Ac-Gly-BoroPro is a selective Fibroblast Activation Protein (FAP) inhibitor with a Ki of 23nM[1, 2]. Ac-Gly-BoroPro selectively inhibits FAP, compared to other proline peptidases[3, 4], which is an important biomarker for cancer-associated fibroblasts and activated fibroblasts. FAP reacts readily with submicromolar concentrations of Ac-Gly-BoroPro, reaching steady state inhibition levels rapidly (Ki=23±3nM)[2].
Ac-Gly-BoroPro (10μM; 24h or 48h) can inhibit Human periodontal ligament stem cells (hPDLSCs) proliferation and migration[5]. Ac-Gly-BoroPro (20μM; 7 days) can inhibit osteoclast differentiation[6].
Ac-Gly-BoroPro (500μg/kg; 35 days; intraperitoneal injection) was administered to 2-month-old unmated female mice with ovariectomized ovaries, which could alleviate osteoporosis induced by ovariectomy, promote bone formation, and inhibit bone resorption in mice[6]. Ac-Gly-BoroPro (40μg/kg; 4 weeks; intra-articular injection) could significantly improve cartilage erosion, subchondral bone thickening and osteophyte formation in destabilization of the medial meniscus (DMM) mice model[7].
References:
[1] HENDERSON J M, XIANG M S W, HUANG J C, et al. Dipeptidyl Peptidase Inhibition Enhances CD8 T Cell Recruitment and Activates Intrahepatic Inflammasome in a Murine Model of Hepatocellular Carcinoma [J]. Cancers (Basel), 2021, 13(21):
[2] HU Y, MA L, WU M, et al. Synthesis and structure-activity relationship of N-alkyl Gly-boro-Pro inhibitors of DPP4, FAP, and DPP7 [J]. Bioorg Med Chem Lett, 2005, 15(19): 4239-42.
[3] ZHAO L, CHEN J, PANG Y, et al. Fibroblast activation protein-based theranostics in cancer research: A state-of-the-art review [J]. Theranostics, 2022, 12(4): 1557-69.
[4] KIM S M, JANG Y J. Enzymatic activity of fibroblast activation protein-alpha is essential for TGF-beta1-induced fibroblastic differentiation of human periodontal ligament cells [J]. Exp Cell Res, 2024, 442(2): 114230.
[5] HE J, FANG B, SHAN S, et al. Mechanical stiffness promotes skin fibrosis through FAPalpha-AKT signaling pathway [J]. J Dermatol Sci, 2024, 113(2): 51-61.
[6] WEI H, XU Y, WANG Y, et al. Identification of Fibroblast Activation Protein as an Osteogenic Suppressor and Anti-osteoporosis Drug Target [J]. Cell Rep, 2020, 33(2): 108252.
[7] FAN A, WU G, WANG J, et al. Inhibition of fibroblast activation protein ameliorates cartilage matrix degradation and osteoarthritis progression [J]. Bone Res, 2023, 11(1): 3.