TAMIBAROTENE

Possibly Marketed Outside US

Details

Stereochemistry	ACHIRAL
Molecular Formula	C22H25NO3
Molecular Weight	351.4388
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

SMILES

CC1(C)CCC(C)(C)C2=C1C=CC(NC(=O)C3=CC=C(C=C3)C(O)=O)=C2

InChI

InChIKey=MUTNCGKQJGXKEM-UHFFFAOYSA-N

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)

HIDE SMILES / InChI

Molecular Formula	C22H25NO3
Molecular Weight	351.4388
Charge	0
Count	MOL RATIO 1 MOL RATIO (average)

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description

Tamibarotene (brand name: Amnolake), also called retinobenzoic acid, is orally active, the synthetic retinoid, developed to overcome all-trans retinoic acid (ATRA) resistance, with potential antineoplastic activity against acute promyelocytic leukemia (APL). Tamibarotene is a specific agonist for retinoic acid receptor alpha/beta. 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.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Retinoic acid receptor alpha 11	Agonist 2,678	45.0 nM [EC50]
Retinoic acid receptor beta 18	Agonist 2,678	235.0 nM [EC50]
Retinoic acid receptor gamma 18	Agonist 2,678	591.0 nM [EC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Acute promyelocytic leukemia 13	Primary		Approved 8,429	Amnolake
Graft-versus-host disease 3	Primary		Phase II 1,132	Amnolake

C_max

Value	Dose	Analyte	Population
18.02 ng/mL	2 mg single, oral	TAMIBAROTENE plasma	Homo sapiens
44.87 ng/mL	4 mg single, oral	TAMIBAROTENE plasma	Homo sapiens
65.22 ng/mL	6 mg single, oral	TAMIBAROTENE plasma	Homo sapiens
63.1 ng/mL	6 mg/m² single, oral	TAMIBAROTENE plasma	Homo sapiens
104.4 ng/mL	8 mg/m² single, oral	TAMIBAROTENE plasma	Homo sapiens
126.3 ng/mL	10 mg/m² single, oral	TAMIBAROTENE plasma	Homo sapiens
131.9 ng/mL	12 mg/m² single, oral	TAMIBAROTENE plasma	Homo sapiens
43.2 ng/mL	4 mg single, oral	TAMIBAROTENE plasma	Homo sapiens
97.1 ng/mL	6 mg single, oral	TAMIBAROTENE plasma	Homo sapiens

AUC

Value	Dose	Analyte	Population
128.37 ng × h/mL	2 mg single, oral	TAMIBAROTENE plasma	Homo sapiens
320.41 ng × h/mL	4 mg single, oral	TAMIBAROTENE plasma	Homo sapiens
430.26 ng × h/mL	6 mg single, oral	TAMIBAROTENE plasma	Homo sapiens
311.1 ng × h/mL	6 mg/m² single, oral	TAMIBAROTENE plasma	Homo sapiens
438.9 ng × h/mL	8 mg/m² single, oral	TAMIBAROTENE plasma	Homo sapiens
444.2 ng × h/mL	10 mg/m² single, oral	TAMIBAROTENE plasma	Homo sapiens
514.1 ng × h/mL	12 mg/m² single, oral	TAMIBAROTENE plasma	Homo sapiens
312 ng × h/mL	4 mg single, oral	TAMIBAROTENE plasma	Homo sapiens
751 ng × h/mL	6 mg single, oral	TAMIBAROTENE plasma	Homo sapiens

T_1/2

Value	Dose	Analyte	Population
3.4 h	2 mg single, oral	TAMIBAROTENE plasma	Homo sapiens
4.5 h	4 mg single, oral	TAMIBAROTENE plasma	Homo sapiens
4 h	6 mg single, oral	TAMIBAROTENE plasma	Homo sapiens
11.96 h	6 mg/m² single, oral	TAMIBAROTENE plasma	Homo sapiens
2.35 h	8 mg/m² single, oral	TAMIBAROTENE plasma	Homo sapiens
2.49 h	10 mg/m² single, oral	TAMIBAROTENE plasma	Homo sapiens
2.21 h	12 mg/m² single, oral	TAMIBAROTENE plasma	Homo sapiens
3.38 h	4 mg single, oral	TAMIBAROTENE plasma	Homo sapiens
3.38 h	6 mg single, oral	TAMIBAROTENE plasma	Homo sapiens

