You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on DrugBank.
Identification
NameTamibarotene
Accession NumberDB04942
Typesmall molecule
Groupsapproved, investigational
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
Synonyms
SynonymLanguageCode
Am 80Not AvailableNot Available
retinobenzoic acidNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
AmnoidNot Available
TamibaroNot Available
Brand mixturesNot Available
Categories
CAS number94497-51-5
WeightAverage: 351.4388
Monoisotopic: 351.183443671
Chemical FormulaC22H25NO3
InChI KeyMUTNCGKQJGXKEM-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)
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
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassBenzenoids
ClassTetralins
SubclassNot Available
Direct parentTetralins
Alternative parentsAnilides; Benzamides; Benzoic Acids; Benzoyl Derivatives; Secondary Carboxylic Acid Amides; Enolates; Polyamines; Carboxylic Acids
Substituentsbenzoyl; benzene; carboxamide group; secondary carboxylic acid amide; carboxylic acid derivative; enolate; carboxylic acid; polyamine; amine; organonitrogen compound
Classification descriptionThis compound belongs to the tetralins. These are polycyclic aromatic compounds containing a tetralin moiety, which consists of a benzene fused to a cyclohexane.
Pharmacology
IndicationInvestigated for use/treatment in leukemia (unspecified).
PharmacodynamicsTamibarotene 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 actionTamibarotene is a specific agonist for retinoic acid receptor alpha/beta with possible binding to retinoid X receptors (RXR).
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingOver 99%, predominantly to serum albumin.
Metabolism
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9674
Blood Brain Barrier + 0.9589
Caco-2 permeable + 0.5697
P-glycoprotein substrate Non-substrate 0.5279
P-glycoprotein inhibitor I Non-inhibitor 0.8669
P-glycoprotein inhibitor II Non-inhibitor 0.7046
Renal organic cation transporter Non-inhibitor 0.944
CYP450 2C9 substrate Non-substrate 0.7094
CYP450 2D6 substrate Non-substrate 0.8324
CYP450 3A4 substrate Substrate 0.6002
CYP450 1A2 substrate Inhibitor 0.9107
CYP450 2C9 substrate Non-inhibitor 0.7524
CYP450 2D6 substrate Non-inhibitor 0.9231
CYP450 2C19 substrate Non-inhibitor 0.6225
CYP450 3A4 substrate Non-inhibitor 0.925
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.7513
Ames test Non AMES toxic 0.8459
Carcinogenicity Non-carcinogens 0.7487
Biodegradation Not ready biodegradable 0.9496
Rat acute toxicity 2.1477 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9979
hERG inhibition (predictor II) Non-inhibitor 0.9012
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
Statesolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
water solubility5.75e-04 g/lALOGPS
logP4.99ALOGPS
logP5.35ChemAxon
logS-5.8ALOGPS
pKa (strongest acidic)3.69ChemAxon
pKa (strongest basic)-4ChemAxon
physiological charge-1ChemAxon
hydrogen acceptor count3ChemAxon
hydrogen donor count2ChemAxon
polar surface area66.4ChemAxon
rotatable bond count3ChemAxon
refractivity104.38ChemAxon
polarizability39.16ChemAxon
number of rings3ChemAxon
bioavailability1ChemAxon
rule of fiveNoChemAxon
Ghose filterYesChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

Hisao Ekimoto, “TAMIBAROTENE CAPSULE PREPARATION.” U.S. Patent US20100048708, issued February 25, 2010.

US20100048708
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
ResourceLink
KEGG DrugD01418
KEGG CompoundC12864
PubChem Compound108143
PubChem Substance46509039
ChemSpider97231
ChEBI32181
ChEMBLCHEMBL25202
Therapeutic Targets DatabaseDAP000461
PharmGKBPA164743464
IUPHAR2648
Guide to Pharmacology2648
WikipediaTamibarotene
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

1. Retinoic acid receptor alpha

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

Name UniProt ID Details
Retinoic acid receptor alpha P10276 Details

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

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

Name UniProt ID Details
Retinoic acid receptor beta P10826 Details

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
comments powered by Disqus
Drug created on October 21, 2007 16:23 / Updated on September 16, 2013 17:26