WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H401510
CAS#: 849675-87-2 (mesylate)
Description: Encequidar, also known as HM-30181, is an oral P-glycoprotein (P-gp) inhibitor developed to enhance the oral bioavailability of P-gp substrate drugs. Encequidar showed the highest potency (IC(50)=0.63nM) among several MDR1 inhibitors, including cycloporin A, XR9576, and GF120918, and effectively blocked transepithelial transport of paclitaxel in MDCK monolayers (IC(50)=35.4nM). Encequidar is currently under clinical trials.
Hodoodo Cat#: H401510
Name: Encequidar mesylate
CAS#: 849675-87-2 (mesylate)
Chemical Formula: C39H40N6O10S
Exact Mass: 0.00
Molecular Weight: 784.841
Elemental Analysis: C, 59.68; H, 5.14; N, 10.71; O, 20.39; S, 4.08
Related CAS #: 849675-66-7 (free base) 849675-87-2 (mesylate) 849675-88-3 (HCl)
Synonym: HM30181; HM-30181; HM 30181; HM-30181 mesylate; Encequidar mesylate
IUPAC/Chemical Name: N-(2-(2-(4-(2-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)ethyl)phenyl)-2H-tetrazol-5-yl)-4,5-dimethoxyphenyl)-4-oxo-4H-chromene-2-carboxamide methanesulfonate
InChi Key: PEKXWELLWNPUOK-UHFFFAOYSA-N
InChi Code: InChI=1S/C38H36N6O7.CH4O3S/c1-47-32-17-24-14-16-43(22-25(24)18-33(32)48-2)15-13-23-9-11-26(12-10-23)44-41-37(40-42-44)28-19-34(49-3)35(50-4)20-29(28)39-38(46)36-21-30(45)27-7-5-6-8-31(27)51-36;1-5(2,3)4/h5-12,17-21H,13-16,22H2,1-4H3,(H,39,46);1H3,(H,2,3,4)
SMILES Code: O=C(NC1=CC(OC)=C(C=C1C2=NN(N=N2)C3=CC=C(C=C3)CCN4CC5=C(CC4)C=C(C(OC)=C5)OC)OC)C6=CC(C7=C(C=CC=C7)O6)=O.OS(=O)(C)=O
Appearance: white solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
More Info: Related CAS# 49675-66-7 (HM30181 Free base); 849675-87-2 (HM30181 mesylate salt); 849675-88-3 (HM30181 HCl salt)
| Biological target: | Encequidar mesylate (HM30181 mesylate; HM30181A mesylate) is a competitive and potent P-glycoprotein inhibitor. |
| In vitro activity: | Based on these data, the IC50 of encequidar for inhibition of P-gp in Caco-2 intestinal cells was determined to be 53 nM, demonstrating that encequidar potently inhibits P-gp and prevents the efflux of paclitaxel from intestinal cells in vitro. Reference: J Med Chem. 2021 Apr 8;64(7):3677-3693. https://pubmed.ncbi.nlm.nih.gov/33729781/ |
| In vivo activity: | 40 mg/kg paclitaxel (in combination with 20 mg/kg encequidar) suppressed tumor growth by 94% and induced remission of tumor growth until day 47, an outcome superior to the IV paclitaxel arm included in the study. The results of this study demonstrate the ability of encequidar to inhibit P-gp and facilitate the absorption of paclitaxel to therapeutically effective plasma concentrations in vivo. Clinically, paclitaxel is used to treat many different types of cancers, including breast, lung, and ovarian cancer. Reference: J Med Chem. 2021 Apr 8;64(7):3677-3693. https://pubmed.ncbi.nlm.nih.gov/33729781/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 25.0 | 31.85 |
The following data is based on the product molecular weight 784.84 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | 1. Smolinski MP, Urgaonkar S, Pitzonka L, Cutler M, Lee G, Suh KH, Lau JYN. Discovery of Encequidar, First-in-Class Intestine Specific P-glycoprotein Inhibitor. J Med Chem. 2021 Apr 8;64(7):3677-3693. doi: 10.1021/acs.jmedchem.0c01826. Epub 2021 Mar 17. PMID: 33729781. 2. Joo KM, Song SY, Park K, Kim MH, Jin J, Kang BG, Jang MJ, Lee GS, Kim MS, Nam DH. 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. |
| In vitro protocol: | 1. Smolinski MP, Urgaonkar S, Pitzonka L, Cutler M, Lee G, Suh KH, Lau JYN. Discovery of Encequidar, First-in-Class Intestine Specific P-glycoprotein Inhibitor. J Med Chem. 2021 Apr 8;64(7):3677-3693. doi: 10.1021/acs.jmedchem.0c01826. Epub 2021 Mar 17. PMID: 33729781. 2. Joo KM, Song SY, Park K, Kim MH, Jin J, Kang BG, Jang MJ, Lee GS, Kim MS, Nam DH. 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. |
| In vivo protocol: | 1. Smolinski MP, Urgaonkar S, Pitzonka L, Cutler M, Lee G, Suh KH, Lau JYN. Discovery of Encequidar, First-in-Class Intestine Specific P-glycoprotein Inhibitor. J Med Chem. 2021 Apr 8;64(7):3677-3693. doi: 10.1021/acs.jmedchem.0c01826. Epub 2021 Mar 17. PMID: 33729781. 2. Joo KM, Song SY, Park K, Kim MH, Jin J, Kang BG, Jang MJ, Lee GS, Kim MS, Nam DH. 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. |
1: Cha YJ, Lee H, Gu N, Kim TE, Lim KS, Yoon SH, Chung JY, Jang IJ, Shin SG, Yu KS, Cho JY. Sustained Increase in the Oral Bioavailability of Loperamide after a Single Oral Dose of HM30181, a P-glycoprotein Inhibitor, in Healthy Male Participants. Basic Clin Pharmacol Toxicol. 2013 Jul 6. doi: 10.1111/bcpt.12108. [Epub ahead of print] PubMed PMID: 23829508.
2: Bauer F, Wanek T, Mairinger S, Stanek J, Sauberer M, Kuntner C, Parveen Z, Chiba P, Müller M, Langer O, Erker T. 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. PubMed PMID: 23022332; PubMed Central PMCID: PMC3690544.
3: Kim TE, Gu N, Yoon SH, Cho JY, Park KM, Shin SG, Jang IJ, Yu KS. Tolerability and pharmacokinetics of a new P-glycoprotein inhibitor, HM30181, in healthy Korean male volunteers: single- and multiple-dose randomized, placebo-controlled studies. Clin Ther. 2012 Feb;34(2):482-94. doi: 10.1016/j.clinthera.2012.01.003. Epub 2012 Jan 28. PubMed PMID: 22284902.
4: Kwak JO, Lee SH, Lee GS, Kim MS, Ahn YG, Lee JH, Kim SW, Kim KH, Lee MG. Selective inhibition of MDR1 (ABCB1) by HM30181 increases oral bioavailability and therapeutic efficacy of paclitaxel. Eur J Pharmacol. 2010 Feb 10;627(1-3):92-8. doi: 10.1016/j.ejphar.2009.11.008. Epub 2009 Nov 10. PubMed PMID: 19903471.
