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, at concentrations ranging from 5 to 25 μM and exposure periods between 2 to 6 hours, significantly decreases cell viability, ATP content, and lactate dehydrogenase (LDH) release, while also inducing mitochondrial dysfunction in HepG2 cells, as evidenced by studies [2]. Remarkably, a specific concentration of 20 μM for 2 hours activates caspase 3/7 in these cells, highlighting its potential pro-apoptotic effects [2]. Furthermore, at a lower concentration of 5 μM over a prolonged duration of 48 hours, perhexiline selectively triggers extensive apoptosis in CLL cells characterized by high CPT expression [3]. Assays performed, including cell viability and Western Blot analyses on HepG2 cells, demonstrated time- and concentration-dependent cytotoxicity alongside significant modulations in Bcl-2, Mcl-1, and Bad protein levels, underpinning the compound's impact on cellular survival pathways [2].

Perhexiline, administered at a dosage of 200 mg/kg orally once daily for 8 weeks, diminishes peripheral neural function in female DA rats [4]. At a lower dosage of 80 mg/kg given via oral gavage over three days, perhexiline exhibits anti-tumor properties in an orthotopic glioblastoma mouse model, leading to a reduction in tumor size (as assessed by MR imaging) and enhanced overall survival [5].