ETP-46321

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

ETP-46321 是一种有效的、选择性的、口服生物可利用的双重 PI3K α/δ 抑制剂，IC50 为 2.3/14.2 nM。

ETP-46321 is a potent, selective, orally bioavailable dual PI3K α/δ inhibitor with IC50 of 2.3/14.2 nM, weakly inhibits p110β and p110γ with IC50 of 170 and 179 nM; shows highly selectivity versus mTOR and 288 representative kinases, also potently inhibits mutants PI3K α E542K, E545K, and H1047R with IC50 of ~2 nM, inhibits phosphorylation of AKT Ser473 in the U2OS cell line with IC50 of 8.3 nM; shows significant tumor growth inhibition and reduction of the tumor metabolic activity in a lung tumor mouse model driven by a K-RasG12V oncogenic mutation.(In Vitro):ETP-46321 is selected to be screened against other PI3K isoforms. ETP-46321 is more potent against isoform α (Kiapp=2.3 nM). ETP-4632, has been profiled and shown to be a potent PI3K α and δ inhibitor, highly selective versus mTOR and 288 representative kinases. ETP-46321 is also tested against three of the p110α mutant enzymes detected in human cancers (E542K, E545K and H1047R), being equipotent against these mutants when compared to the wild type protein (Kiapp=2.33, 1.77 and 1.89 nM for PI3Kα-H1047R, PI3Kα-E545K and PI3Kα-E542K, respectively). ETP-46321 inhibits the phosphorilation of AKT in U2OS cell line with an IC50 of 8.3 nM.(In Vivo):ETP-46321, is selected for in vivo studies based on its appealing pharmacokinetic profile in BALB-C mice, low in vivo Clearance (0.6 L/h/Kg) and good oral bioavailability (90%). ETP-46321 demonstrates a good pharmacokinetic profile in mice and is selected for preliminary in vivo evaluation in a lung tumor mouse model driven by a K-RasG12V oncogenic mutation, showing significant tumor growth inhibition, and reduction of the tumor metabolic activity as measured by positron emission tomography (PET) techniques.

ETP-46321 is selected to be screened against other PI3K isoforms. ETP-46321 is more potent against isoform α (Kiapp=2.3 nM). ETP-4632, has been profiled and shown to be a potent PI3K α and δ inhibitor, highly selective versus mTOR and 288 representative kinases. ETP-46321 is also tested against three of the p110α mutant enzymes detected in human cancers (E542K, E545K and H1047R), being equipotent against these mutants when compared to the wild type protein (Kiapp=2.33, 1.77 and 1.89 nM for PI3Kα-H1047R, PI3Kα-E545K and PI3Kα-E542K, respectively). ETP-46321 inhibits the phosphorilation of AKT in U2OS cell line with an IC50 of 8.3 nM.

ETP-46321, is selected for in vivo studies based on its appealing pharmacokinetic profile in BALB-C mice, low in vivo Clearance (0.6 L/h/Kg) and good oral bioavailability (90%). ETP-46321 demonstrates a good pharmacokinetic profile in mice and is selected for preliminary in vivo evaluation in a lung tumor mouse model driven by a K-RasG12V oncogenic mutation, showing significant tumor growth inhibition, and reduction of the tumor metabolic activity as measured by positron emission tomography (PET) techniques.

ETP 46321 | ETP46321

PI3K/Akt/mTOR signaling

PI3K

PI3K

Cancer

——

1252594-99-2

473.5519

C20H27N9O3S

>98% (HPLC)

DMSO: ≥ 33 mg/mL

NC1=NC=C(C2=CN3C(C(N4CCOCC4)=N2)=NC(CN5CCN(S(=O)(C)=O)CC5)=C3)C=N1

2-Pyrimidinamine, 5-[2-[[4-(methylsulfonyl)-1-piperazinyl]methyl]-8-(4-morpholinyl)imidazo[1,2-a]pyrazin-6-yl]-

(-20℃)

With Ice Pack

≥ 2 years