Milvexian(CAS:1802425-99-5)

Milvexian (CAS 1802425-99-5, code BMS-986177) is co-discovered and developed by Bristol-Myers Squibb and Janssen Pharmaceuticals, a groundbreaking first-in-class reversible small-molecule FXIa inhibitor reshaping the anticoagulant landscape over the past decade. It addresses the long-standing therapeutic dilemma that conventional oral anticoagulants cannot decouple antithrombotic efficacy from bleeding risk, and is currently undergoing global Phase 3 LIBREXIA clinical programs. It has become an indispensable core research API for universities, CRO laboratories and innovative pharmaceutical enterprises studying thrombotic disorders and developing new-generation low-bleeding anticoagulant formulations. With molecular formula C₂₈H₂₃Cl₂F₂N₉O₂ and molecular weight 626.44, it appears as off-white crystalline powder with stable chemical scaffold and three-year shelf life under light-shielded -20℃ storage. HPLC purity consistently exceeds 99%, with rigorous control over chiral impurities, related substances, heavy metals and residual solvents. Its good solubility in DMSO supports in vitro cellular coagulation function assays, while oral suspension is applicable for rat and mouse thrombosis animal modeling, covering full research workflows including molecular target validation, high-throughput compound screening and efficacy/bleeding risk evaluation.

In terms of core pharmacological mechanism, human coagulation relies on two independent cascades: the extrinsic pathway activated by tissue injury is essential for physiological wound hemostasis, whereas the intrinsic FXIa cascade merely amplifies pathological thrombus without participating in baseline bleeding control. Traditional warfarin, FXa inhibitors and direct thrombin inhibitors block both pathways simultaneously, leading to a positive correlation between antithrombotic potency and hemorrhage liability. Milvexian exhibits ultra-high target affinity with human FXIa Ki = 0.11 nM, hundreds-fold selective over off-target proteases such as plasma kallikrein and chymotrypsin. It reversibly occupies the catalytic pocket of FXIa to block factor IX activation and cut off intrinsic coagulation amplification, drastically reducing thrombin generation and fibrin deposition. Meanwhile, tissue factor-triggered extrinsic coagulation remains fully intact to preserve normal hemostasis after visceral or cutaneous trauma, realizing a unique therapeutic profile of “preventing pathological thrombosis without impairing physiological bleeding control”. Preclinical animal studies demonstrated over 60% reduction in major bleeding events compared with FXa inhibitors under equivalent antithrombotic potency. It delivers stable oral absorption, moderate half-life and low renal clearance, requiring minimal dosage adjustment for mild-moderate renal impairment with limited drug-drug interaction risks, showing superior safety when combined with antiplatelet agents.

Clinically and scientifically, Milvexian covers four core research verticals. First, stroke prophylaxis in atrial fibrillation, with Phase 3 LIBREXIA-AF trial verifying its differentiated benefit of lowering ischemic stroke while cutting intracranial hemorrhage versus standard anticoagulants. Second, secondary prevention for acute coronary syndrome and ischemic stroke, reducing recurrent thrombotic events as add-on therapy to dual antiplatelet regimens. Third, venous thromboembolism prophylaxis after orthopedic and general surgery, resolving bleeding concerns in elderly postoperative populations. Fourth, it acts as a universal positive reference tool compound for FXIa lead compound activity screening, coagulation cascade mechanistic dissection and head-to-head bleeding risk comparison among various anticoagulants. Extensive epidemiological literature confirms patients with congenital FXI deficiency possess drastically lower thrombotic incidence without spontaneous bleeding, providing solid human clinical evidence supporting the rationality of FXIa as a therapeutic target.

Regarding raw material supply and industrial research value, Milvexian adopts patent-optimized total synthesis and purification technology to efficiently remove halogenated triazole structural impurities, delivering uniform in-vitro inhibitory activity across batches. Supply specifications range from milligram to kilogram scale, fully matching all demands from lab-scale screening to preclinical large-scale efficacy studies. Long-term in-vivo administration produces no obvious liver or kidney cumulative toxicity with a wide safe experimental window, suitable for prolonged intervention on chronic thrombosis animal models. With continuously expanding global patient populations suffering from atrial fibrillation, cerebral infarction and postoperative thromboembolism, novel oral anticoagulants with low bleeding risk stand at the forefront of innovative drug R&D, driving steady rising demand for FXIa-target tool compounds. Endowed with pioneering target novelty, comprehensive Phase 1/2/3 clinical datasets and superior separation of antithrombotic and hemorrhagic effects, Milvexian maintains irreplaceable long-term market competitiveness in cardiovascular thrombosis pharmacology, new-generation anticoagulant innovative and generic drug development, and fundamental coagulation research, promising broad sustainable development prospects across the global pharmaceutical industry.