MK 2206 dihydrochloride

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

一种有效的口服活性 Akt 变构抑制剂，对 Akt1/Akt2 的 IC50 分别为 5/12 nM。

A potent, orally active allosteric Akt inhibitor with IC50 of 5/12 nM for Akt1/Akt2 respectively; shows 5-fold less potent against human Akt3 (IC50=65 nM); synergistically inhibits cell proliferation of human cancer cell lines in combination with erlotinib or lapatinib in vitro; suppresses the Akt phosphorylation that is induced by carboplatin and gemcitabine.Colon Cancer Phase 2 Clinical(In Vitro):MK-2206 dihydrochloride (MK-2206 (2HCl)) (0-10 μM; 72 and 96 hours) inhibits the nasopharyngeal carcinoma (NPC) cell lines CNE-1, CNE-2, HONE-1, and SUNE-1 proliferation in dose- and time-dependent manner.MK-2206 dihydrochloride (0-10 μM; 24 and 48 hours) results in a dose-dependent increase in the percentage of cells in G0/G1 phase and a concomitant reduction of cell numbers in S phase in CNE-2 and HONE-1 cells.MK-2206 dihydrochloride (0-10 μM; 24 hours) attenuates phosphorylation levels of PRAS40 and S6 in a dose-dependent manner. MK-2206 does not effect phosphorylation of GSKα/β and AKT.MK-2206 dihydrochloride (0-10 μM; 24 hours) increases the appearance of LC3-II in CNE-2 cells dose-dependently. Microtubule-associated protein 1 LC3 is an essential autophagy protein.(In Vivo):Both MK-2206 dihydrochloride (MK-2206 (2HCl)) doses (oral gavage; 480 mg/kg once a week and 240 mg/kg three times a week; for 2 weeks) can inhibit the growth of human CNE-2 xenografts in nude mice. No other obvious toxicity is observed in mice.MK-2206 dihydrochloride (orally; 120 mg/kg; alternate days; for 3 weeks) significantly inhibits tumor growth in 3-5 week old athymic nude mice with GEO colon carcinoma cells.

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Animal Model:Four- to 6-week-old male BALB/c nude mice with CNE-2 xenografts Dosage:240 mg/kg and 480 mg/kg Administration:Oral gavage; 240 mg/kg for three times a week; 480 mg/kg for once a week; for 2 weeks Result:Both doses inhibited the growth of human CNE-2 xenografts in nude mice.

MK-2206 dihydrochloride | MK2206 dihydrochloride

PI3K/Akt/mTOR signaling

Akt

Akt1|Akt2|Akt3

Cancer

Colon Cancer

1032350-13-2

480.389

C25H23Cl2N5O

>98% (HPLC)

DMSO

Cl.Cl.NC1(CCC1)C1=CC=C(C=C1)C1=C(C=C2C3=NNC(=O)N3C=CC2=N1)C1=CC=CC=C1

1,2,4-Triazolo[3,4-f][1,6]naphthyridin-3(2H)-one, 8-[4-(1-aminocyclobutyl)phenyl]-9-phenyl-, hydrochloride (1:2)

(-20℃)

With Ice Pack

≥ 2 years