HM30181

HM30181 is a potent and selective inhibitor of P-glycoprotein.

Signaling Pathways >> Membrane Transporter/Ion Channel >> P-glycoprotein

Research Areas >> Metabolic Disease

HM30181 is shown to be approximately equipotent with the reference Pgp inhibitor tariquidar in inhibiting rhodamine 123 efflux from CCRF-CEM T cells (IC50, tariquidar: 8.2±2.0 nM, HM30181: 13.1±2.3 nM) [1]. HM30181 shows a high selectivity for mP-gp and its potency is 20-50 times higher than that of tariquitar, another third generation P-gp inhibitor[2].

PET scans with the Pgp substrate (R)-[11C]verapamil in FVB wild-type mice pretreated i.v. with HM30181 (10 or 21 mg/kg) failes to show significant increases in (R)-[11C]verapamil brain uptake compared with vehicle treated animals[1]. HM30181 inhibits P-gp mainly in the intestinal endothelium, which can be beneficial because pan-inhibition of P-gp, particularly in the brain, could lead to detrimental adverse events. HM30181 increases the oral bioavailability of co-administered paclitaxel by more than 12 times in rats[2].

Mice: HM30181 mesylate is dissolved in 5% aqueous glucose solution, containing 20 μL 0.01 M aq. HCl and injected at a volume of 4 mL/kg. Female FVB wild-type mice, aged 8-12 weeks weighing 24±4 g undergo (R)-[11C]verapamil PET scans without and with i.v. pretreatment with cold HM30181. Animals are assigned to 5 groups (n=4 per group). One group is pretreated with HM30181 vehicle solution (5% aq. glucose solution containing 20 μL 0.01 M aq. HCl) at 60 min before start of the PET scan. The other groups are pretreated with either 10 mg/kg HM30181 at 10, 60 or 120 min before PET or with 21 mg/kg HM30181 at 10 min before PET[1].

[1]. Bauer F, et al. Interaction of HM30181 with P-glycoprotein at the murine blood-brain barrier assessed with positron emission tomography. Eur J Pharmacol. 2012 Dec 5;696(1-3):18-27.

[2]. Kim TE, et al. Effects of HM30181, a P-glycoprotein inhibitor, on the pharmacokinetics and pharmacodynamics of loperamide in healthy volunteers. Br J Clin Pharmacol. 2014 Sep;78(3):556-64.

elacridar | Valspodar | Tariquidar | Zosuquidar trihydrochloride | Risperidone | Sinapine thiocyanate | Piperine | (20S)-Protopanaxdiol | Dofequidar (fumarate) | NSC23925 | Alisol F | Polyoxyethylene stearate | Biricodar | HM30181 mesylate (Encequidar mesylate) | MCI826