Tamibarotene | CAS#94497-51-5 | Retinoid

MedKoo Cat#: 202780 | Name: Tamibarotene

Description:

WARNING: This product is for research use only, not for human or veterinary use.

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.

Chemical Structure

Tamibarotene

CAS#94497-51-5

Theoretical Analysis

MedKoo Cat#: 202780

Name: Tamibarotene

CAS#: 94497-51-5

Chemical Formula: C22H25NO3

Exact Mass: 351.1834

Molecular Weight: 351.44

Elemental Analysis: C, 75.19; H, 7.17; N, 3.99; O, 13.66

Price and Availability

Size	Price	Availability
200mg	USD 150.00	Ready to ship
500mg	USD 330.00	Ready to ship
1g	USD 580.00	Ready to ship
2g	USD 950.00	Ready to ship
5g	USD 1,950.00	Ready to ship
10g	USD 3,250.00	Ready to ship
20g	USD 5,450.00	Ready to ship

Bulk Inquiry

Buy Now

Add to Cart

Related CAS #

No Data

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

More Info

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%.

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#C20R08B10

QC Data

View QC data: current batch, Lot#C20R08B10

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Tamibarotene is a retinoic acid receptor α/β (RARα/β) agonist, showing high selectivity over RARγ.

In vitro activity:

To further investigate the effect of Am80 on apelin promoter activity, VSMCs were co-transfected with GFP–KLF5 expression plasmids and apelin promoter–reporter constructs containing various 5′-deletion fragments. As shown in Figure 4(C), KLF5 overexpression significantly elevated the activities of the apelin promoter of the three different constructs. When Am80 was added, the relative activity of the different constructs further increased. To assess whether the TCE sites in the apelin promoter region were required for Am80-induced apelin expression, the promoter constructs in which the different TCE sites were mutated were co-transfected, respectively, with KLF5 expression plasmid GFP–KLF5. The luciferase activity assay results showed that mutation of site-2 or site-3 did not affect apelin promoter activity and that only the mutation of site-1 blocked the activation of the apelin promoter by KLF5 (Figure 4D). To investigate whether KLF5 bound directly to the TCE sites in Am80-stimulated VSMCs, an oligonucleotide pull-down assay was carried out. As shown in Figure 4(E), KLF5 was bound only to TCE site-1 of the apelin promoter, and Am80 treatment increased its binding. Furthermore, no KLF5 bands were detected when probes containing site-2 or site-3 were used. These results suggest that KLF5 activated apelin transcription by directly binding to site-1 of the apelin promoter. Reference: Biochem J. 2013 Nov 15;456(1):35-46. https://portlandpress.com/biochemj/article-lookup/doi/10.1042/BJ20130418

In vivo activity:

Dermal thickness of lesional skin sections was greater in BLM-treated mice than in phosphate-buffered saline (PBS)-treated mice on day 28 but was comparable on day 7. Of note, Am80 significantly attenuated BLM-induced dermal thickness on day 28 (Figure 1a). Consistent with this finding, Am80 treatment significantly reduced collagen content and mRNA expression of the Col1a1, Col1a2, Col3a1, and Col5a1 genes while promoting that of the Mmp13 gene in the lesional skin of BLM-treated mice (Figure 1b and c). Becasue transforming growth factor (TGF)-β1 and connective tissue growth factor (CTGF) are enough to induce experimental dermal fibrosis and their elevated expression is the hallmark of SSc dermal fibroblasts, the expression of these growth factors was examined. As expected, the decrease in mRNA expression of the Tgfb1 and Ctgf genes was noted in BLM-treated mice exposed to Am80 (Figure 1d), which was also confirmed at protein levels by immunohistochemistry (Figure 1e). To further elucidate the antifibrotic effect of Am80 on tissue fibrosis, TSK1 mice were employed, another widely accepted murine SSc model characterized by increased hypodermal thickness. In line with the results of BLM-treated mice, Am80 significantly ameliorated hypodermal thickness and collagen content in the back skin of TSK1 mice (Figure 1f and g). These findings suggest that Am80 exerts a potent antifibrotic effect on dermal fibrosis by reducing the production of collagen, promoting its degradation, and regulating expression of various soluble factors in SSc murine models. Reference: J Invest Dermatol. 2016 Feb;136(2):387-398. https://linkinghub.elsevier.com/retrieve/pii/S0022-202X(15)00059-7

	Solvent	mg/mL	mM
Solubility
	DMSO	17.6	50.00
	Ethanol	17.6	50.00

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

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

Formulation protocol:

In vitro protocol:

1. Lv XR, Zheng B, Li SY, Han AL, Wang C, Shi JH, Zhang XH, Liu Y, Li YH, Wen JK. 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. doi: 10.1042/BJ20130418. PMID: 23992409. 2. 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. PMID: 25448496.

