生物活性

• 描述Retinoic acid receptors (RARs) are members of the super‐family of nuclear hormone receptors, which directly regulate the transcription of their target genes in the nucleus. Retinoic acid, the active metabolite of vitamin A, is a ligand for retinoic acid receptor (RAR) and retinoid X receptor (RXR). It has pleiotropic effects on growth, differentiation, proliferation, and development, and determines embryonic pattern formation and inhibits tumor growth. Addition of tretinoin significantly suppressed the remarkably elevated MMP-13 mRNA expression in the keloid‐derived dermal fibroblasts, with the peak suppression at 12h^[3]. Tretinoin also prevented the cytotoxicity of H2O2 in cultured human mesangial cells by increasing both the catalase activity and the reduced glutathione content in dose- and time-dependent manner^[4]. Retinoic acid at 10 μM inhibited the migration of Aspc-1 and Panc-1 cells indirectly through its inhibitory effects on cancer associated fibroblasts (CAFs) and inhibited epithelial-mesenchymal transition of tumor cells by decreasing IL-6 secretion of CAFs^[5]. Neural stem cells (NSCs) treated with 1 µM retinoic acid for 4 days showed increased HRas and Tuj1 levels together with the increase in the active HRas level, which was required for NSC differentiation into neurons and murine brain development^[6].
• 细胞研究
• Cell Data

  Cell Lines	Concentration	Assay Type	Time	Activity Description	Data Sources
  COS7 cells	-	Function assay	16 h	Activity at human RARgamma ligand binding domain expressed in COS7 cells co-transfected with Gal4-DBD assessed as transcriptional activation after 16 hrs by Gal4 response element-driven luciferase reporter gene assay, EC50=0.0002 μM	19058965
  CV-1 cells	-	Function assay	-	Transcriptional activation in CV-1 cells expressing Retinoic acid receptor RAR gamma, EC50=0.0007 μM	7490725
  HL-60 cells	-	Function assay	-	Induction of transglutaminase (TGase) activity in HL-60 cells, EC50=0.005 μM	8784454

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• 动物研究
  剂量	Mice: 1 mg/kg - 10 mg/kg[3] (i.p.) Rat: 10 mg/kg, 15 mg/kg[4] (p.o.), 1 mg/kg - 50 mg/kg[5] (p.o.) Swiss mice: LD50 = 31 mg/kg (i.p.); 1100 mg/kg (p.o.)[6]
  给药途径	i.p., p.o.

• 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
  NCT03291080	Neuroblastoma	Phase 1 Phase 2	Recruiting	October 28, 2019	United Kingdom ... more >> Bruce Morland Not yet recruiting Birmingham, United Kingdom Contact: Bruce Moreland, MD          Dr Antony Ng Recruiting Bristol, United Kingdom Contact: Antony Ng, MD          Dr Amos Burke Recruiting Cambridge, United Kingdom Contact: Amos Burke, MD          Mark Brougham Not yet recruiting Edinburgh, United Kingdom Contact: Mark Brougham, MD          Dr Martin Elliott Recruiting Leeds, United Kingdom Contact: Martin Elliott, MD          Dr Lisa Howell Recruiting Liverpool, United Kingdom Contact: Lisa Howell, MD          Dr Guiseppe Barone Recruiting London, United Kingdom Contact: Guiseppe Barone, MD          Dr Guy Makin Recruiting Manchester, United Kingdom Dr Madhumita Dandapani Recruiting Nottingham, United Kingdom Kate Wheeler Not yet recruiting Oxford, United Kingdom Contact: Kate Wheeler, MD          Sucheta Vaidya Recruiting Sutton, United Kingdom Contact: Sucheta Vaidya, MD Collapse <<
  NCT01336387	Healthy, no Evidence of Diseas... more >>e Collapse <<	Phase 1	Terminated	-	United States, Wisconsin ... more >> University of Wisconsin Hospital and Clinics Madison, Wisconsin, United States, 53792 Collapse <<
  NCT00006220	Leukemia Lymp... more >>homa Multiple Myeloma and Plasma Cell Neoplasm Myelodysplastic Syndromes Collapse <<	Phase 1 Phase 2	Terminated(Study drug became c... more >>ommercially available.) Collapse <<	-	United States, Missouri ... more >> Washington University Barnard Cancer Center Saint Louis, Missouri, United States, 63110 Collapse <<

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• 参考文献

• [1] Uchida G, Yoshimura K, et al. Tretinoin reverses upregulation of matrix metalloproteinase-13 in human keloid-derived fibroblasts. Exp Dermatol. 2003;12 Suppl 2:35-42.

  [2] Manzano VM, Puyol MR, et al. Tretinoin prevents age-related renal changes and stimulates antioxidant defenses in cultured renal mesangial cells. J Pharmacol Exp Ther. 1999 Apr;289(1):123-32.

  [3] Uchida G, Yoshimura K, Kitano Y, Okazaki M, Harii K. Tretinoin reverses upregulation of matrix metalloproteinase-13 in human keloid-derived fibroblasts. Exp Dermatol. 2003;12 Suppl 2:35-42. doi: 10.1034/j.1600-0625.12.s2.6.x. PMID: 14756522.

  [4] Manzano VM, Puyol MR, Puyol DR, Cazaña FJ. Tretinoin prevents age-related renal changes and stimulates antioxidant defenses in cultured renal mesangial cells. J Pharmacol Exp Ther. 1999 Apr;289(1):123-32. PMID: 10086995.

  [5] Guan J, Zhang H, Wen Z, Gu Y, Cheng Y, Sun Y, Zhang T, Jia C, Lu Z, Chen J. Retinoic acid inhibits pancreatic cancer cell migration and EMT through the downregulation of IL-6 in cancer associated fibroblast cells. Cancer Lett. 2014 Apr 1;345(1):132-9. doi: 10.1016/j.canlet.2013.12.006. Epub 2013 Dec 12. PMID: 24334138.

  [6] Park JC, Jeong WJ, Kim MY, Min D, Choi KY. Retinoic-acid-mediated HRas stabilization induces neuronal differentiation of neural stem cells during brain development. J Cell Sci. 2016 Aug 1;129(15):2997-3007. doi: 10.1242/jcs.184366. Epub 2016 May 16. PMID: 27185863.

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