AZD-5363

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

AZD5363 是一种新型吡咯并嘧啶衍生化合物，可抑制所有 AKT 异构体 (IC50 <10 nM)。

AZD5363, a novel pyrrolopyrimidine-derived compound, inhibits all AKT isoforms (IC50 <10 nM).(In Vitro):Capivasertib, a novel pyrrolopyrimidine-derived compound, inhibits all AKT isoforms with a potency of 10 nM or less. Capivasertib inhibits phosphorylation of these substrates with an IC50 value of 0.06 to 0.76 μM in the 3 cell lines. Capivasertib effectively inhibits phosphorylation of S6 and 4E-BP1 in these cell lines, whereas it increases phosphorylation of AKT at both ser473 and thr308. In BT474c cells, Capivasertib induces FOXO3a nuclear translocation with EC50 value of 0.69 μM; a concentration of 3 μM is sufficient to almost completely localize FOXO3a to the nucleus. AZD5363Capivasertibhibitor MK-2206 is much less active (IC50>30 μM).(In Vivo):Oral dosing of Capivasertib (AZD5363) to nude mice causes dose- and time-dependent reduction of PRAS40, GSK3β, and S6 phosphorylation in BT474c xenografts (PRAS40 phosphorylation EC50 ~0.1 μM total plasma exposure), reversible increases in blood glucose concentrations, and dose-dependent decreases in 2[18F]fluoro-2-deoxy-D-glucose (18F-FDG) uptake in U87-MG xenografts. Chronic oral dosing of Capivasertib caused dose-dependent growth inhibition of xenografts derived from various tumor types, including HER2+ breast cancer models. Capivasertib also significantly enhances the antitumor activity of RP-56976 and GW572016 in breast cancer xenografts.

Capivasertib, a novel pyrrolopyrimidine-derived compound, inhibits all AKT isoforms with a potency of 10 nM or less. Capivasertib inhibits phosphorylation of these substrates with an IC50 value of 0.06 to 0.76 μM in the 3 cell lines. Capivasertib effectively inhibits phosphorylation of S6 and 4E-BP1 in these cell lines, whereas it increases phosphorylation of AKT at both ser473 and thr308. In BT474c cells, Capivasertib induces FOXO3a nuclear translocation with EC50 value of 0.69 μM; a concentration of 3 μM is sufficient to almost completely localize FOXO3a to the nucleus.

Oral dosing of Capivasertib (AZD5363) to nude mice causes dose- and time-dependent reduction of PRAS40, GSK3β, and S6 phosphorylation in BT474c xenografts (PRAS40 phosphorylation EC50 ~0.1 μM total plasma exposure), reversible increases in blood glucose concentrations, and dose-dependent decreases in 2[18F]fluoro-2-deoxy-D-glucose (18F-FDG) uptake in U87-MG xenografts. Chronic oral dosing of Capivasertib caused dose-dependent growth inhibition of xenografts derived from various tumor types, including HER2+ breast cancer models. Capivasertib also significantly enhances the antitumor activity of RP-56976 and GW572016 in breast cancer xenografts.

AZD5363 | AZD-5363 | AZD 5363 | Capivasertib

PI3K/Akt/mTOR signaling

Akt

Akt1| Akt2| Akt3| ROCK2

Cancer

——

1143532-39-1

428.92

C21H25ClN6O2

>98% (HPLC)

DMSO: 86 mg/mL (200.5 mM)

O=C(C1(N)CCN(C2=C3C(NC=C3)=NC=N2)CC1)N[C@H](C4=CC=C(Cl)C=C4)CCO

(S)-4-amino-N-(1-(4-chlorophenyl)-3-hydroxypropyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamide

(-20℃)

With Ice Pack

≥ 2 years