Tamibarotene

• CAT Number: A000165
• CAS Number: 94497-51-5
• Molecular Formula: C22H25NO3
• Molecular Weight: 351.4
• Purity: ≥95%
• Target: RARs
• Solubility: >13.4mg/mL in DMSO
• Storage: Store at -20°C
• InChIKey: MUTNCGKQJGXKEM-UHFFFAOYSA-N

Tamibarotene is an orally active, synthetic retinoid, developed to overcome all-trans retinoic acid (ATRA) resistance, with potential antineoplastic activity. 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. Due to a lower affinity for cellular retinoic acid binding protein (CRABP), tamibarotene may show sustained plasma levels compared to ATRA.

Tamibarotene (brand name: Amnolake), also called retinobenzoic acid, is orally active, synthetic retinoid, developed to overcome all-trans retinoic acid (ATRA) resistance, with potential antineoplastic activity against acute promyelocytic leukaemia (APL) . It is currently marketed only in Japan and early trials have demonstrated that it tends to be better tolerated than ATRA. It has also been investigated as a possible treatment for Alzheimer/’s disease, multiple myeloma and Crohn/’s disease.

Reference

1: Tian L, Gao J, Yang Z, Zhang Z, Huang G. Tamibarotene-Loaded PLGA Microspheres
for Intratumoral Injection Administration: Preparation and Evaluation. AAPS
PharmSciTech. 2017 Jul 12. doi: 10.1208/s12249-017-0827-9. [Epub ahead of print]
PubMed PMID: 28702817.

2: Maeda Y, Nishimori H, Inamoto Y, Nakamae H, Sawa M, Mori Y, Ohashi K, Fujiwara
SI, Tanimoto M. An Open-labeled, Multicenter Phase II Study of Tamibarotene in
Patients with Steroid-refractory Chronic Graft-versus-Host Disease. Acta Med
Okayama. 2016 Oct;70(5):409-412. PubMed PMID: 27777437.

3: Kojima M, Ogiya D, Ichiki A, Hara R, Amaki J, Kawai H, Numata H, Sato A,
Miyamoto M, Suzuki R, Machida S, Matsushita H, Ogawa Y, Kawada H, Ando K.
Refractory acute promyelocytic leukemia successfully treated with combination
therapy of arsenic trioxide and tamibarotene: A case report. Leuk Res Rep. 2016
Jan 22;5:11-3. doi: 10.1016/j.lrr.2016.01.001. eCollection 2016. PubMed PMID:
27144119; PubMed Central PMCID: PMC4840419.

4: Jiang Y, Li X, Wang X, Wang Z, Zhang J, Wu J, Xu W. Design, synthesis, and
biological characterization of tamibarotene analogs as anticancer agents. Chem
Biol Drug Des. 2016 Oct;88(4):542-55. doi: 10.1111/cbdd.12778. Epub 2016 Jun 1.
PubMed PMID: 27113097.

5: Toyama T, Asano Y, Akamata K, Noda S, Taniguchi T, Takahashi T, Ichimura Y,
Shudo K, Sato S, Kadono T. 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. doi: 10.1016/j.jid.2015.10.058.
Epub 2015 Nov 18. PubMed PMID: 26967475.

6: Sanford D, Lo-Coco F, Sanz MA, Di Bona E, Coutre S, Altman JK, Wetzler M,
Allen SL, Ravandi F, Kantarjian H, Cortes JE. Tamibarotene in patients with acute
promyelocytic leukaemia relapsing after treatment with all-trans retinoic acid
and arsenic trioxide. Br J Haematol. 2015 Nov;171(4):471-7. doi:
10.1111/bjh.13607. Epub 2015 Jul 24. PubMed PMID: 26205361; PubMed Central PMCID:
PMC4770883.

7: Jin Y, Liu D, Fang X, Gao K, Lin X. [Effect of tamibarotene on innate immune
response in the model of Porphyromonas gingivalis induced periodontitis].
Zhonghua Kou Qiang Yi Xue Za Zhi. 2015 Mar;50(3):146-50. Chinese. PubMed PMID:
26081852.

8: Jin Y, Wang L, Liu D, Lin X. Tamibarotene modulates the local immune response
in experimental periodontitis. Int Immunopharmacol. 2014 Dec;23(2):537-45. doi:
10.1016/j.intimp.2014.10.003. Epub 2014 Oct 14. PubMed PMID: 25448496.

9: Shinagawa K, Yanada M, Sakura T, Ueda Y, Sawa M, Miyatake J, Dobashi N, Kojima
M, Hatta Y, Emi N, Tamaki S, Gomyo H, Yamazaki E, Fujimaki K, Asou N, Matsuo K,
Ohtake S, Miyazaki Y, Ohnishi K, Kobayashi Y, Naoe T. Tamibarotene as maintenance
therapy for acute promyelocytic leukemia: results from a randomized controlled
trial. J Clin Oncol. 2014 Nov 20;32(33):3729-35. doi: 10.1200/JCO.2013.53.3570.
Epub 2014 Sep 22. Erratum in: J Clin Oncol. 2015 Jan 10;33(2):228. PubMed PMID:
25245439.

10: Wang XJ, Duan Y, Li ZT, Feng JH, Pan XP, Zhang XR, Shi LH, Zhang T.
Preparation and antitumor activity of a tamibarotene-furoxan derivative. Asian
Pac J Cancer Prev. 2014;15(15):6343-7. PubMed PMID: 25124622.