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MedKoo Cat#: 401510 | Name: Encequidar mesylate
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Description:

WARNING: This product is for research use only, not for human or veterinary use.

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.

Chemical Structure

Encequidar mesylate
Encequidar mesylate
CAS#849675-87-2 (mesylate)

Theoretical Analysis

MedKoo Cat#: 401510

Name: Encequidar mesylate

CAS#: 849675-87-2 (mesylate)

Chemical Formula: C39H40N6O10S

Exact Mass: 0.0000

Molecular Weight: 784.84

Elemental Analysis: C, 59.68; H, 5.14; N, 10.71; O, 20.39; S, 4.08

Price and Availability

Size Price Availability Quantity
5mg USD 150.00 Ready to ship
10mg USD 250.00 Ready to ship
25mg USD 450.00 Ready to ship
50mg USD 750.00 Ready to ship
100mg USD 1,350.00 Ready to ship
200mg USD 2,350.00 Ready to ship
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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 mg/mL mM
Solubility
DMSO 25.0 31.85
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

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.

Recalculate based on batch purity %
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: 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: Zhang H, Bian S, Xu Z, Gao M, Wang H, Zhang J, Zhang M, Ke Y, Wang W, Chen ZS, Xu H. The effect and mechanistic study of encequidar on reversing the resistance of SW620/AD300 cells to doxorubicin. Biochem Pharmacol. 2022 Nov;205:115258. doi: 10.1016/j.bcp.2022.115258. Epub 2022 Sep 27. PMID: 36179932. 3: Jackson CGCA, Hung T, Segelov E, Barlow P, Prenen H, McLaren B, Hung NA, Clarke K, Chao TY, Dai MS, Yeh HT, Cutler DL, Kramer D, He J, Zhi J, Chan WK, Kwan R, Deva S. Oral paclitaxel with encequidar compared to intravenous paclitaxel in patients with advanced cancer: A randomised crossover pharmacokinetic study. Br J Clin Pharmacol. 2021 Dec;87(12):4670-4680. doi: 10.1111/bcp.14886. Epub 2021 Jun 18. PMID: 33960504. 4: Dai MS, Chao TC, Chiu CF, Lu YS, Shiah HS, Jackson CGCA, Hung N, Zhi J, Cutler DL, Kwan R, Kramer D, Chan WK, Qin A, Tseng KC, Hung CT, Chao TY. Oral paclitaxel and encequidar in patients with breast cancer: a pharmacokinetic, safety, and antitumor activity study. Ther Adv Med Oncol. 2023 Jul 21;15:17588359231183680. doi: 10.1177/17588359231183680. PMID: 37492633; PMCID: PMC10363869. 5: Chu J, Panfen E, Wang L, Marino A, Chen XQ, Fancher RM, Landage R, Patil O, Desai SD, Shah D, Xue Y, Sinz M, Shen H. Evaluation of Encequidar as An Intestinal P-gp and BCRP Specific Inhibitor to Assess the Role of Intestinal P-gp and BCRP in Drug-Drug Interactions. Pharm Res. 2023 Jul 31. doi: 10.1007/s11095-023-03563-4. Epub ahead of print. PMID: 37523014. 6: Ma WW, Li JJ, Azad NS, Lam ET, Diamond JR, Dy GK, Opyrchal M, Zhi J, Kramer D, Chan WK, Cutler D, Kwan R, Adjei AA, Jimeno A. A phase Ib study of Oraxol (oral paclitaxel and encequidar) in patients with advanced malignancies. Cancer Chemother Pharmacol. 2022 Jul;90(1):7-17. doi: 10.1007/s00280-022-04443-1. Epub 2022 Jun 22. PMID: 35731258. 7: Sharma D, Wojtynek J, Fox KM, Cooper C, Dokubo I. Cost of home vs clinic administration of paclitaxel in metastatic breast cancer. Am J Manag Care. 2021 Feb;27(2 Spec. No.):SP46-SP50. doi: 10.37765/ajmc.2021.88563. Epub 2020 Dec 24. PMID: 33395244. 8: McCaw ZR, Ludmir EB, Wei LJ. Assessing the Clinical Utility of Oral Paclitaxel Plus Encequidar Versus Intravenous Paclitaxel in Patients With Metastatic Breast Cancer. J Clin Oncol. 2023 Feb 20;41(6):1323. doi: 10.1200/JCO.22.01759. Epub 2022 Nov 3. PMID: 36331242. 9: Rugo HS, Umanzor GA, Barrios FJ, Vasallo RH, Chivalan MA, Bejarano S, Ramírez JR, Fein L, Kowalyszyn RD, Kramer ED, Wang H, Kwan MR, Cutler DL; Oraxol Study Consortium Investigators. Open-Label, Randomized, Multicenter, Phase III Study Comparing Oral Paclitaxel Plus Encequidar Versus Intravenous Paclitaxel in Patients With Metastatic Breast Cancer. J Clin Oncol. 2023 Jan 1;41(1):65-74. doi: 10.1200/JCO.21.02953. Epub 2022 Jul 20. PMID: 35858154; PMCID: PMC9788977. 10: Urgaonkar S, Nosol K, Said AM, Nasief NN, Bu Y, Locher KP, Lau JYN, Smolinski MP. Discovery and Characterization of Potent Dual P-Glycoprotein and CYP3A4 Inhibitors: Design, Synthesis, Cryo-EM Analysis, and Biological Evaluations. J Med Chem. 2022 Jan 13;65(1):191-216. doi: 10.1021/acs.jmedchem.1c01272. Epub 2021 Dec 20. PMID: 34928144. 11: Boland PM, Fountzilas C, Fakih M, Opyrchal M, Diamond JR, Corr B, Ma WW, Redman M, Chan WK, Wang H, Kramer D, Kwan R, Cutler D, Zhi J, Jimeno A. A dose regimen-finding study to evaluate the safety, tolerability, pharmacokinetics, and activity of oratecan in subjects with advanced malignancies. Cancer Chemother Pharmacol. 2022 Aug;90(2):175-187. doi: 10.1007/s00280-022-04453-z. Epub 2022 Jul 29. PMID: 35904620. 12: He J, Jackson CGCA, Deva S, Hung T, Clarke K, Segelov E, Chao TY, Dai MS, Yeh HT, Ma WW, Kramer D, Chan WK, Kwan R, Cutler D, Zhi J. Population pharmacokinetics for oral paclitaxel in patients with advanced/metastatic solid tumors. CPT Pharmacometrics Syst Pharmacol. 2022 Jul;11(7):867-879. doi: 10.1002/psp4.12799. Epub 2022 May 10. PMID: 35470967; PMCID: PMC9286714. 13: Keefer C, Chang G, Carlo A, Novak JJ, Banker M, Carey J, Cianfrogna J, Eng H, Jagla C, Johnson N, Jones R, Jordan S, Lazzaro S, Liu J, Scott Obach R, Riccardi K, Tess D, Umland J, Racich J, Varma M, Visswanathan R, Di L. Mechanistic insights on clearance and inhibition discordance between liver microsomes and hepatocytes when clearance in liver microsomes is higher than in hepatocytes. Eur J Pharm Sci. 2020 Dec 1;155:105541. doi: 10.1016/j.ejps.2020.105541. Epub 2020 Sep 12. PMID: 32927071.