SP-13786 is a potent and highly selective inhibitor of fibroblast activation protein (FAP) and prolyl oligopeptidase (PREP) (FAP: IC50 = 3.2nM; PREP: IC50 = 1.8μM) [1]. SP-13786 inhibits FAP's serine protease activity by binding to its catalytic site, thereby inhibiting FAP's function in tumor stroma or fibrotic tissue [2]. SP-13786 is used to study the role of FAP in tumors, fibrosis, and other pathological processes [3-4].
In MGC803 cells, Co-incubation with SP-13786 (10μM; 24h) significantly reduced the antitumor activity of cresyl violet (CV)-FAP [5]. In U87MG-Fluc cells, SP-13786 (50μM, 100μM; 30min) reduces intracellular FAP levels [6].
In BALB/c mice, SP-13786 (10mg/kg; iv; signle injection) targets and inhibits FAPα activity [7]. In myocardial infarction (MI) mouse model, SP-13786 (0.5mg/kg; ip; 7d) inhibits FAP and significantly improves cardiac function and promotes angiogenesis after MI [8].
References:
[1]. Jansen K, Heirbaut L, Verkerk R, et al. Extended structure–activity relationship and pharmacokinetic investigation of (4-quinolinoyl) glycyl-2-cyanopyrrolidine inhibitors of fibroblast activation protein (FAP)[J]. Journal of medicinal chemistry, 2014, 57(7): 3053-3074.
[2]. Kiani M, Jokar S, Hassanzadeh L, et al. Recent clinical implications of FAPI: imaging and therapy[J]. Clinical nuclear medicine, 2022: 10.1097.
[3]. Butuzova D A, Kulebyakina M A, Basalova N A, et al. Fibroblast Activation Protein Alpha (FAPα) as a Promising Target in the Diagnostics and Treatment of Cancer and Fibrotic Diseases: Recent Approaches to Imaging and Assessment of Functional Activity[J]. Biochemistry (Moscow), 2025, 90(Suppl 1): S135-S145.
[4]. Zhou Y, Yin K, Dong H, et al. Long-lasting bioluminescence imaging of the fibroblast activation protein by an amphiphilic block copolymer-based probe[J]. Analytical Chemistry, 2021, 93(8): 3726-3732.
[5]. Liu S Y, Wang H, Nie G. Ultrasensitive fibroblast activation protein-α-activated fluorogenic probe enables selective imaging and killing of melanoma in vivo[J]. ACS sensors, 2022, 7(7): 1837-1846.
[6]. Lin Y, Ma Z, Li Z, et al. Bioluminescent probe for monitoring endogenous fibroblast activation protein-alpha[J]. Analytical Chemistry, 2019, 91(23): 14873-14878.
[7]. Fu A, Wang H, Huo T, et al. A novel chemiluminescence probe for sensitive detection of fibroblast activation protein-alpha in vitro and in living systems[J]. Analytical Chemistry, 2021, 93(16): 6501-6507.
[8]. Sun Y, Ma M, Cao D, et al. Inhibition of fap promotes cardiac repair by stabilizing BNP[J]. Circulation research, 2023, 132(5): 586-600.
SP-13786是一种强效、高选择性的成纤维细胞活化蛋白（FAP）和脯氨酰寡肽酶（PREP）抑制剂（FAP: IC50 = 3.2nM; PREP: IC50 = 1.8μM) [1]。SP-13786通过结合FAP的催化位点抑制其丝氨酸蛋白酶活性，从而抑制FAP在肿瘤基质或纤维化组织中的功能 [2]。SP-13786用于研究FAP在肿瘤、纤维化和其他病理过程中的作用 [3-4]。
在MGC803细胞中，与SP-13786（10μM；24h）共孵育可显著降低甲酚紫（CV）-FAP的抗肿瘤活性 [5]。在U87MG-Fluc细胞中，SP-13786（50μM，100μM；30min）可降低细胞内FAP水平 [6]。
在BALB/c小鼠中，SP-13786（10mg/kg；iv；单次注射）靶向抑制FAPα活性 [7]。在心肌梗死（MI）小鼠模型中，SP-13786（0.5mg/kg；ip；7d）可抑制FAP，显著改善心肌功能，并促进心肌梗死后的血管生成 [8]。