In vivo protocol:

1. 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):387-398. doi: 10.1016/j.jid.2015.10.058. Epub 2015 Nov 18. PMID: 26967475. 2. Kitaoka K, Shimizu N, Ono K, Chikahisa S, Nakagomi M, Shudo K, Ishimura K, Séi H, Yoshizaki K. The retinoic acid receptor agonist Am80 increases hippocampal ADAM10 in aged SAMP8 mice. Neuropharmacology. 2013 Sep;72:58-65. doi: 10.1016/j.neuropharm.2013.04.009. Epub 2013 Apr 23. PMID: 23624141.

1: Goulding E, Ward L, Allan F, Dittman D, Salcedo-Sora JE, Carnell AJ. Development of the esterase PestE for amide bond synthesis under aqueous conditions: Enzyme cascades for converting waste PET into tamibarotene. Angew Chem Int Ed Engl. 2024 Oct 28:e202414162. doi: 10.1002/anie.202414162. Epub ahead of print. PMID: 39466189. 2: He Z, Dydio P. Photoinduced Cu(II)-Mediated Decarboxylative Thianthrenation of Aryl and Heteroaryl Carboxylic Acids. Angew Chem Int Ed Engl. 2024 Oct 14;63(42):e202410616. doi: 10.1002/anie.202410616. Epub 2024 Sep 5. PMID: 39012681. 3: Li X, Jiang S, Wang B, He S, Guo X, Lin J, Wei Y. Integrated multi-omics analysis and machine learning developed diagnostic markers and prognostic model based on Efferocytosis-associated signatures for septic cardiomyopathy. Clin Immunol. 2024 Aug;265:110301. doi: 10.1016/j.clim.2024.110301. Epub 2024 Jun 27. PMID: 38944364. 4: Peng P, Shen Y. Identification of shared disease marker genes and underlying mechanisms between rheumatoid arthritis and Crohn disease through bioinformatics analysis. Medicine (Baltimore). 2024 Jun 28;103(26):e38690. doi: 10.1097/MD.0000000000038690. PMID: 38941374; PMCID: PMC11466148. 5: Owaki T, Iida T, Miyai Y, Kato K, Hase T, Ishii M, Ando R, Hinohara K, Akashi T, Mizutani Y, Ishikawa T, Mii S, Shiraki Y, Esaki N, Yamamoto M, Tsukamoto T, Nomura S, Murakami T, Takahashi M, Yuguchi Y, Maeda M, Sano T, Sassa N, Matsukawa Y, Kawashima H, Akamatsu S, Enomoto A. Synthetic retinoid-mediated preconditioning of cancer-associated fibroblasts and macrophages improves cancer response to immune checkpoint blockade. Br J Cancer. 2024 Jul;131(2):372-386. doi: 10.1038/s41416-024-02734-3. Epub 2024 Jun 7. PMID: 38849479; PMCID: PMC11263587. 6: Fleischmann M, Bechwar J, Voigtländer D, Fischer M, Schnetzke U, Hochhaus A, Scholl S. Synergistic Effects of the RARalpha Agonist Tamibarotene and the Menin Inhibitor Revumenib in Acute Myeloid Leukemia Cells with KMT2A Rearrangement or NPM1 Mutation. Cancers (Basel). 2024 Mar 28;16(7):1311. doi: 10.3390/cancers16071311. PMID: 38610989; PMCID: PMC11011083. 7: Alsharief M. How Do Retinoids Affect Alzheimer's Disease and Can They Be Novel Drug Candidates? Cureus. 2024 Apr 3;16(4):e57548. doi: 10.7759/cureus.57548. PMID: 38572181; PMCID: PMC10990449. 8: Sekiguchi Y, Tsutsumi H, Gomyo A, Kudo M, Maseki N, Iizaki Y, Kawamura M, Kobayashi K, Nitta H, Noguchi M, Wakita S, Yamaguchi H, Kobayashi H. A Case of Relapsed/Refractory CD56-Positive Acute Promyelocytic Leukemia, in Which Complete Molecular Remission Was Achieved Following Combination Therapy with Venetoclax and Azacitidine. Gan To Kagaku Ryoho. 2024 Mar;51(3):291-297. PMID: 38494811. 9: Liang S, Zheng YY, Pan Y. Blood transcriptome analysis uncovered COVID-19-myocarditis crosstalk. Microb Pathog. 2024 Apr;189:106587. doi: 10.1016/j.micpath.2024.106587. Epub 2024 Feb 17. PMID: 38373644. 