WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 202780
CAS#: 94497-51-5
Description: Tamibarotene, also known as SY-1425, 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.
MedKoo Cat#: 202780
Name: Tamibarotene
CAS#: 94497-51-5
Chemical Formula: C22H25NO3
Exact Mass: 351.18344
Molecular Weight: 351.44
Elemental Analysis: C, 75.19; H, 7.17; N, 3.99; O, 13.66
Synonym: Retinobenzoic acid, Amnoid, AMNOLAKE, Am80, Am 80, Am-80; SY-1425; SY 1425; SY1425; Tamibarotene;
IUPAC/Chemical Name: 4-[(5,5,8,8-Tetramethyl-6,7-dihydronaphthalen-2-yl)carbamoyl]benzoic acid
InChi Key: MUTNCGKQJGXKEM-UHFFFAOYSA-N
InChi Code: InChI=1S/C22H25NO3/c1-21(2)11-12-22(3,4)18-13-16(9-10-17(18)21)23-19(24)14-5-7-15(8-6-14)20(25)26/h5-10,13H,11-12H2,1-4H3,(H,23,24)(H,25,26)
SMILES Code: O=C(O)C1=CC=C(C(NC2=CC=C3C(C)(C)CCC(C)(C)C3=C2)=O)C=C1
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
The following data is based on the product molecular weight 351.44 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
1: Kitaoka K, Sano A, Chikahisa S, Yoshizaki K, Séi H. Disturbance of rapid eye movement sleep in senescence-accelerated mouse prone/8 mice is improved by retinoic acid receptor agonist Am80 (Tamibarotene). Neuroscience. 2010 May 19;167(3):573-82. Epub 2010 Feb 4. PubMed PMID: 20138974.
2: Sugitani M, Abe R, Ikarashi N, Ito K, Muratake H, Shudo K, Sugiyama K. Disposition of a new tamibarotene prodrug in mice. Biol Pharm Bull. 2009 Dec;32(12):1997-2001. PubMed PMID: 19952418.
3: Tacke R, Müller V, Büttner MW, Lippert WP, Bertermann R, Daiss JO, Khanwalkar H, Furst A, Gaudon C, Gronemeyer H. Synthesis and pharmacological characterization of Disila-AM80 (Disila-tamibarotene) and Disila-AM580, silicon analogues of the RARalpha-selective retinoid agonists AM80 (Tamibarotene) and AM580. ChemMedChem. 2009 Nov;4(11):1797-802. PubMed PMID: 19790202.
4: Kawahara K, Nishi K, Suenobu M, Ohtsuka H, Maeda A, Nagatomo K, Kuniyasu A, Staufenbiel M, Nakagomi M, Shudo K, Nakayama H. Oral administration of synthetic retinoid Am80 (Tamibarotene) decreases brain beta-amyloid peptides in APP23 mice. Biol Pharm Bull. 2009 Jul;32(7):1307-9. PubMed PMID: 19571405.
5: Fukui T, Kodera Y, Nishio K, Masuda N, Tamura T, Koizumi F. Synergistic interactions between the synthetic retinoid tamibarotene and glucocorticoids in human myeloma cells. Cancer Sci. 2009 Jun;100(6):1137-43. PubMed PMID: 19514122.
6: Nakazato T, Okudaira T, Ishikawa C, Nakama S, Sawada S, Tomita M, Uchihara JN, Taira N, Masuda M, Tanaka Y, Ohshiro K, Takasu N, Mori N. Anti-adult T-cell leukemia effects of a novel synthetic retinoid, Am80 (Tamibarotene). Cancer Sci. 2008 Nov;99(11):2286-94. Epub 2008 Sep 1. PubMed PMID: 18771528.
7: Miwako I, Kagechika H. Tamibarotene. Drugs Today (Barc). 2007 Aug;43(8):563-8. Review. PubMed PMID: 17925887.
8: Sanda T, Kuwano T, Nakao S, Iida S, Ishida T, Komatsu H, Shudo K, Kuwano M, Ono M, Ueda R. Antimyeloma effects of a novel synthetic retinoid Am80 (Tamibarotene) through inhibition of angiogenesis. Leukemia. 2005 Jun;19(6):901-9. PubMed PMID: 15843826.
9: Tamibarotene: AM 80, retinobenzoic acid, Tamibaro. Drugs R D. 2004;5(6):359-62. Review. PubMed PMID: 15563242.
10: Shudo K, Kagechika H, Yamazaki N, Igarashi M, Tateda C. A synthetic retinoid Am80 (tamibarotene) rescues the memory deficit caused by scopolamine in a passive avoidance paradigm. Biol Pharm Bull. 2004 Nov;27(11):1887-9. Erratum in: Biol Pharm Bull. 2005 Dec;28(12):2346. PubMed PMID: 15516744.
Tamibarotene is currently being developed by CytRx Corporation. According to CytRx Corporation's webpages, Tamibarotene was developed to specifically overcome resistance to ATRA. In vitro, tamibarotene is approximately 10 times more potent than ATRA at causing APL cells to differentiate and die. In addition, tamibarotene has a lower affinity for cellular retinoic acid binding protein, or CRABP, which we believe should allow for sustained plasma levels during administration. Tamibarotene does not bind the RAR-α receptor, the major retinoic acid receptor in the dermal epithelium. In clinical studies, the rate of RAS appeared to be low.
Tamibarotene is currently approved in Japan for treatment of recurrent APL. There is a Special Protocol Assessment (SPA) in place with the FDA for a Phase 2 clinical trial, known as STAR-1, which is evaluating the efficacy and safety of tamibarotene as a third-line treatment for APL. The STAR-1 trial is ongoing and currently includes six clinical sites in the U.S. CytRx recently reported that, of the 11 patients enrolled in the STAR-1 trial to date, three (27%) achieved a hematologic complete response, and four (36%) a morphologic leukemia-free state. Based on the preliminary results in the clinical trial for third-line APL, CytRx has announced its intention to work with key opinion leaders to design a clinical trial to evaluate tamibarotene in combination with other agents as a first-line treatment for this cancer. CytRx holds the North American and European rights to tamibarotene as a treatment for APL. The FDA has granted Orphan Drug Designation for APL and Fast Track Designation for the use of tamibarotene in patients with relapsed or refractory APL following treatment with all-trans retinoic acid (ATRA) and arsenic trioxide. In addition, tamibarotene has been granted orphan medicinal product status by the European Medicines Agency for the treatment of APL. The efficacy of orally-administered tamibarotene was demonstrated in two Phase 2 studies conducted in Japan in a total of 63 Japanese subjects with APL. The overall complete response rate in these subjects was 60%. In subjects experiencing their first relapse, the overall complete response rate was 81%.
