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Purity: ≥98%
Encequidar (formerly HM-30181; HM30181; HM30181A) is a novel, potent, selective, and orally bioavailable inhibitor of the adenosine triphosphate (ATP)-binding cassette (ABC) transporter P-gp (P-glycoprotein). It was designed to improve the oral bioavailability of drugs that are P-gp substrates which may otherwise be pumped out of cells by P-gp, leading to drug resistance. Encequidar was supported by FDA in March 2021 for the new drug application for combination with oral paclitaxel in the treatment of patients with metastatic breast cancer. Oral paclitaxel and encequidar is the first world taxane to demonstrate superiority in radiologically confirmed tumor response rate, with reduced neuropathy and alopecia compared to IV paclitaxel in women with metastatic breast cancer. 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.
| ln Vitro |
When it comes to preventing rhodamine 123 efflux from CCRF-CEM T cells, encequidar (HM30181; HM30181A) is about equal to the standard Pgp inhibitor tariquidar (IC50, tariquidar: 8.2±2.0 nM, encequidar (HM30181): 13.1±2.3 nM) [1]. Compared to tariquitar, another third-generation P-gp inhibitor, encequidar (HM30181) is 20–50 times more powerful and shows strong selectivity for mP-gp [2].
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| ln Vivo |
Pgp substrate (R)-based PET scans [11C]NSC 657799 did not demonstrate (R)- [11C].When NSC was applied to mice treated with a vehicle, brain uptake was dramatically boosted by 657799 [1]. P-gp is mostly inhibited in intestinal endothelium cells by encequidar (HM30181), which may be advantageous because P-gp inhibition across the board, especially in the brain, may result in harmful side effects. In rats, encequidar (HM30181) enhanced co-administered NSC 125973's oral bioavailability by a factor of more than 12 [2].
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| References |
[1]. Bauer F, 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.
[2]. Kim TE, et al. Effects of HM30181, a P-glycoprotein inhibitor, on the pharmacokinetics and pharmacodynamics of loperamide in healthy volunteers. Br J Clin Pharmacol. 2014 Sep;78(3):556-64 |
| Molecular Formula |
C38H36N6O7
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|---|---|
| Molecular Weight |
688.7284
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| CAS # |
849675-66-7
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| Related CAS # |
Encequidar mesylate;849675-87-2;Encequidar mesylate hydrochloride;2097125-58-9
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| SMILES |
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
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| InChi Key |
AHJUHHDDCJQACA-UHFFFAOYSA-N
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| 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)
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| 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
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| Synonyms |
HM30181A HM30181 HM-30181A HM-30181 HM 30181A HM-30181 free base HM 30181.
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~2.4 mg/mL (~3.48 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.4519 mL | 7.2597 mL | 14.5195 mL | |
| 5 mM | 0.2904 mL | 1.4519 mL | 2.9039 mL | |
| 10 mM | 0.1452 mL | 0.7260 mL | 1.4519 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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