| Size | Price | Stock | Qty |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| Other Sizes |
| Targets |
Rimegepant sulfate hydrate targets the calcitonin gene-related peptide (CGRP) receptor (also known as CLR/RAMP1 complex). It acts as a competitive antagonist. In a human SK-N-MC cell membrane binding assay using [¹²⁵I]-CGRP, rimegepant exhibits a Ki (inhibition constant) of approximately 0.027 nM (27 pM) for the human CGRP receptor. It shows high selectivity (>10,000-fold) against other related receptors including adrenomedullin (AM1, AM2), calcitonin, and amylin receptors.
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| ln Vitro |
In a functional antagonism assay using SK-N-MC cells endogenously expressing human CGRP receptors, rimegepant potently inhibits CGRP-induced cAMP accumulation with an IC50 of approximately 0.3 nM. It shows no significant agonist activity up to 10 µM. Rimegepant does not inhibit a panel of 70 other receptors, ion channels, and enzymes at concentrations up to 10 µM, demonstrating excellent selectivity. In isolated human cerebral and coronary arteries, rimegepant does not produce vasoconstriction nor does it reverse CGRP-mediated relaxation, indicating a clean vascular safety profile compared to triptans.
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| ln Vivo |
In a rat pharmacodynamic model, oral administration of rimegepant (3–30 mg/kg) dose-dependently inhibits CGRP-induced increase in dermal blood flow (measured by laser Doppler), with an ED50 of approximately 14 mg/kg. In a marmoset facial blood flow model, rimegepant (0.3–3 mg/kg, p.o.) inhibits capsaicin-induced facial flushing (a CGRP-mediated response) with an ED50 of about 0.6 mg/kg. In a cynomolgus monkey model of trigeminal nerve stimulation, rimegepant (0.1–1 mg/kg, i.v.) dose-dependently reduces facial blood flow increases, confirming target engagement. These models demonstrate that rimegepant effectively blocks CGRP-mediated effects in vivo at clinically relevant exposures.
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| Enzyme Assay |
Human CGRP receptor binding affinity of rimegepant was determined using a radioligand binding assay. Membranes prepared from SK-N-MC cells (endogenously expressing human CGRP receptors) were incubated with 0.03 nM [¹²⁵I]-CGRP (human) and increasing concentrations of rimegepant in assay buffer (50 mM HEPES, pH 7.4, 5 mM MgCl₂, 0.1% BSA) for 90–120 minutes at room temperature. Non-specific binding was defined using 1 µM unlabeled CGRP. Bound and free radioactivity were separated by rapid filtration through GF/B filters presoaked in 0.3% polyethyleneimine using a cell harvester. Filters were washed, and retained radioactivity was counted in a gamma counter. Ki values were calculated via nonlinear regression using the Cheng-Prusoff equation. [1]
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| Cell Assay |
Functional antagonism of rimegepant at the human CGRP receptor was assessed using a cAMP accumulation assay (HTRF or AlphaScreen format). SK-N-MC cells (50,000–100,000 cells/well) were seeded in 96-well plates and incubated with increasing concentrations of rimegepant (0.001–10,000 nM) for 30 minutes at 37°C, followed by stimulation with 0.3 nM human CGRP (approximately EC80) for 30 minutes. The reaction was terminated by lysis buffer, and intracellular cAMP levels were quantified using a homogeneous time-resolved fluorescence (HTRF) cAMP kit or AlphaScreen assay. The EC50 for CGRP was determined in each experiment, and rimegepant’s inhibitory IC50 was calculated using a four-parameter logistic equation. The IC50 for rimegepant was approximately 0.3 nM. [1]
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| Animal Protocol |
In a rat pharmacodynamic model, male Sprague-Dawley rats were anesthetized and the dorsal skin was shaved. A laser Doppler probe was placed to measure basal blood flow. CGRP (0.3 µg/kg, i.v.) was administered to induce an increase in blood flow. Rimegepant was suspended in 0.5% methylcellulose and administered orally (p.o.) at doses of 3, 10, and 30 mg/kg (5 mL/kg) 60 minutes prior to CGRP challenge. The CGRP-induced peak blood flow increase (typically occurring 2–5 minutes post-CGRP) was recorded and expressed as percentage of baseline. Vehicle control was used for comparison. The ED50 was calculated as approximately 14 mg/kg. [1]
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| ADME/Pharmacokinetics |
In preclinical species, rimegepant shows moderate clearance and high oral bioavailability. In rats (1 mg/kg, i.v.; 5 mg/kg, p.o.), the terminal half-life (t½) is approximately 4–6 hours, oral bioavailability is 45–60%, and volume of distribution (Vdss) is 3–5 L/kg. In cynomolgus monkeys (1 mg/kg, i.v.; 5 mg/kg, p.o.), t½ is 10–15 hours, oral bioavailability is 20–35%, and Vdss is ~2 L/kg. Plasma protein binding in humans is approximately 96–98%, primarily to albumin. In healthy human subjects, after a single oral dose of 75 mg (ODT), the median Tmax is 1.5 hours, mean Cmax is approximately 210–250 ng/mL, and the mean AUC0-∞ is approximately 1200–1500 ng·h/mL. The terminal t½ is ~11 hours, supporting once-daily dosing. Rimegepant is primarily metabolized by CYP3A4 and to a lesser extent by CYP2C9, with renal excretion as the major elimination pathway (approx. 50% unchanged in urine).
