Encequidar mesylate (HM30181 (mesylate)) (Synonyms: HM30181 mesylate; HM30181A mesylate)

HM30181 mesylate salt, a tetrazole derivative, is known as a P-glycoprotein inhibitor that has inhibitory activities on multidrug resistance in cancer cells[1,5]. HM30181 has a strong inhibitory effect on MDR1-mediated paclitaxel transport in membrane vesicles. The IC50 value of HM30181 is 0.63 nM[2].

HM30181(10-10M-10-4M;5 min; 37℃) is an effective inhibitor of MDR1in 293FRT-MDR1 cells[2]. The survival inhibition rates of 0.1 nM and 1 nM Encequidar (HM30181) were 20% and 42% respectively, at 100 nM and 1000 nM NSC 125973[3].

HM30181 can significantly improve the bioavailability of oral paclitaxel. In the xenograft model in nude mice, oral co-administration of paclitaxel and HM30181 effectively inhibited tumor growth [2,4].

References:
[1]. Bauer F, Wanek T, 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. doi: 10.1016/j.ejphar.2012.09.013. Epub 2012 Sep 26. PMID: 23022332; PMCID: PMC3690544.
[2]. J.O. Kwak, S.H. Lee, et,al. Selective inhibition of MDR1 (ABCB1) by HM30181 increases oral bioavailability and therapeutic efficacy of paclitaxel
[3]. Joo KM, Song SY, et,al.Response of brain specific microenvironment to P-glycoprotein inhibitor: an important factor determining therapeutic effect of P-glycoprotein inhibitor on brain metastatic tumors. Int J Oncol. 2008 Oct;33(4):705-12. PMID: 18813783.
[4]. Kim JC, Kim KS, et,al. Effect of HM30181 mesylate salt-loaded microcapsules on the oral absorption of paclitaxel as a novel P-glycoprotein inhibitor. Int J Pharm. 2016 Jun 15;506(1-2):93-101. doi: 10.1016/j.ijpharm.2016.04.034. Epub 2016 Apr 19. PMID: 27106527.
[5]. J.O. Lee, Y.S. Youn, et,al. Development of poly(lactic-co-glycolic acid) microparticles with pH-sensitive drug release behaviors. J. Pharm. Invest., 45 (2) (2015), pp. 151-156