| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| Other Sizes |
|
Vibegron (also known as KRP-114V; MK-4618; trade name Gemtesa) is a novel and potent β3 adrenergic receptor agonist approved in 2020 for the treatment of overactive bladder, which is a condition in which the bladder muscles contract uncontrollably and cause frequent urination.
| ln Vivo |
A dose-dependent reduction in micturition pressure and an increase in functional bladder capacity are observed with vitegron (1~12 μM; iv) [3]. Vibegron (30 mg/kg; oral; 4 weeks) increases the levels of TGF-β1, HIF-1α, and collagen type 1 and type 3 mRNA [4]. When compared to oxo-M untreated rats (intravesical instillation of vehicle), bebegron (1 and 10 mg/kg; i.v.; 30 min apart) significantly reduces bladder capacity in oxo-M treated rats [5].
|
|---|---|
| Animal Protocol |
Animal/Disease Models: Rat
Doses: 1~12 μM Route of Administration: intravenous (iv) (iv)injection Experimental Results: Demonstrated dose-dependent decrease in micturition pressure and increase in functional bladder capacity. Animal/Disease Models: Female C57BL/6N mice (9 weeks old) Doses: 30 mg/kg Route of Administration: Po; 4-week Experimental Results: mRNA levels of type 1, type 3 collagen, TGF-β1 and HIF-1α at 4 weeks Upregulated. Animal/Disease Models: Female F344 rats (120–160 g) Doses: 1 and 10 mg/kg Route of Administration: intravenously (iv) (iv)(iv); 30 min intervals Experimental Results: vs. oxo-M untreated rats (intravesical instillation of vehicle) In comparison, Vibegron (10 mg/kg) Dramatically diminished bladder capacity in oxo-M-treated rats. |
| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion
The mean Tmax is 1-3 hours. Steady-state concentrations are achieved within 7 days of once-daily dosing. In a radiolabeled drug study, approximately 59% of the radiolabeled dose was recovered in feces, in which 54% of that amount was in the unchanged parent drug form. About 20% of the radioactivity was recovered in urine, in which 19% of the amount was in the unchanged form. The mean apparent volume of distribution is 6304 L. The average blood-to-plasma concentration ratio is 0.9. According to tissue distribution studies in animals, vibegron does not penetrate the blood-brain barrier, suggesting limited potential for CNS toxicity in humans. There is limited information on the clearance rate of vibegron. Metabolism / Metabolites In vitro, CYP3A4 is the main enzyme responsible for the metabolism of vibegron, which plays a minor role in the elimination of vibegron. Two predominant metabolic pathways are oxidation and glucuronidation to form two oxidative metabolites and three glucuronide metabolites. Metabolites have not been fully characterized. Biological Half-Life The terminal plasma half-life ranges from 60 to 70 hours. The effective half-life is 30.8 hours. |
| Toxicity/Toxicokinetics |
Hepatotoxicity
Vibegron, like other beta-adrenergic agents, is rarely associated with serum ALT or alkaline phosphatase elevations. In large randomized, placebo-controlled trials, serum aminotransferase elevations arose in less than 1% of treated participants, rates that were similar to patients receiving placebo and comparator agents such as tolterodine. In the registration trials of vibegron and since its approval and more widescale use, there have been no reports of clinically apparent liver injury. Likelihood score: E (unlikely cause of clinically apparent liver injury). Protein Binding Vibegron is 49.6–51.3% bound to human plasma proteins. |
| References |
|
| Additional Infomation |
Pharmacodynamics
Vibegron selectivity for beta-3 adrenergic receptors is >9000 times higher than for β1AR or β2AR. Vibegron improves clinical symptoms of overactive bladder by increasing bladder capacity without affecting bladder contraction. It significantly increases the functional bladder volume in a dose-dependent manner, which results in prolongation of the interval between voids. In clinical studies, vibegron inhibited detrusor bladder contractions in a concentration-dependent manner, reduced voiding pressure, and increased bladder compliance. In Japanese clinical studies comprising patients with overactive bladder, vibegron significantly improved the frequency of micturition, urgency, and urgency incontinence episodes. |
| Molecular Formula |
C26H28N4O3
|
|---|---|
| Molecular Weight |
444.535
|
| Exact Mass |
444.216
|
| CAS # |
1190389-15-1
|
| PubChem CID |
44472635
|
| Appearance |
White to off-white solid powder
|
| Density |
1.4±0.1 g/cm3
|
| Index of Refraction |
1.698
|
| LogP |
0.66
|
| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
5
|
| Rotatable Bond Count |
6
|
| Heavy Atom Count |
33
|
| Complexity |
782
|
| Defined Atom Stereocenter Count |
4
|
| SMILES |
C1C[C@@H](N[C@@H]1CC2=CC=C(C=C2)NC(=O)[C@@H]3CCC4=NC=CC(=O)N34)[C@@H](C5=CC=CC=C5)O
|
| InChi Key |
DJXRIQMCROIRCZ-XOEOCAAJSA-N
|
| InChi Code |
InChI=1S/C26H28N4O3/c31-24-14-15-27-23-13-12-22(30(23)24)26(33)29-19-8-6-17(7-9-19)16-20-10-11-21(28-20)25(32)18-4-2-1-3-5-18/h1-9,14-15,20-22,25,28,32H,10-13,16H2,(H,29,33)/t20-,21+,22-,25+/m0/s1
|
| Chemical Name |
(6S)-N-[4-[[(2S,5R)-5-[(R)-hydroxy(phenyl)methyl]pyrrolidin-2-yl]methyl]phenyl]-4-oxo-7,8-dihydro-6H-pyrrolo[1,2-a]pyrimidine-6-carboxamide
|
| Synonyms |
MK4618KRP114VMK 4618 VIBEGRON KRP-114VUNII-M5TSE03W5U MK-4618 KRP 114V
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO : ~95 mg/mL (~213.71 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 4.75 mg/mL (10.69 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 47.5 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 4.75 mg/mL (10.69 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 47.5 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 4.75 mg/mL (10.69 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2495 mL | 11.2476 mL | 22.4952 mL | |
| 5 mM | 0.4499 mL | 2.2495 mL | 4.4990 mL | |
| 10 mM | 0.2250 mL | 1.1248 mL | 2.2495 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