10: Makimoto A, Fujisaki H, Matsumoto K, Takahashi Y, Cho Y, Morikawa Y, Yuza Y, Tajiri T, Iehara T. Retinoid Therapy for Neuroblastoma: Historical Overview, Regulatory Challenges, and Prospects. Cancers (Basel). 2024 Jan 26;16(3):544. doi: 10.3390/cancers16030544. PMID: 38339295; PMCID: PMC10854948. 11: Ji S, Li Y, Xiang L, Liu M, Xiong M, Cui W, Fu X, Sun X. Cocktail Cell- Reprogrammed Hydrogel Microspheres Achieving Scarless Hair Follicle Regeneration. Adv Sci (Weinh). 2024 Mar;11(12):e2306305. doi: 10.1002/advs.202306305. Epub 2024 Jan 15. PMID: 38225741; PMCID: PMC10966561. 12: Stein EM, de Botton S, Cluzeau T, Pigneux A, Liesveld JL, Cook RJ, Rousselot P, Rizzieri DA, Braun T, Roboz GJ, Lebon D, Heiblig M, Baker K, Volkert A, Paul S, Rajagopal N, Roth DA, Kelly M, Peterlin P. Use of tamibarotene, a potent and selective RARα agonist, in combination with azacitidine in patients with relapsed and refractory AML with RARA gene overexpression. Leuk Lymphoma. 2023 Dec;64(12):1992-2001. doi: 10.1080/10428194.2023.2243356. Epub 2023 Aug 12. PMID: 37571998. 13: Nagai Y, Ambinder AJ. The Promise of Retinoids in the Treatment of Cancer: Neither Burnt Out Nor Fading Away. Cancers (Basel). 2023 Jul 8;15(14):3535. doi: 10.3390/cancers15143535. PMID: 37509198; PMCID: PMC10377082. 14: Kasamoto M, Funakoshi S, Hatani T, Okubo C, Nishi Y, Tsujisaka Y, Nishikawa M, Narita M, Ohta A, Kimura T, Yoshida Y. Am80, a retinoic acid receptor agonist, activates the cardiomyocyte cell cycle and enhances engraftment in the heart. Stem Cell Reports. 2023 Aug 8;18(8):1672-1685. doi: 10.1016/j.stemcr.2023.06.006. Epub 2023 Jul 13. PMID: 37451261; PMCID: PMC10444569. 15: Xu C, Li J. Tamibarotene targets heparin-binding protein for attenuating lung injury in sepsis. Allergol Immunopathol (Madr). 2023 Jul 1;51(4):124-130. doi: 10.15586/aei.v51i4.900. PMID: 37422788. 16: Nakanishi S, Kinoshita K, Kurauchi Y, Seki T, Kimura Y, Suzuki M, Suzuki K, Koyama H, Kagechika H, Katsuki H. Acyclic retinoid peretinoin reduces hemorrhage-associated brain injury in vitro and in vivo. Eur J Pharmacol. 2023 Sep 5;954:175899. doi: 10.1016/j.ejphar.2023.175899. Epub 2023 Jun 29. PMID: 37392831. 17: Akita T, Oda K, Narukawa S, Morita Y, Tange K, Nakai Y, Yamashita C. Intracellular Drug Delivery Process of Am80-Encapsulated Lipid Nanoparticles Aiming for Alveolar Regeneration. Pharmaceuticals (Basel). 2023 Jun 4;16(6):838. doi: 10.3390/ph16060838. PMID: 37375785; PMCID: PMC10304494. 18: Singh DK, Carcamo S, Farias EF, Hasson D, Zheng W, Sun D, Huang X, Cheung J, Nobre AR, Kale N, Sosa MS, Bernstein E, Aguirre-Ghiso JA. 5-Azacytidine- and retinoic-acid-induced reprogramming of DCCs into dormancy suppresses metastasis via restored TGF-β-SMAD4 signaling. Cell Rep. 2023 Jun 27;42(6):112560. doi: 10.1016/j.celrep.2023.112560. Epub 2023 Jun 1. PMID: 37267946; PMCID: PMC10592471. 19: Wu X, Jiao Z, Zhang J, Li F, Li Y. Expression of TFRC helps to improve the antineoplastic effect of Ara-C on AML cells through a targeted delivery carrier. J Nanobiotechnology. 2023 Apr 11;21(1):126. doi: 10.1186/s12951-023-01881-8. PMID: 37041636; PMCID: PMC10088114. 20: Dumas PY, Pigneux A. Prise en charge des LAM chez les sujets âgés [Management of AML in the elderly]. Bull Cancer. 2023 Apr;110(4):424-432. French. doi: 10.1016/j.bulcan.2023.02.005. Epub 2023 Mar 2. PMID: 36870810.