Encequidar mesylate | CAS#849675-87-2 | P-gp inhibitor

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

MedKoo CAT#: 401510

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.

Chemical Structure

Encequidar mesylate

CAS# 849675-87-2 (mesylate)

Product data Instruction

Theoretical Analysis

MedKoo Cat#: 401510
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

Price and Availability

Size	Price	Availability
5mg	USD 150	Ready to ship
10mg	USD 250	Ready to ship
25mg	USD 450	Ready to ship
50mg	USD 750	Ready to ship
100mg	USD 1350	Ready to ship
200mg	USD 2350	Ready to ship
Bulk inquiry Welcome, Customer: Please do not inquire quote if your intended use is for a patient since our products are for research use and for chemical synthesis use, not for human use . For in-stock products, we listed price in the web page. You may inquire prices for which sizes were not listed. If no price is listed, this means the product is not in stock at the moment, which may be available via custom synthesis. For cost-effective reason, minimum order of 1g is requested (typically very expensive). The lead time is usually 2-4 months. Quote of less than 1g will not be provided. MedKoo may not offer quote for below reasons: (1) current available synthetic method appears to be extremely expensive which is obviously not affordable to most customers; (2) Key raw material to make the product is temporally not available; (3) DEA controlled substances; (4) the product is under patent protection in customer’s country.

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)

Product Data:

Product Data

Certificate of Analysis:

View CoA: current batch, Lot#A22T05K24

QC Data:

View QC data: current batch, Lot#A22T05K24

Safety Data Sheet (SDS):

View Safety Data Sheet (SDS)

Instruction:

View handling instruction

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/

Solubility Data

	Solvent	Max Conc. mg/mL	Max Conc. mM
Solubility
	DMSO	25.0	31.85

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.

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.

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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.

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