KYP 2047
目录号 : GC50403
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。
Cas No.:796874-99-2
Sample solution is provided at 25 µL, 10mM.
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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]。
| Cell experiment [1]: | |
Cell lines | U-87 MG, U-138 MG, and A-172 human glioblastoma (GB) cell lines |
Preparation Method | GB cells were maintained in Dulbecco's modified Eagle's medium (DMEM) supplemented with 10% fetal bovine serum (FBS), antibiotics, and L-glutamine at 37°C, 5% CO₂. GB cells were treated with KYP 2047 at increasing concentrations (0.01-100µM) for 24 hours. |
Reaction Conditions | 0.01–100μM; 24 hours |
Applications | KYP 2047 significantly reduced cell viability in all three GB cell lines in a concentration-dependent manner. KYP 2047 also increased the expression of pro-apoptotic proteins Bax and p53, while decreasing the expression of anti-apoptotic protein Bcl-2. Additionally, KYP 2047 reduced transforming growth factor-β (TGF-β) expression and increased caspase-3 activation. |
| Animal experiment [2]: | |
Animal models | A30P α-synuclein transgenic mice (Thy1-A30P-α-syn) |
Preparation Method | Transgenic mice were intraperitoneally administered KYP 2047 (3mg/kg) twice daily for 5 days. Mice were sacrificed after treatment completion for brain tissue analysis. |
Dosage form | 3mg/kg; i.p.; twice daily for 5 days. |
Applications | KYP 2047 treatment significantly reduced α-synuclein immunoreactivity and soluble α-synuclein protein levels in multiple brain regions (striatum, substantia nigra, motor cortex). KYP 2047 also decreased α-synuclein/PREP colocalization and reduced high molecular weight SDS-insoluble α-synuclein oligomers in brain tissues. |
[1] 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. | |
| Cas No. | 796874-99-2 | SDF | |
| Canonical SMILES | O=C(N1CCC[C@H]1C#N)[C@@H]2CCCN2C(CCCC3=CC=CC=C3)=O | ||
| 分子式 | C20H25N3O2 | 分子量 | 339.44 |
| 溶解度 | Soluble in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.946 mL | 14.7301 mL | 29.4603 mL |
| 5 mM | 589.2 μL | 2.946 mL | 5.8921 mL |
| 10 mM | 294.6 μL | 1.473 mL | 2.946 mL |
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