WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 206856
CAS#: 849675-66-7 (free base)
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.
MedKoo Cat#: 206856
Name: Encequidar free base
CAS#: 849675-66-7 (free base)
Chemical Formula: C38H36N6O7
Exact Mass: 688.2645
Molecular Weight: 688.741
Elemental Analysis: C, 66.27; H, 5.27; N, 12.20; O, 16.26
Synonym: Encequidar; HM-30181 free base; HM30181; HM-30181; HM 30181.
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
InChi Key: AHJUHHDDCJQACA-UHFFFAOYSA-N
InChi Code: InChI=1S/C38H36N6O7/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/h5-12,17-21H,13-16,22H2,1-4H3,(H,39,46)
SMILES Code: O=C(C1=CC(C2=C(O1)C=CC=C2)=O)NC3=CC(OC)=C(OC)C=C3C4=NN(C5=CC=C(CCN6CC7=C(C=C(OC)C(OC)=C7)CC6)C=C5)N=N4
Appearance: 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
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
|Biological target:||Encequidar (HM30181; HM30181A) is a potent and selective inhibitor of P-glycoprotein.|
|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. Therefore, we examined additional tumor models to broaden the therapeutic potential of oral paclitaxel when given in combination with oral encequidar. 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|
The following data is based on the product molecular weight 688.741 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.|
|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.|
|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.|
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, MÃ¼ller 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.