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Purity: ≥98%
BMS-986120 (BMS986120) is a novel, potent and orally bioactive antagonist of protease-activated receptor-4 (PAR4) with the potential to be used for thrombus propagation and pathological vascular occlusion. It inhibits PAR4 with IC50s of 9.5, 2.1 nM in human and monkey blood, respectively. BMS-986120 has finished a clinical trial in phase I. Human platelet thrombin receptor number is PAR4. BMS-986120's antithrombotic potential was investigated in cynomolgus monkey models of electrically-mediated carotid artery thrombosis and bleeding time (BT), as these monkeys have human-like platelet thrombin receptors. In primates, BMS-986120, either by itself or in conjunction with ASA, prevents occlusive carotid artery thrombosis with minimal effect on BT, indicating a broader therapeutic window than aspirin and clopidogrel, the antiplatelet medications of choice.
| Targets |
PAR4(Protease-Activated Receptor 4) [2].
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| ln Vitro |
BMS-986120 (BMS) comparably inhibits PA induced by PAR4-AP in vitro in both human and monkey blood (IC50 of 9.5±2.7 and 2.1±0.4 nM, respectively).
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| ln Vivo |
BMS-986120 causes simultaneous rightward shifts in the log PA dose response to PAR4-AP in monkeys, but it has no effect on the maximum response; this suggests that antagonism can be overcome. Selectivity is supported by the fact that BMS (1 mg/kg) does not inhibit PA brought on by collagen, ADP, and PAR1-AP. TW is lowered by 35±5, 49±4, and 83±4%, respectively, by BMS (0.2, 0.5, and 1 mg/kg). The maximum increases in KBT and MBT are only 2.2 and 1.8 times, respectively. A maximum antiplatelet dose of 4 mg/kg/h (n = 8) results in a slight reduction of TW by 12±2%, while KBT and MBT increase by 2.2 and 2.7 fold, respectively. Combined use of ASA and BMS (0.5 or 1 mg/kg) results in TW reductions of 54±3 and 95±2%, increases in KBT of 3.1 and 3.6 times, and increases in MBT of 2.6 and 3.3 times, for each group (n = 8). In studies involving companion monkeys, clopidogrel (0.3 mg/kg/day, n=6) by itself decreases TW by 49±6%, but it increases MBT and KBT by 8.1 and 7.3 times, respectively[1].
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| Animal Protocol |
Individual anesthetized monkeys were given orally of BMS (0.2, 0.5,1 mg/kg) or vehicle (n=8/group) 2 hour before a combination of thrombosis, BT and ex vivo biomarker experiments. Aspirin alone (ASA, 4 mg/kg/h IV) or in combination with BMS (0.5, 1 mg/kg) was also studied (n=8/group). Thrombus weight (TW) reduction, BT increase over vehicle in kidney (KBT) and mesenteric artery (MBT), and platelet aggregation (PA) inhibition were determined. Peak PA responses to activation peptides selective for PAR4 (PAR4-AP, 12.5 μM) and PAR1 (PAR1-AP, 18 μM), ADP (20 μM), and collagen (5 μg/ml) were determined by whole blood aggregometry.[1]
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| References |
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| Molecular Formula |
C23H23N5O5S2
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|---|---|
| Molecular Weight |
513.589222192764
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| Exact Mass |
513.11
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| Elemental Analysis |
C, 53.79; H, 4.51; N, 13.64; O, 15.58; S, 12.48
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| CAS # |
1478712-37-6
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| Appearance |
White to off-white solid powder
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| LogP |
4.2
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| tPSA |
153Ų
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| SMILES |
CC1=C(N=C(S1)N2CCOCC2)COC3=CC(=CC4=C3C=C(O4)C5=CN6C(=N5)SC(=N6)OC)OC
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| InChi Key |
MINMDCMSHDBHKG-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C23H23N5O5S2/c1-13-17(25-21(34-13)27-4-6-31-7-5-27)12-32-18-8-14(29-2)9-19-15(18)10-20(33-19)16-11-28-22(24-16)35-23(26-28)30-3/h8-11H,4-7,12H2,1-3H3
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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]-5-methyl-1,3-thiazol-2-yl]morpholine
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| Synonyms |
BMS 986120; BMS-986120; BMS986120.
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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) |
DMSO: ~3.3 mg/mL (~6.5 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 | 1.9471 mL | 9.7354 mL | 19.4708 mL | |
| 5 mM | 0.3894 mL | 1.9471 mL | 3.8942 mL | |
| 10 mM | 0.1947 mL | 0.9735 mL | 1.9471 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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT02439190 | Completed | Drug: BMS-986120 Drug: Aspirin |
Thrombosis | Bristol-Myers Squibb | September 2015 | Phase 1 |
| NCT02208882 | Completed | Drug: BMS-986120 Drug: Placebo Drug: Midazolam |
Healthy Adult Volunteers | Bristol-Myers Squibb | August 2014 | Phase 1 |
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