ALM301 (C09-1101-988)

ALM301 is an orally active highly specific AKT inhibitor with IC 50 values of 0.13 µM, 0.09 µM and 2.75 µM for AKT1 , AKT2 and AKT3 , respectively. ALM301 inhibits AKT phosphorylation and modulates downstream signalling in vitro . ALM301 can inhibit cancer cell proliferation and tumor growthIn VitroALM301 (0.001-10 µM; 72 h) inhibits the proliferation of cancer cells, and PI3KCA-mutant MCF-7 cells is the most sensitive; increases sub-G0 population in a dose-dependent manner. ALM301 (1 µM; 1 h) inhibits AKT phosphorylation in MCF-7 and sustains up to 48 h, with an EC 50 value of 0.47 µM. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Cell Proliferation AssayCell Line: MCF-7, T47D, NCI-H460, HCT116 and other cancer cells Concentration: 0.001-10 µM Incubation Time: 72 h Result: Inhibited the proliferation of cancer cells, and PI3KCA-mutant MCF-7 cells was the most sensitive with an IC 50 of 2.25 µM. Western Blot AnalysisCell Line: MCF-7 Concentration: 0.001-10 µM Incubation Time: 1, 4, 24 and 48 h Result: Inhibited pAKT and pGSK3β at various concentrations and timepoints up to 48 h.In VivoALM301 (10, 30 and 100 mg/kg; p.o.; single dosage) inhibits pAKT S473 in tumors and suppresses tumor growth . ALM301 (3 or 10 mg/kg; p.o.; q.d. for 49 days) shows better tumor inhibition ability when combined with Tamoxifen (HY-13757A) . MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: BALB/c mice (bearing A549 xenografts) Dosage: 10, 30 and 100 mg/kg Administration: p.o.; single dosage Result: Increased total plasma concentrations dose-dependently that resulted in almost total abrogation of measurable pAKT S473 in tumors at all timepoints over 24 h. Exhibited the tumour growth inhibition (TGI) of 23, 31 and 41% at 10, 30 and 100 mg/kg, respectively. Animal Model: BALB/c mice (bearing PIK3CA-mutant MCF-7 xenografts) Dosage: 3 or 10 mg/kg Administration: p.o.; q.d. for 49 days Result: Showed significant tumour regressions of 57% and 50% at 3 and 10 mg/kg, respectively, when combined with Tamoxifen (HY-13757A) (5 mg/kg; q.d.).Form:SolidIC50& Target:AKT1 0.13 μM (IC 50 ) Akt2 0.09 μM (IC 50 ) Akt3 2.75 μM (IC 50 ). Specifications and Purity: 99%. Molecular Formula: C25H25N3O3. Molecular Weight: 415.48. PubChem CID: 68299673. Isomeric SMILES: CCN1C(=O)COC2=C1C=C(C(=N2)C3=CC=C(C=C3)C4(CC(C4)O)N)C5=CC=CC=C5.