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| Toxicity/Toxicokinetics |
In preclinical toxicology studies, rimegepant was well tolerated up to high doses. In 28-day repeat-dose toxicity studies in rats and cynomolgus monkeys, the no-observed-adverse-effect-level (NOAEL) was 100 mg/kg/day (approximately 400-fold the human AUC at the clinical dose). No genotoxicity was observed in the Ames test, in vitro chromosome aberration assay, or in vivo rat micronucleus test. No reproductive toxicity was noted in rat fertility or embryofetal development studies up to 100 mg/kg/day. In a 2-year rat carcinogenicity study, no treatment-related tumors were observed. At supra-therapeutic doses, mild hepatocyte hypertrophy (due to CYP3A induction) was observed, which is reversible and not considered clinically relevant. In human clinical trials, the most common adverse events with rimegepant (≥1% and ≥ placebo) were nausea (1.9–2.7%) and hypersensitivity reactions (<1%).
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| References | |
| Additional Infomation |
Rimegepant is approved in the US, EU, and other regions as Nurtec® ODT (orally disintegrating tablet) for acute treatment of migraine with or without aura and for preventive treatment of episodic migraine. The recommended dose is 75 mg once daily as needed for acute treatment, or every other day for prevention. Unlike triptans, rimegepant does not cause vasoconstriction and therefore is not contraindicated in patients with cardiovascular disease. It is a substrate of CYP3A4 and P-gp, thus concomitant use with strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin) or inducers (e.g., rifampin, carbamazepine) may affect exposure. Rimegepant should not be used concurrently with another CGRP receptor antagonist (e.g., ubrogepant, atogepant) or with CGRP monoclonal antibodies. Pregnancy category: no adequate human data; animal studies showed no risk.
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| Molecular Formula |
C28H32F2N6O3.1/2H2O4S.3/2H2O
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| Molecular Weight |
610.26
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| Exact Mass |
1220.437
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| Elemental Analysis |
C, 55.08; H, 5.28; F, 6.22; N, 13.76; O, 17.03; S, 2.63
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| CAS # |
1374024-48-2
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| Related CAS # |
Rimegepant;1289023-67-1;Rimegepant hemisulfate (BMS927711 hemisulfate); 1642783-82-1
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| PubChem CID |
71586738
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| Appearance |
Typically exists as solids at room temperature
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| Hydrogen Bond Donor Count |
9
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| Hydrogen Bond Acceptor Count |
23
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
86
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| Complexity |
973
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| Defined Atom Stereocenter Count |
6
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| SMILES |
S(=O)(=O)(O)O.FC1C(=CC=CC=1[C@H]1[C@@H](C2=CC=CN=C2[C@@H](CC1)OC(N1CCC(CC1)N1C(NC2C1=CC=CN=2)=O)=O)N)F.FC1C(=CC=CC=1[C@H]1[C@@H](C2=CC=CN=C2[C@@H](CC1)OC(N1CCC(CC1)N1C(NC2C1=CC=CN=2)=O)=O)N)F.O.O.O
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| InChi Key |
SOGUOEZRYKUOHR-CQZKMDJHSA-N
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| InChi Code |
InChI=1S/2C28H28F2N6O3.H2O4S.3H2O/c2*29-20-6-1-4-17(23(20)30)18-8-9-22(25-19(24(18)31)5-2-12-32-25)39-28(38)35-14-10-16(11-15-35)36-21-7-3-13-33-26(21)34-27(36)37;1-5(2,3)4;;;/h2*1-7,12-13,16,18,22,24H,8-11,14-15,31H2,(H,33,34,37);(H2,1,2,3,4);3*1H2/t2*18-,22+,24-;;;;/m00..../s1
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| Chemical Name |
bis([(5S,6S,9R)-5-amino-6-(2,3-difluorophenyl)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-9-yl] 4-(2-oxo-3H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxylate);sulfuric acid;trihydrate
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| Synonyms |
BMS-927711 sulfate hydrate; Rimegepant sulfate; 1374024-48-2; Nurtec ODT; 1383NM3Q0H; DTXSID60160174; BHV-3000 sulfate hydrate
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| HS Tariff Code |
2934.99.9001
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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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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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 | 1.6386 mL | 8.1932 mL | 16.3865 mL | |
| 5 mM | 0.3277 mL | 1.6386 mL | 3.2773 mL | |
| 10 mM | 0.1639 mL | 0.8193 mL | 1.6386 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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