ASP4132

ASP4132 is an orally active, potent AMPK activator with an EC50 of 18 nM. ASP4132 has anti-cancer activity and makes tumor regression in breast cancer xenograft mouse models[1].

Signaling Pathways >> Epigenetics >> AMPK

Research Areas >> Cancer

Signaling Pathways >> PI3K/Akt/mTOR >> AMPK

AMPK:18 nM (EC50)

ASP4132 shows comparable cell growth inhibitory (IC50=0.014 μM) activity against MDA-MB-453 breast cancer cell[1]. ASP4132 shows relatively weak antiproliferative activity against SK-BR-3 (IC50>3 μM)[1].

ASP4132 (0.5-8 mg/kg; PO; once daily; for 21 days) causes the tumor growth inhibition and regression[1]. ASP4132 (1 mg/kg; IV or PO) has a T1/2 of 3.6 hours, a CLtot of 19 mL/min•kg, and a Vss of 4.6 L/kg for rats for IV[1]. ASP4132 is stable in human liver microsomes (HLM CLint, vitro=61 mL/min•kg)[1]. Animal Model: Five-week-old male nude mice with MDA-MB-453[1] Dosage: 0.5, 1, 2, 4, 8 mg/kg Administration: PO; once daily; for 21 days Result: The tumor growth inhibition (TGI) rate was 29% at 1 mg/kg, and the tumor regression rate was 26%, 87% and 96% at 2, 4 and 8 mg/kg, respectively. Animal Model: Male SD rats[1] Dosage: 1 mg/kg (Pharmacokinetic Analysis) Administration: IV or PO Result: Had a T1/2 of 3.6 hours, a CLtot of 19 mL/min•kg, and a Vss of 4.6 L/kg for rats for IV. Had a Cmax of 72 ng/mL and an AUC24h of 705 ng∙h/mL for PO.

[1]. Kazuyuki Kuramoto, et al. Development of a Potent and Orally Active Activator of Adenosine Monophosphate-Activated Protein Kinase (AMPK), ASP4132, as a Clinical Candidate for the Treatment of Human Cancer. Bioorg Med Chem. 2020 Mar 1;28(5):115307.