CYH33 methanesulfonate

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

CYH33 (CYH-33) 是一种新型有效的 PI3Kα 选择性抑制剂，针对 I 类 PI3K 异构体 α/β/δ/γ 的 IC50 分别为 5.9 nM/598 nM/ 78.7 nM/225 nM。

CYH33 (CYH-33) is a novel potent, PI3Kα-selective inhibitor with IC50 of 5.9 nM/598 nM/ 78.7 nM/225 nM aginst class I PI3K isoform α/β/δ/γ, respectively; also displays little to no activity against more than 300 kinases; inhibits PI3K/AKT/mTOR signaling in glioblastoma U87MG and rhabdomyosarcoma Rh30 cells, shows potent anti-proliferative activity in against cell proliferation in a panel cancer cell lines originated from breast, lung, ovary and colon, prostate etc.; shows significant efficacy to inhibit the growth of SKOV-3 xenograft.Solid Tumors Phase 1 Clinical

CYH33 methanesulfonate inhibits cell proliferation with IC50s below 1?μM in 56% (18/32) of the breast cancer cell lines. CYH33 (0.012-1 μM; for 24 hours) methanesulfonate significantly arrests T47D and MCF7 cells in G1 phase in a concentration-dependent manner. CYH33 (4-1000 nM; 1 hour) methanesulfonate concurrently inhibits phosphorylation of ERK and Akt in both T47D and MCF7 cells. CYH33 (0.11-1 μM; 24 hours) methanesulfonate fails to induce apoptosis in MCF7 and MDA-MB-231?cells. Cell Cycle Analysis 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 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. 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. 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-Pik3caH1047R;MMTV-Cre mice. Animal Model:SCID mice aged 4-6 weeks bearing human breast cancer T47D xenografts 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.

CYH-33 methanesulfonate | HH-CYH33

PI3K/Akt/mTOR signaling

PI3K

PI3K

Cancer

Solid Tumors

1494684-33-1

694.702

C25H33F3N8O8S2

>98% (HPLC)

In Vitro:?DMSO : 200 mg/mL (287.89 mM)

COC(=O)NC1=NC=C(C(=C1)C(F)(F)F)C2=NN3C=C(C=C3C(=N2)N4CCOCC4)CN5CCN(CC5)S(=O)(=O)C.CS(=O)(=O)O

methyl (5-(6-((4-(methylsulfonyl)piperazin-1-yl)methyl)-4-morpholinopyrrolo[2,1-f][1,2,4]triazin-2-yl)-4-(trifluoromethyl)pyridin-2-yl)carbamate methanesulfonate

(-20℃)

With Ice Pack

≥ 2 years