| Size | Price | Stock | Qty |
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| Other Sizes |
| Targets |
Factor XIa (FXIa). Milvexian is a highly selective and reversible inhibitor of the activated form of factor XI (FXIa), a serine protease in the intrinsic pathway of the coagulation cascade. It binds directly to the active site of FXIa. By inhibiting FXIa, milvexian blocks the amplification loop of thrombin generation, reducing the formation of fibrin clots. Because FXI is primarily involved in pathological thrombus formation rather than normal hemostasis, FXIa inhibition is expected to decouple antithrombotic efficacy from bleeding risk, offering a potentially safer profile than traditional anticoagulants.
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| ln Vitro |
Milvexian (about 10 μM) has no effect on collagen in ADP, arachidonic acid, or human activation, although it can lengthen the activation period of partial powder activation [1].
In cell-free biochemical assays, milvexian directly inhibits human and rabbit factor XIa with Ki values of 0.11 nM and 0.38 nM, respectively. It demonstrates high selectivity for FXIa over other coagulation factors (e.g., FXI, FVIIa, FXa, thrombin, plasmin) and over a broad panel of >100 proteases and kinases. The inhibitory activity is measured using a chromogenic or fluorogenic substrate assay. Inhibition is reversible and competitive with respect to the substrate. The compound shows similar potency against dog and rat FXIa, but slightly weaker against mouse FXIa, indicating species selectivity. |
| ln Vivo |
At one and two days following modeling, the mean venous concentrations of mildvexian (20 mg/kg, intravenous) were 2000 and 40 nM, respectively [1]. Milvexian (intravenous infusion, 0.8 mg/kg) For an average of roughly 10 minutes and 8 hours, mildvexian (0.063-4 + 0.04-2.68 mg/kg, intravenous infusion plus continuous intravenous infusion) can suppress thrombosis [2]. Rabbit pharmacokinetics. Examination [1] The dosage by route (mg/kg) Resolved (mL/min/kg) Distribution volume (L/kgL) Half-life (h) % of oral bioavailability iv/po 18 6.7 1.4 2.5 14
Milvexian is not typically tested in cellular assays because its target, FXIa, is a plasma protein. However, its activity is assessed in human plasma-based functional assays. It prolongs the activated partial thromboplastin time (aPTT) in a dose-dependent manner, while having a minimal effect on the prothrombin time (PT). This selectivity confirms its mechanism of action on the intrinsic pathway. In whole blood assays, it inhibits thrombus formation under flow conditions (e.g., using a perfusion chamber) and reduces clot weight and stability. The IC50 for aPTT prolongation is in the sub-micromolar range, consistent with its potent FXIa inhibition. |
| Enzyme Assay |
FXIa enzymatic activity is measured using a chromogenic assay format. Recombinant human FXIa is incubated with varying concentrations of milvexian (0.001-1000 nM) in Tris-buffered saline (pH 7.4) at room temperature for 10-60 minutes. A chromogenic substrate specific for FXIa (e.g., S-2366, pyroGlu-Pro-Arg-pNA) is added, and the absorbance at 405 nm is monitored over time as the substrate is cleaved, releasing p-nitroaniline. The initial linear velocity is plotted against inhibitor concentration to generate an inhibition curve. The Ki is determined from the IC50 using the Cheng-Prusoff equation for competitive inhibition, considering the substrate concentration and the Km of the enzyme.
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| Cell Assay |
Milvexian is not typically used in standard cell culture experiments, as its target is a plasma serine protease. Functional assays in plasma or whole blood are used instead. For ex vivo pharmacodynamic assays, human whole blood is collected in sodium citrate tubes and spiked with milvexian (0.001-10 uM). The aPTT (activated partial thromboplastin time) is measured using a coagulation analyzer, which detects clot formation by the change in turbidity or by electromechanical means. The PT (prothrombin time) is also measured as a control. The effect of milvexian on thrombus formation is assessed by perfusing whole blood over a collagen-coated surface under arterial shear rates (e.g., 1500 s-¹) using a microfluidic device, and platelet and fibrin deposition is quantified by fluorescence microscopy.
