生物活性

• 描述Autotaxin (ATX) is an ectoenzyme that catalyzes the conversion of lysophosphatidylcholine (LPC) to lysophosphatidic acid (LPA), a bioactive lipid and a close relative of sphingosine 1-phosphate. High endothelial venules (HEVs) produce and secrete ATX into the blood^[3]. HA130 is a selective ATX inhibitor with an IC₅₀ of 28 nM^[3]. HA130 abolished the enhancing effect of ATX on TEM (transendothelial migration) and HA130 at 0.3 mM completely ablated the activity of ATX on TK1 uropod formation^[3]. When injecting CFSE-labeled T cells together with HA130 i.v. into mice and then reinjecting the drug at 7 and 12 min, SLOs (secondary lymphoid organs) were sectioned and stained to reveal HEVs after 15 min^[3]. The ratio of outside HEVs to inside HEVs was used as an index of T cell migration across HEVs. HA130 decreased the outside HEV/inside HEV ratio by 3–4-fold compared with vehicle treatment (p＜0.01 for both PLNs (peripheral lymph node) and MLNs (mesenteric lymph node)). This result is consistent with HA130 retarding the migration of T cells across LN (lymph node) HEVs^[3]. The s.c. administration of HA130 induces marked lymphocyte accumulation within the endothelial cell (EC) and sub-EC layers of HEVs in draining lymph nodes^[4].
• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT02461953	Renal Dialysis ... more >> Hemoperfusion Quality of Life Collapse <<	Not Applicable	Completed	-	China, Beijing ... more >> Chinese PLA General Hospital Beijing, Beijing, China, 100853 Collapse <<
  NCT02747979	Hyperparathyroidism ... more >> Refractory Pruritus Ostalgia Insomnia Collapse <<	Phase 2 Phase 3	Completed	-	China, Guangdong ... more >> The 1st Affiliated Hospital, Sun Yet-sen University Guangzhou, Guangdong, China, 510080 Collapse <<
  NCT03227770	End-stage Renal Disease	Not Applicable	Recruiting	December 31, 2019	China, Shanghai ... more >> Changhai Hospital Recruiting Shanghai, Shanghai, China, 200000 Contact: Zhiyong Guo, doctoral          Longhua Hospital Shanghai University of Traditional Chinese Medicine Recruiting Shanghai, Shanghai, China, 200000 Contact: Yueyi Deng, doctoral          RenJi Hospital Recruiting Shanghai, Shanghai, China, 200000 Contact: Zhaohui Ni, doctoral          Ruijin Hospital Recruiting Shanghai, Shanghai, China, 200000 Contact: Xiaonong Chen, doctoral          Shanghai 6th People's Hospital Recruiting Shanghai, Shanghai, China, 200000 Contact: Niansong Wang, doctoral          Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine Recruiting Shanghai, Shanghai, China, 200000 Contact: Weijie Yuan, doctoral          Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University Recruiting Shanghai, Shanghai, China, 200000 Contact: Feng Ding, doctoral          Shanghai Tongji Hospital, Tongji University School of Medicine Recruiting Shanghai, Shanghai, China, 200000 Contact: Chen Yu, doctoral          Shanghai Zhongshan Hospital Recruiting Shanghai, Shanghai, China, 200000 Contact: Xiaoqiang Ding, doctoral          Yangpu District Central Hospital Affiliated to Tongji University Recruiting Shanghai, Shanghai, China, 200000 Contact: Rong Zhou, doctoral          Xinhua Hospital, Shanghai Jiao Tong University School of Medicine Recruiting Shanghai, Shanghai, China, 200092 Contact: Wei LU, doctoral    +86-13651608106    luweixh@126.com Collapse <<

• 参考文献

• [1] Albers HM, van Meeteren LA, et al. Discovery and optimization of boronic acid based inhibitors of autotaxin. J Med Chem. 2010 Jul 8;53(13):4958-67.

  [2] Albers HM, Dong A, et al. Boronic acid-based inhibitor of autotaxin reveals rapid turnover of LPA in the circulation. Proc Natl Acad Sci U S A. 2010 Apr 20;107(16):7257-62.

  [3] Zhang Y, Chen YC, Krummel MF, Rosen SD. Autotaxin through lysophosphatidic acid stimulates polarization, motility, and transendothelial migration of naive T cells. J Immunol. 2012 Oct 15;189(8):3914-24. doi: 10.4049/jimmunol.1201604. Epub 2012 Sep 7. PMID: 22962684; PMCID: PMC3509168.

  [4] Bai Z, Cai L, Umemoto E, Takeda A, Tohya K, Komai Y, Veeraveedu PT, Hata E, Sugiura Y, Kubo A, Suematsu M, Hayasaka H, Okudaira S, Aoki J, Tanaka T, Albers HM, Ovaa H, Miyasaka M. Constitutive lymphocyte transmigration across the basal lamina of high endothelial venules is regulated by the autotaxin/lysophosphatidic acid axis. J Immunol. 2013 Mar 1;190(5):2036-48. doi: 10.4049/jimmunol.1202025. Epub 2013 Jan 30. PMID: 23365076.