PCI-27483 is a reversible small-molecule activated factor VIIa (FVIIa) inhibitor[1-2]. PCI-27483 selectively inhibits the FVIIa/tissue factor (TF) complex, blocking PAR-2 activation and its downstream signaling pathways. PCI-27483 can be used in research related to cancer therapy, antiviral and antithrombotic applications[3-4].
In vitro, pretreatment of human Calu-3 2B4 airway epithelial cells with PCI-27483 (100μM) for 1 hour, followed by infection with pseudovirions bearing the SARS-CoV-2 spike glycoprotein, moderately inhibited pseudovirus entry[5]. PCI-27483 (4μM) was combined with an anti-VEGFA antibody to treat tumor-derived human umbilical vein endothelial cells for 4-48 hour. The combination significantly inhibited cell proliferation, migration, and tube-forming capability, while also reducing CPT1A protein levels in the tumor-derived human umbilical vein endothelial cells[6].
References:
[1] Gómez-Outes A, Suárez-Gea ML, Lecumberri R, et al. New parenteral anticoagulants in development. Ther Adv Cardiovasc Dis. 2011 Feb;5(1):33-59.
[2] Ramanathan RK, Thomas GW, Khorana AA, et al. A Phase 2 Study of PCI-27483, a Factor VIIa Inhibitor in Combination with Gemcitabine for Advanced Pancreatic Cancer. Oncology. 2019;96(4):217-222.
[3] Bonardi A, Supuran CT. Polypharmacology of carbonic anhydrase inhibitors and activators. Expert Opin Pharmacother. 2025 Apr;26(5):567-580.
[4] Shrimp JH, Janiszewski J, Chen CZ, et al. Suite of TMPRSS2 Assays for Screening Drug Repurposing Candidates as Potential Treatments of COVID-19.
[5] Sun YJ, Velez G, Parsons DE, et al. Structure-based phylogeny identifies avoralstat as a TMPRSS2 inhibitor that prevents SARS-CoV-2 infection in mice. J Clin Invest. 2021 May 17;131(10):e147973.
[6] Huang N, Ren J, Deng X, et al. PIEZO1 as a new target for hyperglycemic stress-induced neuropathic injury: The potential therapeutic role of bezafibrate. Biomed Pharmacother. 2024 Jul;176:116837.
PCI-27483是一种可逆的小分子活化因子VIIa（FVIIa）抑制剂[1-2]。PCI-27483选择性抑制FVIIa/组织因子（TF）复合物，阻断PAR-2激活及下游信号通路。PCI-27483可用于肿瘤治疗、抗病毒、抗血栓的相关研究[3-4]。
在体外，PCI-27483（100μM）预处理人Calu-3 2B4气道上皮细胞1小时，随后用带有SARS-CoV-2刺突糖蛋白的假病毒感染，可适度抑制假病毒的进入[5]。PCI-27483（4μM）与抗VEGFA抗体联合处理肿瘤人脐静脉内皮细胞4-48小时。PCI-27483可显著抑制细胞的增殖、迁移和成管能力，同时在肿瘤人脐静脉内皮细胞中降低CPT1A蛋白水平[6]。