BMS-262084 / BMS - LARVOL DELTA

Simulations and active learning enable efficient identification of an experimentally-validated broad coronavirus inhibitor. (PubMed, Nat Commun) - "Cell-based experiments confirmed BMS-262084's efficacy in blocking entry of various SARS-CoV-2 variants and other coronaviruses. The identified inhibitor holds promise for treating viral and other diseases involving TMPRSS2."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Choroid plexus mast cells drive tumor-associated hydrocephalus. (PubMed, Cell) - "BMS-262084, an inhibitor of tryptase, can cross the blood-brain barrier, inhibit TAH in vivo, and alleviate mast-cell-induced damage of epithelial cilia in a human pluripotent stem-cell-derived choroid plexus organoid model. Collectively, we uncover the function of CPMCs and provide an attractive therapy for TAH."

Journal • CNS Disorders • Oncology • Solid Tumor • Ventriculomegaly

Effect of factor XI inhibition on tumor cell-induced coagulation activation. (PubMed, J Thromb Haemost) - "Our findings indicate that FXI/FXIa inhibition interferes with tumor cell-induced coagulation activation only at low TF PCA expression levels, a finding with potential implications for future in-vivo studies."

Journal • Tumor cell • Cardiovascular • Hematological Disorders • Oncology • Thrombosis • Venous Thromboembolism

Paraneoplastic factor XI (FXI) production contributes to a hypercoagulable state in hepatic cancer and is a potential resistance mechanism against FXI/FXIa-directed anticoagulation (DGHO 2023) - "Tumor cell-induced coagulation activation was measured by single-stage clotting assay in the presence or absence of the FXIa inhibitor, BMS-262084 (BMS), or peak and trough concentrations of rivaroxaban (270 and 26 ng/mL) and tinzaparin (0.85 and 0.2 IU/mL). Conclusions : We suggest that FXI production is a common finding only in hepatic cancers. In this entity, however, dysregulated FXI synthesis can contribute to a hypercoagulable state and may critically affect the efficacy of FXI/FXIa-directed anticoagulation."

Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Liver Cancer • Oncology • Solid Tumor

Effect of factor XI/XIa inhibition in an in-vitro model of tumor cell-induced coagulation activation (DGHO 2023) - "Taken together, our study indicates that FXI/FXIa inhibition might be a promising approach in CAT prophylaxis and treatment, especially in tumors with weak TF PCA expression."

Preclinical • Tumor cell • Cardiovascular • Hematological Disorders • Oncology • Venous Thromboembolism

BMS-262084, a FXIa inhibitor, interferes with tumor cell-induced coagulation activation only in tumor cells with low tissue factor (TF) procoagulant activity (PCA) (#25) (GTH 2023) - "Coagulation activation by four distinct cancer cell lines (ie, BxPC-3, MCF-7, THP-1, and HL‑60) was analyzed by single-stage clotting and modified thrombin generation assay in the presence or absence of the FXIa inhibitor, BMS-262084, and peak or trough concentrations of tinzaparin (0.85 and 0.2 IU/mL) and rivaroxaban (270 and 26 ng/mL). Conclusion FXI inhibition predominantly interferes with the propagation phase of TF-triggered coagulation activation by tumor cells. Thus, the anticoagulant potency of FXI inhibitors may critically dependent on levels of TF expression by cancer cells, a finding with potential clinical implications for CAT prophylaxis and treatment."

Tumor cell • Cardiovascular • Hematological Disorders • Oncology • Venous Thromboembolism

Prevention of tumor cell-induced coagulation activation by the small-molecule FXIa inhibitor, BMS-262084, is dependent on tissue factor (TF) expression levels (ISTH 2022) - "BMS-262084 completely inhibited FXIa amidolytic activity at > 0.5 µM. In contrast to rivaroxaban and tinzaparin, 10 µM BMS-262084 mitigated the PCA of rhTF only at low rhTF concentrations. Under these conditions, the effect of BMS-262084 was comparable to that of peak tinzaparin and rivaroxaban levels."

Biomarker • Cardiovascular • Hematological Disorders • Oncology • Venous Thromboembolism