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| Animal Protocol |
Animal/Disease Models: Rabbit electrically mediated carotid thrombosis model [1]
Doses: Prevention: 0.063 + 0.04, 0.25 + 0.17 and 1 + 0.67 (mg/kg + mg/kg/h) Treatment: 0.25 + 0.17 and 1 + 0.67 ( mg /kg + mg/kg/h) Route of Administration: intravenous (iv) (iv)injection plus continuous infusion. Experimental Results: Carotid blood flow (CBF) was diminished to 32-76%, and thrombus weight was diminished by 15-70%. CBF diminished to 40% of control value after 15 minutes. After seventy-five minutes CBF diminished to 39-66%. Animal/Disease Models: Rabbit cuticle bleeding time model [1] Doses: Prevention: 0.063+0.04, 0.25+0.17, 1+0.67 (mg/kg+mg/kg/h) Prevention: 0.063+0.04, 0.25+0.17, 1 + 0.67 (mg/kg + mg/kg/h) Treatment: 0.25 + 0.17 and 1 + 0.67 (mg/kg + mg/kg/h) Route of Administration: intravenous (iv) (iv)(iv) plus continuous infusion Experimental Results: Not coadministered with aspirin Can increase carotid blood flow (BT). Animal/Disease Models: Rabbit arteriovenous shunt model [2] Doses: Prevention: 0.063 + 0.04, 0.25 + 0.17, 1 + 0.67 (mg/kg + mg/kg/h) Prevention: 0.063 + 0.04, 0.25 + 0.17, 1 + 0.67 (mg/kg + mg/kg/h) 0.25 + 0.17, 1.0 + 0.67 and 4.0 + 2.68 mg/kg Route of Administration: intravenous (iv) (iv)injection plus continuous infusion Experimental Results: thrombus weight diminished by 34.3 -66.9%. APTT prolongation time increased 1.54-3.12 times, but did not change PT and TT. In vivo antithrombotic efficacy of milvexian has been demonstrated in various animal models. In a rabbit model of electrically-induced carotid artery thrombosis, oral administration of milvexian (0.1-1 mg/kg) dose-dependently reduces thrombus weight and vessel occlusion. In a rat model of venous thrombosis (e.g., inferior vena cava stenosis), it reduces thrombus formation with a minimal effect on bleeding time compared to FXa or thrombin inhibitors. In cynomolgus monkeys, milvexian is shown to be effective in an arteriovenous shunt thrombosis model. The typical dosing route is oral gavage, with doses ranging from 0.1-30 mg/kg once or twice daily. The primary endpoint is thrombus mass or time to occlusion. |
| ADME/Pharmacokinetics |
Milvexian is orally bioavailable in preclinical species and humans. In healthy volunteers, after a single oral dose of 25-200 mg, the compound is rapidly absorbed, with a Tmax of 1-3 hours. It has a terminal elimination half-life (t1/2) of approximately 5-15 hours, supporting once- or twice-daily dosing. The oral bioavailability is high (>50%). Milvexian is moderately bound to plasma proteins (approx. 80-90%). It is metabolized primarily by CYP3A4, and its clearance is largely non-renal, although a fraction is excreted unchanged in the urine. Food has minimal effect on its absorption. The exposure (AUC) increases dose-proportionally. The PK profile in animals is consistent: in dogs, for example, the Tmax is 1.6 h, and half-life is 6.0 h.
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| Toxicity/Toxicokinetics |
In preclinical toxicology studies, milvexian has demonstrated a favorable safety profile with a wide therapeutic window. At antithrombotic doses, there is no significant increase in bleeding time in animal models, consistent with its FXIa mechanism. In repeated-dose toxicity studies in rats and dogs (up to 28-90 days), no major target organ toxicity was observed. It is not genotoxic, not teratogenic, and does not cause QT prolongation. In clinical trials to date, milvexian has been generally well-tolerated, with bleeding rates comparable to placebo at certain doses. The most common adverse events have been minor bleeding (e.g., bruising) and gastrointestinal symptoms.
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| References |
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| Additional Infomation |
Milvexian is being studied in the clinical trial NCT03766581 (a study on BMS-986177 for the prevention of stroke in patients taking aspirin and clopidogrel).
Milvexian is a collaboration between Bristol-Myers Squibb and Johnson & Johnson (Janssen). It is the most advanced oral FXIa inhibitor in clinical development. As of 2025, milvexian is in Phase 3 clinical trials (e.g., LIBREXIA) for the prevention of stroke in atrial fibrillation, secondary prevention in acute myocardial infarction, and treatment of acute coronary syndrome. It has received FDA Fast Track designation. The compound is also known by the chemical name BMS-986177. It is not yet approved by any regulatory agency. For research use, it is a valuable tool for studying the role of FXIa in thrombosis. The molecular formula is C28H23Cl2F2N9O2, and the molecular weight is 626.44. |
| Molecular Formula |
C28H23CL2F2N9O2
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| Molecular Weight |
626.4441
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| Exact Mass |
625.131
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| CAS # |
1802425-99-5
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| Related CAS # |
1802426-00-1 (TFA);1802425-99-5;
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| PubChem CID |
118277544
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| Appearance |
White to off-white solid powder
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| Density |
1.60±0.1 g/cm3
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| LogP |
4
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
43
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| Complexity |
1100
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| Defined Atom Stereocenter Count |
2
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| SMILES |
C[C@@H]1CCC[C@@H](C2=NC=CC(=C2)C3=C(C=NN3C(F)F)NC1=O)N4C=NC(=CC4=O)C5=C(C=CC(=C5)Cl)N6C=C(N=N6)Cl
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| InChi Key |
FSWFYCYPTDLKON-CMJOXMDJSA-N
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| InChi Code |
InChI=1S/C28H23Cl2F2N9O2/c1-15-3-2-4-23(20-9-16(7-8-33-20)26-21(36-27(15)43)12-35-41(26)28(31)32)39-14-34-19(11-25(39)42)18-10-17(29)5-6-22(18)40-13-24(30)37-38-40/h5-15,23,28H,2-4H2,1H3,(H,36,43)/t15-,23+/m1/s1
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| Chemical Name |
(9R,13S)-13-[4-[5-chloro-2-(4-chlorotriazol-1-yl)phenyl]-6-oxopyrimidin-1-yl]-3-(difluoromethyl)-9-methyl-3,4,7,15-tetrazatricyclo[12.3.1.02,6]octadeca-1(18),2(6),4,14,16-pentaen-8-one
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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 : ≥ 100 mg/mL (~159.63 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 | 1.5963 mL | 7.9816 mL | 15.9632 mL | |
| 5 mM | 0.3193 mL | 1.5963 mL | 3.1926 mL | |
| 10 mM | 0.1596 mL | 0.7982 mL | 1.5963 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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