Perhexiline is an orally active inhibitor of CPT1 and CPT2 that reduces fatty acid metabolism. Perhexiline can cross the blood-brain barrier (BBB) and exhibits anti-tumor activity. Perhexiline induces mitochondrial dysfunction and apoptosis in hepatocytes. Therefore, Perhexiline can be used in cancer and cardiovascular disease research [1] [2] [5].

Perhexiline (5-25 μM, 2-6 h) reduces cell viability in HepG2 cells [2]. Perhexiline (5-25 μM, 2-6 h) reduces cellular ATP content and Lactate dehydrogenase (LDH) release in HepG2 cells [2]. Perhexiline (20 μM, 2 h) activates caspase 3/7 in HepG2 cells [2]. Perhexiline (5-25 μM, 4 h) causes mitochondrial dysfunction in HepG2 cells [2]. Perhexiline (5 μM, 48 h) selectively induces massive apoptosis in CLL cells (high expression of CPT) [3]. Cell Viability Assay [2] Cell Line: HepG2 cells Concentration: 5, 10, 15, 25 μM Incubation Time: 2, 4, 6 h Result: Induced time- and concentration-dependent cytotoxicity in hepatic cells. Western Blot Analysis [2] Cell Line: HepG2 cells Concentration: 5, 10, 15, 25 μM Incubation Time: 2 h Result: Reduced Bcl-2 and Mcl-1 level, and increased Bad level.

Perhexiline (200 mg/kg, p.o., daily for 8 weeks) reduces peripheral neural function in female DA rats [4]. Perhexiline (80 mg/kg, oral gavage, for 3 days) demonstrates anti-tumor activity in glioblastoma mouse model [5]. Animal Model: Orthotopic glioblastoma mouse model [5] Dosage: 80 mg/kg Administration: Oral gavage, for 3 days. Result: Reduces tumor size (MR imaging) and improves in overall survival.