| Size | Price | Stock | Qty |
|---|---|---|---|
| 10mg |
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| Other Sizes |
| Targets |
BMS-986141 targets protease-activated receptor-4 (PAR-4), a G protein-coupled receptor that is activated by thrombin and plays a key role in platelet aggregation and thrombosis. By acting as a selective antagonist, BMS-986141 binds to PAR-4 and prevents its activation by thrombin. This inhibition blocks downstream signaling that leads to platelet aggregation, thereby exerting antithrombotic effects.
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| ln Vitro |
Compound 49, BMS-986141, has an IC50 value of 2.2 nM and inhibits platelet aggregation induced by PAR4 agonist peptide (0-1 μM) [1].
In vitro, BMS-986141 demonstrates potent antagonistic activity at PAR-4 with an IC50 of 0.4 nM. It inhibits PAR4-AP-induced platelet aggregation in human and monkey blood with IC50 values of 1.8 and 1.3 nM, respectively. At concentrations of 0-1 μM, BMS-986141 inhibits platelet aggregation induced by PAR4 agonist peptide. These data demonstrate its high potency as a PAR-4 antagonist. |
| ln Vivo |
BMS-986141 (compound 49) demonstrates a minor but considerable prolongation of KBT (kidney bleeding time) in cynomolgus monkeys and exhibits outstanding antithrombotic activity at a dose of 0.5 mg/kg [1][2].
In vivo, BMS-986141 demonstrates strong antithrombotic properties, making it a valuable tool for research within the fields of cardiovascular disease and thrombus formation. Its oral bioavailability enhances its utility in preclinical studies aimed at understanding the role of PAR-4 in various physiological and pathological processes. Specific in vivo efficacy data, such as effects in animal models of thrombosis, are not detailed in the available sources. |
| Enzyme Assay |
A cell-free assay for BMS-986141 would involve measuring its binding affinity to PAR-4 using radioligand binding assays with membrane preparations expressing the receptor. The compound's ability to displace a labeled PAR-4 ligand would be measured. Alternatively, its antagonistic activity could be assessed in cell-based functional assays measuring PAR-4-mediated signaling.
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| Cell Assay |
Cellular assays for BMS-986141 typically involve measuring its ability to inhibit PAR-4-mediated platelet aggregation. Platelet-rich plasma is incubated with the compound, and aggregation is induced with a PAR-4 agonist peptide. The inhibition of aggregation is measured using aggregometry. These assays confirm the compound's antiplatelet activity.
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| Animal Protocol |
Animal/Disease Models: Monkey arterial thrombosis (AT) and mesenteric bleeding time (MBT) model [2]
Doses: 0.05, 0.1, 0.5 mg/kg Route of Administration: po (po (oral gavage)) 2 hrs (hrs (hours)) Experimental Results: Inhibition of PAR4-AP-induced PAR4-AP in humans and monkeys The IC50 for platelet aggregation in blood is 1.8 and 1.3 nM respectively. In the AT model, thrombus weight was diminished by 36%, 63% and 88% at concentrations of 0.05, 0.1 and 0.5 mg/kg, respectively. MBT increased by 1.2 times. Animal/Disease Models: Rats, dogs and monkeys [1] Doses: 0.5, 1, 2 mpk Route of Administration: intravenous (iv) (iv)injection, 0.5 mpk, 10 minutes or po (po (oral gavage)) rats 2 mpk, dogs and monkeys 1 mpk Experimental Results: BMS drug Kinetic parameters - 986141 (Compound 49) Parameters Rat Dog Monkey t1/2(h) 3.7 ± 0.4 13 75 ± 12 CL (mL/min/kg) 14.3 ± 0.4 8.5 12 ± 2 Vss(L/kg) 2.7 ± 0.3 2.7 14 ± 5 fluorine (%) 31 25 36 In vivo animal experiments for BMS-986141 are not described in the available sources. As an orally active PAR-4 antagonist, it could be evaluated in animal models of thrombosis, such as the ferric chloride-induced arterial thrombosis model or the arteriovenous shunt model. However, no specific protocols or data are provided. |
| ADME/Pharmacokinetics |
BMS-986141 has a molecular formula of C27H23N5O5S2 and a molecular weight of 561.63 g/mol. It is an orally active compound. Specific pharmacokinetic parameters, such as half-life and bioavailability, are not provided in the available sources. The compound is intended for research use in cardiovascular disease and thrombus formation. For storage, the powder should be kept at -20°C for up to 3 years or at 4°C for up to 2 years.
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| Toxicity/Toxicokinetics |
Toxicity data for BMS-986141 are not provided in the available sources. As a research compound, it is intended for research use only and is not for human consumption. Standard laboratory safety precautions should be observed when handling this compound.
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| References |
[1]. E Scott Priestley, et al. Discovery of Two Novel Antiplatelet Clinical Candidates (BMS-986120 and BMS-986141) That Antagonize Protease-Activated Receptor 4. J Med Chem. 2022 Jul 14;65(13):8843-8854.
[2]. P Wong, et al. Favorable therapeutic index of an orally-active small-molecule antagonist of the platelet protease-activated receptor-4, BMS-986141, compared with the P2Y12 antagonist ticagrelor in cynomolgus monkeys. European Heart Journal, Volume 41, Iss |
| Additional Infomation |
BMS-986141 is being investigated in the clinical trial NCT02985632 (a study evaluating the pharmacokinetics of BMS-986141 in participants with impaired liver function and healthy participants).
BMS-986141 (CAS: 1478711-48-6) is a selective and potent PAR-4 antagonist. It is also known as UDM-003183. The compound has an IC50 of 0.4 nM and exhibits strong antithrombotic properties. It is used in research on cardiovascular disease and thrombus formation. It is not an approved drug and is strictly for research purposes. |
| Molecular Formula |
C27H23N5O5S2
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|---|---|
| Molecular Weight |
561.63
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| Exact Mass |
561.114
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| CAS # |
1478711-48-6
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| PubChem CID |
72188743
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| Appearance |
White to off-white solid powder
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| LogP |
4.9
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
39
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| Complexity |
851
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
KEEBLYWBELVGPQ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C27H23N5O5S2/c1-31(2)25(33)16-7-5-15(6-8-16)24-28-17(14-38-24)13-36-21-9-18(34-3)10-22-19(21)11-23(37-22)20-12-32-26(29-20)39-27(30-32)35-4/h5-12,14H,13H2,1-4H3
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| Chemical Name |
4-[4-[[6-methoxy-2-(2-methoxyimidazo[2,1-b][1,3,4]thiadiazol-6-yl)-1-benzofuran-4-yl]oxymethyl]-1,3-thiazol-2-yl]-N,N-dimethylbenzamide
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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 | 1.7805 mL | 8.9027 mL | 17.8053 mL | |
| 5 mM | 0.3561 mL | 1.7805 mL | 3.5611 mL | |
| 10 mM | 0.1781 mL | 0.8903 mL | 1.7805 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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