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Identification
Name Tamibarotene
Accession Number DB04942
Type small molecule
Groups approved
Description

Tamibarotene is a novel synthetic retinoid for acute promyelocytic leukaemia (APL). Tamibarotene is currently approved in Japan for treatment of recurrent APL, and is undergoing clinical trials in the United States.
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
Am 80
retinobenzoic acid
Salts Not Available
Brand names
Name Company
Amnoid
Tamibaro
Brand mixtures Not Available
Categories
  • Anticancer Agents
CAS number 94497-51-5
Weight Average: 351.4388
Monoisotopic: 351.183443671
Chemical Formula C22H25NO3
InChI Key InChIKey=MUTNCGKQJGXKEM-UHFFFAOYSA-N
InChI
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)
Plain Text
IUPAC Name
4-[(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)carbamoyl]benzoic acid
SMILES
CC1(C)CCC(C)(C)C2=C1C=CC(NC(=O)C1=CC=C(C=C1)C(O)=O)=C2
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Naphthalenes
  • Benzoates
  • Benzamides
Substructures
  • Hydroxy Compounds
  • Benzyl Alcohols and Derivatives
  • Naphthalenes
  • Acetates
  • Benzoates
  • Amino Ketones
  • Benzene and Derivatives
  • Carboxylic Acids and Derivatives
  • Aromatic compounds
  • Carboxamides and Derivatives
  • Benzoyl Derivatives
  • Cyclohexenes and Derivatives
  • Benzamides
  • Anilines
Pharmacology
Indication Investigated for use/treatment in leukemia (unspecified).
Pharmacodynamics Tamibarotene is a new synthetic retinoid drug recently approved for relapsed or refractory acute promyelocytic leukemia (APL) in Japan. It is a specific agonist for retinoic acid receptor alpha/beta. Compared to all-trans retinoic acid (ATRA), a natural retinoid indicated for a first-line treatment of APL, tamibarotene is chemically more stable and several times more potent as an inducer of differentiation in promyelocytic leukemia cells. In contrast to ATRA, whose plasma concentration declines considerably during daily administration, tamibarotene sustains plasma level probably due to a lower affinity for cellular retinoic acid binding protein. Furthermore, adverse side effects were milder than those of ATRA in clinical trials.
Mechanism of action Tamibarotene is a specific agonist for retinoic acid receptor alpha/beta with possible binding to retinoid X receptors (RXR).
Absorption Not Available
Volume of distribution Not Available
Protein binding Over 99%, predominantly to serum albumin.
Metabolism Not Available
Route of elimination Not Available
Half life Not Available
Clearance Not Available
Toxicity Not Available
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers Not Available
Packagers Not Available
Dosage forms Not Available
Prices Not Available
Patents Not Available
Properties
State solid
Experimental Properties Not Available
Predicted Properties
Property Value Source
water solubility 5.75e-04 g/l ALOGPS
logP 4.99 ALOGPS
logP 5.35 ChemAxon
logS -5.8 ALOGPS
pKa (strongest acidic) 3.69 ChemAxon
pKa (strongest basic) -4 ChemAxon
physiological charge -1 ChemAxon
hydrogen acceptor count 3 ChemAxon
hydrogen donor count 2 ChemAxon
polar surface area 66.4 ChemAxon
rotatable bond count 3 ChemAxon
refractivity 104.38 ChemAxon
polarizability 39.16 ChemAxon
References
Synthesis Reference Not Available
General Reference
  1. Miwako I, Kagechika H: Tamibarotene. Drugs Today (Barc). 2007 Aug;43(8):563-8. Pubmed
  2. Tamibarotene: AM 80, retinobenzoic acid, Tamibaro. Drugs R D. 2004;5(6):359-62. Pubmed
  3. 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
  4. Takeuchi M: [Clinical experience with a new synthetic retinoid, tamibarotene (Am-80) for relapsed or refractory acute promyelocytic leukemia] Gan To Kagaku Ryoho. 2006 Mar;33(3):397-401. Pubmed
  5. Mizojiri K, Okabe H, Sugeno K, Misaki A, Ito M, Kominami G, Esumi Y, Takaichi M, Harada T, Seki H, Inaba A: Studies on the metabolism and disposition of the new retinoid 4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)carbamoyl] benzoic acid. 4th communication: absorption, metabolism, excretion and plasma protein binding in various animals and man. Arzneimittelforschung. 1997 Mar;47(3):259-69. Pubmed
External Links
Resource Link
KEGG Drug D01418 Link_out
KEGG Compound C12864 Link_out
PubChem Compound 108143 Link_out
PubChem Substance 46509039 Link_out
ChemSpider 97231 Link_out
ChEBI 32181 Link_out
ChEMBL 32181 Link_out
Therapeutic Targets Database DAP000461 Link_out
PharmGKB PA164743464 Link_out
IUPHAR 2648 Link_out
Guide to Pharmacology 2648 Link_out
Wikipedia http://en.wikipedia.org/wiki/Tamibarotene Link_out
ATC Codes Not Available
AHFS Codes Not Available
PDB Entries Not Available
FDA label Not Available
MSDS Not Available
Interactions
Drug Interactions Not Available
Food Interactions Not Available
Targets

1. Retinoic acid receptor alpha

Pharmacological action: yes
Actions: agonist

This is a receptor for retinoic acid. This metabolite has profound effects on vertebrate development. Retinoic acid is a morphogen and is a powerful teratogen. This receptor controls cell function by directly regulating gene expression

Organism class: human
UniProt ID: P10276 Link_out
Gene: RARA Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Miwako I, Kagechika H: Tamibarotene. Drugs Today (Barc). 2007 Aug;43(8):563-8. Pubmed
  2. 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
  3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  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. Pubmed
  5. Tamibarotene: AM 80, retinobenzoic acid, Tamibaro. Drugs R D. 2004;5(6):359-62. Pubmed

2. Retinoic acid receptor beta

Pharmacological action: yes
Actions: agonist

This is a receptor for retinoic acid. This metabolite has profound effects on vertebrate development. Retinoic acid is a morphogen and is a powerful teratogen. This receptor controls cell function by directly regulating gene expression

Organism class: human
UniProt ID: P10826 Link_out
Gene: RARB Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Miwako I, Kagechika H: Tamibarotene. Drugs Today (Barc). 2007 Aug;43(8):563-8. Pubmed
  2. 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
  3. 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. Pubmed
  4. Tamibarotene: AM 80, retinobenzoic acid, Tamibaro. Drugs R D. 2004;5(6):359-62. Pubmed
Comments
Drug created on October 21, 2007 16:23 / Updated on February 08, 2013 16:23