产品描述: | KGP94 is a selective inhibitor of cathepsin L with an IC50 of 189 nM. KGP94 inhibits migration and invasion of metastatic carcinoma and shows low cytotoxicity (GI50=26.9 µM) against various human cell lines |
靶点: |
189 nM (cathepsin L);CysteineProtease |
体外研究: |
KGP94 (10 or 20 μM, 24 h) reduces expression of M2 (macrophage) markers (Arginase-1 and CD206) and cells invasion of primary bone marrow-derived macrophages or Raw264.7.
KGP94 (25 μM, 24 h) impairs the incasive capacities of both prostate and breat cancer cells by 53% and 88%, respectively.
KGP94 (25 μM, 24 h) suppresses secreted CTSL activity by 94% and 92% in PC-3ML and MDA-MB-231, repsectively. |
体内研究: |
KGP94 (i.p.; 20 mg/kg; once daily for 3 days) exhibits anti-metastatic and anti-bone resorptive efficacy in a prostate cancer bone metastasis model. Animal Model: NCR nu/nu male mice Dosage: 20 mg/kg Administration: Intraperitoneal injection; once daily for 3 days Result: Reduced 65% in metastatic tumor burden and 58% in tumor angiogenesis, improved survival of bone metastases bearing mice. |
参考文献: |
1. Parker EN, et al. Synthesis and biological evaluation of a water-soluble phosphate prodrug salt and structural analogues of KGP94, a lead inhibitor of cathepsin L. Bioorg Med Chem Lett. 2017 Mar 1. 27(5):1304-1310.
2. Munikishore R, et al. An efficient and concise synthesis of a selective small molecule non-peptide inhibitor of cathepsin L: KGP94. Bioorg Chem. 2021 Nov. 116:105317.
3. Dykes SS, et al. Cathepsin L secretion by host and neoplastic cells potentiates invasion. Oncotarget. 2019 Sep 17. 10(53):5560-5568.
4. Sudhan DR, et al. Cathepsin L inhibition by the small molecule KGP94 suppresses tumor microenvironment enhanced metastasis associated cell functions of prostate and breast cancer cells. Clin Exp Metastasis. 2013 Oct. 30(7):891-902.
5. Sudhan DR, et al. Cathepsin L inactivation leads to multimodal inhibition of prostate cancer cell dissemination in a preclinical bone metastasis model. Int J Cancer. 2016 Jun 1;138(11):2665-77. |
溶解性: |
Soluble in DMSO |
保存条件: |
-20℃ |
备注: |
KGP94 是一种特异的 cathepsin L 抑制剂,IC50为 189 nM。KGP94 抑制转移癌的运动性和侵袭性,对人类细胞的毒性低 (GI50=26.9µM)。 |
配置溶液浓度参考: |
|
1mg |
5mg |
10mg |
1 mM |
2.855 ml |
14.276 ml |
28.553 ml |
5 mM |
0.571 ml |
2.855 ml |
5.711 ml |
10 mM |
0.286 ml |
1.428 ml |
2.855 ml |
50 mM |
0.057 ml |
0.286 ml |
0.571 ml |
|
注意: |
部分产品我司仅能提供部分信息,我司不保证所提供信息的权威性,仅供客户参考交流研究之用。 |