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Purity: ≥98%
Tamibarotene (formerly SY-1425; SY1425; Am 80; Retinobenzoic acid, Amnoid, AMNOLAKE) is a novel, potent, orally bioavailable, and synthetic retinoic acid receptor (RAR) agonist with potential anticancer activity against AML-acute promyelocytic leukaemia. It has high specificity for RARα and RARβ over RARγ. Tamibarotene is developed to overcome all-trans retinoic acid (ATRA) resistance. As a specific retinoic acid receptor (RAR) alpha/beta agonist, tamibarotene is approximately ten times more potent than ATRA in inducing cell differentiation and apoptosis in HL-60 (human promyelocytic leukemia) cell lines in vitro.
| ln Vitro |
In T-cell lymphoma cells, tamibarotene (20, 40 μM) suppresses the expression of genes related to the cell cycle. When tamibarotene (5 μM) is added to RARA-overexpressing cells, it significantly boosts RARE activity compared to RARAlow cells. Moreover, treatment with tamibarotene enhances the degree of CDK2, CDK4, and CDK6 inhibition due to RARAwt overexpression [1]. Tamibarotene directly counteracts the profibrotic phenotype of dermal fibroblasts treated with transforming growth factor-β1, suppresses ICAM-1 expression in endothelial cells, and stimulates the development of M1 macrophages in vitro [2]. In VSMC, tamibarotene (4 μM) dose-dependently increases apelin mRNA and protein levels. As a result of interacting with KLF5 and Sp1, which are pre-bound to the apelin promoter's TCE site, RARα (retinoic acid receptor α) is recruited to the apelin promoter during tamibarotene stimulation. This transcriptional activation complex then triggers apelin expression. elevated in the VSMC. By directly binding to TCE on the apelin promoter, KLF5 and Sp1 work together to mediate the expression of apelin induced by tamibarotene [4].
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| ln Vivo |
In mice treated with bleomycin (BLM) and skin-tightening 1 mice, tamibarotene (1 mg/kg/day) significantly decreased dermal and subdermal fibrosis, respectively. Tamibarotene consistently and significantly inhibits the expression of several molecules linked to tissue fibrosis in the lesional skin of BLM-treated mice, including transforming growth factor-β1, connective tissue growth factor, IL-4, IL-10, IL-13, IL-17A, tumor necrosis factor-α, IFN-γ, and monocyte chemoattractant protein 1. Furthermore, in the draining lymph nodes of mice treated with BLM, tamibarotene increased the proportion of naive T cells and decreased the proportion of effector T cells among CD4+ T cells [2]. When compared to mice not receiving treatment, mice with periodontitis did not exhibit any appreciable changes in serum levels of AST, ALT, or ALP when given tamibarotene (2.5 mg/kg, po). Tamibarotene decreases the quantity of P. gingivalis-induced mouse osteoclasts and enhances alveolar bone resorption. When compared to EPD mice, tamibarotene significantly raised the percentage of CD4+ Foxp3+ Treg cells. Additionally, tamibarotene successfully lowers the expression of Th17 (CD4+ROR-γt+) cells in P. CLNs and gingival tissue were infected by gingivalis[3]. Rats with balloon-injured arteries express more apelin when given tamibarotene (1 mg/kg, po), which is in line with findings from cultured VSMCs [4]. The hippocampal ADAM10 levels in aged SAMP8 mice showed an improvement following the administration of Tamibarotene (1 mg/kg/day). After taking tamibarotene, Hes5 and Ki67 were recovered, and spatial working memory was enhanced [5].
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| References |
[1]. Wang X, et al. Retinoic acid receptor alpha drives cell cycle progression and is associated with increased sensitivity to retinoids in T-cell lymphoma. Oncotarget. 2017 Apr 18;8(16):26245-26255.
[2]. Toyama T, et al. Tamibarotene Ameliorates Bleomycin-Induced Dermal Fibrosis by Modulating Phenotypes of Fibroblasts, Endothelial Cells, and Immune Cells. J Invest Dermatol. 2016 Feb;136(2):387-98. [3]. Jin Y, et al. Tamibarotene modulates the local immune response in experimental periodontitis. Int Immunopharmacol. 2014 Dec;23(2):537-45. [4]. Lv XR, et al. Synthetic retinoid Am80 up-regulates apelin expression by promoting interaction of RARα with KLF5 and Sp1 in vascular smooth muscle cells. Biochem J. 2013 Nov 15;456(1):35-46. [5]. Kitaoka K, et al. The retinoic acid receptor agonist Am80 increases hippocampal ADAM10 in aged SAMP8 mice. Neuropharmacology. 2013 Sep;72:58-65 |
| Molecular Formula |
C22H25NO3
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| Molecular Weight |
351.44
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| CAS # |
94497-51-5
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| SMILES |
O=C(O)C1=CC=C(C(NC2=CC=C3C(C)(C)CCC(C)(C)C3=C2)=O)C=C1
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.11 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (7.11 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (7.11 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.8454 mL | 14.2272 mL | 28.4544 mL | |
| 5 mM | 0.5691 mL | 2.8454 mL | 5.6909 mL | |
| 10 mM | 0.2845 mL | 1.4227 mL | 2.8454 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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