KYP 2047 is a potent, blood-brain barrier permeable prolyl oligopeptidase (POP; Ki=0.023nM) inhibitor. By highly selectively inhibiting POP enzyme activity, KYP 2047 can modulate levels of neuropeptides in the brain that are associated with learning, memory, and neurodegenerative diseases[1-2]. KYP 2047 can be used in research related to neuropsychiatric disorders such as cognitive impairment, schizophrenia, and Alzheimer's diseases[3-4].
In vitro, KYP 2047 (0.01µM-100µM) treatment of human glioblastoma cells (U-87, A-172, U-138) for 24 hours, KYP 2047 significantly reduced cell viability, upregulated the expression of pro-apoptotic proteins Bax, p53, and caspase-3, while downregulated the expression of anti-apoptotic protein Bcl-2; KYP 2047 inhibited the expression of vascular endothelial growth factor (VEGF), endothelial nitric oxide synthase (eNOS), and transforming growth factor-β (TGF-β), and reduced Matrigel tubule formation[5]. KYP 2047 (50µM and 100µM) treatment of tongue squamous cell carcinoma cells (CAL27, HSC-2, HSC-3) for 24 hours, KYP 2047 significantly inhibited cell viability, promoted the expression of Bax, Bad, and caspase-3, reduced the levels of Bcl-2 and mutant p53, and inhibited the expression of VEGF, eNOS, and TGF-β[6].
In vivo, KYP 2047 (3mg/kg/day; intraperitoneal injection twice daily) treatment of A30P α-synuclein transgenic mice for 5 days, KYP 2047 significantly reduced soluble and insoluble α-synuclein levels in the brain, decreased α-synuclein immunoreactivity and aggregation, and improved neuronal survival[7]. KYP 2047 (2.5mg/kg/day or 5mg/kg/day; intraperitoneal injection) treatment of bleomycin-induced pulmonary fibrosis mice for 12 days, KYP 2047 significantly alleviated lung tissue fibrosis, collagen deposition, and inflammatory cell infiltration, reduced the expression of pro-fibrotic factors such as TGF-β and VEGF, and modulated the JAK2/STAT3 and NF-κB signaling pathways[8].
References:
[1] Xu P, Bao R, Zhang Y, et al. Prolyl oligopeptidase regulates progesterone secretion via the ERK signaling pathway in murine luteal cells. Mol Reprod Dev. 2019 Jun;86(6):714-726.
[2] Jalkanen AJ, Puttonen KA, Venäläinen JI, et al. Beneficial effect of prolyl oligopeptidase inhibition on spatial memory in young but not in old scopolamine-treated rats. Basic Clin Pharmacol Toxicol. 2007 Feb;100(2):132-8.
[3] Jalkanen AJ, Leikas JV, Forsberg MM. KYP-2047 penetrates mouse brain and effectively inhibits mouse prolyl oligopeptidase. Basic Clin Pharmacol Toxicol. 2014 Jun;114(6):460-3.
[4] Cucinotta L, Palermo N, Ardizzone A, et al. The Inhibition of Prolyl Endopeptidase (PREP) by KYP-2047 Treatment to Reduce Myocardial Ischemia/Reperfusion Injury. Antioxidants (Basel). 2025 Apr 8;14(4):442.
[5] Scuderi SA, Casili G, Ardizzone A, et al. KYP-2047, an Inhibitor of Prolyl-Oligopeptidase, Reduces GlioBlastoma Proliferation through Angiogenesis and Apoptosis Modulation. Cancers (Basel). 2021 Jul 9;13(14):3444.
[6] Scuderi SA, Casili G, Filippone A, et al. Beneficial effect of KYP-2047, a propyl-oligopeptidase inhibitor, on oral squamous cell carcinoma. Oncotarget. 2021 Dec 7;12(25):2459-2473.
[7] Myöhänen TT, Hannula MJ, Van Elzen R, et al. A prolyl oligopeptidase inhibitor, KYP-2047, reduces α-synuclein protein levels and aggregates in cellular and animal models of Parkinson's disease. Br J Pharmacol. 2012 Jun;166(3):1097-113.
[8] Cucinotta L, Mannino D, Casili G, et al. Prolyl oligopeptidase inhibition ameliorates experimental pulmonary fibrosis both in vivo and in vitro. Respir Res. 2023 Aug 25;24(1):211.
KYP 2047是一种有效的、可透过血脑屏障的prolyl oligopeptidase（POP；Ki=0.023nM）抑制剂，KYP 2047通过高选择性地抑制POP酶活性，能调节大脑中与学习记忆、神经退行性疾病相关的神经肽水平[1-2]。KYP 2047可用于认知功能障碍、精神分裂症和阿尔茨海默病等相关神经精神疾病的研究[3-4]。
在体外，KYP 2047（0.01μM-100μM）处理人胶质母细胞瘤细胞（U‑87、A‑172、U‑138）24小时，KYP 2047显著降低细胞活力，并上调促凋亡蛋白Bax、p53和caspase‑3表达，同时下调抗凋亡蛋白Bcl‑2表达； KYP 2047抑制血管内皮生长因子（VEGF）、内皮型一氧化氮合酶（eNOS）及转化生长因子‑β（TGF‑β）的表达，并减少基质胶管状结构形成[5]。KYP 2047（50μM和100μM）处理舌鳞状细胞癌细胞（CAL27、HSC‑2、HSC‑3）24小时，KYP 2047显著抑制细胞活力，促进Bax、Bad和caspase‑3表达，降低Bcl‑2和突变型p53水平，并抑制VEGF、eNOS和TGF‑β的表达[6]。
在体内，KYP 2047（3mg/kg/day；每日两次腹腔注射）处理A30P α-突触核蛋白转基因小鼠5天，KYP 2047显著降低脑内可溶性和不溶性α-突触核蛋白水平，减少α-突触核蛋白免疫反应性和聚集，并改善神经元存活[7]。KYP 2047（2.5mg/kg/day或5mg/kg/day；腹腔注射）处理博来霉素诱导的肺纤维化小鼠12天，KYP 2047显著减轻肺组织纤维化、胶原沉积和炎症细胞浸润，降低TGF-β、VEGF等促纤维化因子表达，并调节JAK2/STAT3和NF-κB信号通路[8]。