生物活性

• 描述Retinoid acid (RA) is a metabolite of retinol that plays an important role in cell growth and differentiation. The retinoic acid receptors (RARs) and retinoid X receptors (RXRs) are two classes of nuclear receptors mediating the regulation of RA and its derivatives on gene expression. Tamibarotene is a RAR agonist selective for RARa with an K_d value of 62 nM and an AC₅₀ value of 1.46 nM compared to RARb (K_d = 280 nM, AC₅₀ = 6.87 nM) and RARg (K_d = 816 nM, AC₅₀ = 148.66 nM)^[3]. Incubation of HL-60 cells with tamibarotene (100 nM – 10 μM) for 9 days significantly decreased the total cell number and increased the number of dead cells at a time-dependent manner. The percentage of growth inhibition induced by 100 nM tamibarotene after 9-day incubation was 32.0, 23.7, 27.9, and 59.2% in HL60R, K562, Kasumi-1, and Meg01 cells, respectively. Tamibarotene at 10, 20, and 40 μM also induced the secretion of TGF-b2 in K562, MOLT3, Raji, and U937 cell lines with an incubation period of 3 days. Moreover, 3-day treatment of tamibarotene from 10 – 40 μM in Raji cells increased the expression ratio of phosphorylated Smad-2 relative to Smad-2 at a dose-dependent manner^[4]. In C57BL/6J mice, oral administration of tamibarotene (5 mg/kg, once per day) for 4 days prevented intracerebral hemorrhage-induced neuron loss compared to vehicle-treated group. The same treatment also decreased the number of activated microglia/macrophages and the expression of HO-1 associated with intracerebral hemorrhage^[5].
• 细胞研究
• Cell Data

  Cell Lines	Concentration	Assay Type	Time	Activity Description	Data Sources
  COS-1 cells	-	Function assay	-	Transcriptional activation in COS-1 cells expressing Retinoic Acid Receptor alpha (RAR alpha)	10669568
  HL60 cells	-	Proliferation assay	-	Antiproliferative activity against human HL60 cells, IC50=6 μM	19443225
  HL60 cells	-	Proliferation assay	48 h	Antiproliferative activity against human HL60 cells after 48 hrs by MTT assay, IC50=8.94 μM	22014829

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• 动物研究
  剂量	Mice: 2.5 mg/kg[3] (p.o.); 15 mg/kg[4] (i.p.) Rat: 2 mg/kg - 10 mg/kg[5] (p.o.)
  给药途径	p.o., i.p.

• 临床研究

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  NCT01226147	Lupus Nephritis	Phase 2	Unknown	February 2013	Japan ... more >> Kinki University Hospital Recruiting Osaka, Japan, 5898511 Contact: Masanori Funauchi, M.D.       mn-funa@med.kindai.ac.jp    Principal Investigator: Masanori Funauchi, M.D. Collapse <<

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• 参考文献

• [1] Uruno A, Noguchi N, et al. All-trans retinoic acid and a novel synthetic retinoid tamibarotene (Am80) differentially regulate CD38 expression in human leukemia HL-60 cells: possible involvement of protein kinase C-delta. J Leukoc Biol. 2011 Aug;90(2):235-47.

  [2] Sanda T, Kuwano T, et al. Antimyeloma effects of a novel synthetic retinoid Am80 (Tamibarotene) through inhibition of angiogenesis. Leukemia. 2005 Jun;19(6):901-9.

  [3] Bernard BA, Bernardon JM, Delescluse C, Martin B, Lenoir MC, Maignan J, Charpentier B, Pilgrim WR, Reichert U, Shroot B. Identification of synthetic retinoids with selectivity for human nuclear retinoic acid receptor gamma. Biochem Biophys Res Commun. 1992 Jul 31;186(2):977-83.

  [4] Jimi S, Mashima K, Matsumoto T, Hara S, Suzumiya J, Tamura K. RARalpha is a regulatory factor for Am-80-induced cell growth inhibition of hematologic malignant cells. Int J Oncol. 2007 Aug;31(2):397-404.

  [5] Matsushita H, Hijioka M, Hisatsune A, Isohama Y, Shudo K, Katsuki H. A retinoic acid receptor agonist Am80 rescues neurons, attenuates inflammatory reactions, and improves behavioral recovery after intracerebral hemorrhage in mice. J Cereb Blood Flow Metab. 2011 Jan;31(1):222-34.

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