle Analysis[2]Cell Line: Sensitive T47D, MCF7 and resistant MDA-MB-231 cells Concentration: 0.012, 0.037, 0.11, 0.33, 1 μM Incubation Time: For 24 hours Result: Arrested T47D and MCF7 cells in G1 phase in a concentration-dependent manner, accompanied with concomitant reduced cell population in S phase. Had little effect on cell cycle distribution in resistant MDA-MB-231?cells. Western Blot Analysis[2]Cell Line: Sensitive T47D, MCF7 and resistant MDA-MB-231 cells Concentration: 4, 12, 37, 111, 333, 1000 nM Incubation Time: 1 hour Result: Concurrently inhibited phosphorylation of ERK and Akt in both T47D and MCF7 cells, whereas it had little effect on phosphorylated ERK (pERK) in MDA-MB-231?cells up to 1?μM.

CYH33 (2-20 mg/kg; oral; once a day for 21 days) methanesulfonate potently restrains tumor growth in mice bearing human breast cancer cell xenografts[2]. Single administration of CYH33 (20?mg/kg; oral) methanesulfonate significantly down-regulates the level of phosphorylated Akt in tumor tissues, demonstrating the suppression of PI3K signaling in nude mice[2]. CYH33 (10?mg/kg; oral; once a day for 18-d or 20-d respectively) methanesulfonate delays the restoration of blood glucose and area under the curve (AUC) of blood glucose increased upon CYH33 treatment in T47D xenografts and R26-Pik3ca H1047R ;MMTV-Cre mice[2]. Animal Model: SCID mice aged 4-6 weeks bearing human breast cancer T47D xenografts[2]Dosage: 2, 5, 10, 20 mg/kg Administration: Oral; once a day for 21 days Result: Displayed marginal inhibitory effect on the tumor growth at lower doses (2 and 5?mg/kg) and significantly attenuated tumor growth at the dose of 10 or 20?mg/kg, yielding T/C values of 58.36% and 49.42% respectively.