F_unbound

Value	Dose	Co-administered	Analyte	Population
0.6%			TAMIBAROTENE plasma	Homo sapiens

Doses

Show entries

Dose	Population	Adverse events
6 mg/m2 1 times / day multiple, oral Studied dose	unhealthy, ADULT	Disc. AE: abnormal coagulation...
12 mg/m2 2 times / day multiple, oral Highest studied dose	unhealthy, CHILD	Other AEs: hyperglyceridemi...

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AEs

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AE	Significance	Dose	Population
abnormal coagulation	Disc. AE	6 mg/m2 1 times / day multiple, oral Studied dose	unhealthy, ADULT
hyperglyceridemi		12 mg/m2 2 times / day multiple, oral Highest studied dose	unhealthy, CHILD

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PubMed

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Title	Date	PubMed
Retinobenzoic acids. 1. Structure-activity relationships of aromatic amides with retinoidal activity.	1988 Nov	3184125
The prevention of adipose differentiation of 3T3-L1 cells caused by retinoic acid is elicited through retinoic acid receptor alpha.	1994	7934625
Activation of retinoid X receptors induces apoptosis in HL-60 cell lines.	1995 Jul	7791761
Re-induction of complete remission with a new synthetic retinoid, Am-80, for relapse of acute promyelocytic leukaemia previously treated with all-trans retinoic acid.	1997 Apr	9136955
Action mechanism of retinoid-synergistic dibenzodiazepines.	1997 Apr 7	9144408

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Patents

Sample Use Guides

In Vivo Use Guide

Tamibarotene 6 mg/m2/day oral dose for a maximum of 56 days

Route of Administration: Oral

In Vitro Use Guide

The cell viability of A549 or MRC-5 cell lines treated with Am80 or ATRA was assessed using the CellTiter-Glo Luminescent Cell Viability Assay (Promega KK, Tokyo, Japan). Cells were seeded at 625 per cm2 in 100 μL of medium in 96-welled flat-bottom plates and grown overnight at 37°C in an incubator. After exposure to Am80 for 6 d, the plates were assayed using EnVision Plate Reader (PerkinElmer, Inc. Japan Co., Ltd., Kanagawa, Japan).

Substance Class	Chemical
Record UNII	08V52GZ3H9
Record Status	`Validated (UNII)`
Record Version

Show entries

Name

Type

Language

TAMIBAROTENE

Official Name

English

AM80

Code

English

TAMIBAROTENE [JAN]

Common Name

English

RR-110

Code

English

OP-01

Code

English

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Classification Tree

Code System

Code

Differentiation Inducer

NCI_THESAURUS

C804

Designated

FDA ORPHAN DRUG

247007

Designated

FDA ORPHAN DRUG

596017

Withdrawn

EU-Orphan Drug

EU/3/09/658

Designated

FDA ORPHAN DRUG

861221

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Code System

Code

Type

Description

CHEBI

32181

PRIMARY

IUPHAR

2648

PRIMARY

NSC

608000

PRIMARY

NCI_THESAURUS

C71025

PRIMARY

USAN

JK-51

PRIMARY

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Related Record

Type

Details


					M1D5A2L709

RETINOIC ACID RECEPTOR ALPHA

TARGET -> AGONIST

Amount:

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Related Record

Type

Details


					08V52GZ3H9

TAMIBAROTENE

ACTIVE MOIETY

Amount:

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SMILES

InChI

CNS Activity

Originator

Approval Year

Targets

Conditions

Cmax

AUC

T1/2

Funbound

Doses

AEs

PubMed

Patents

Sample Use Guides

C_max

T_1/2

F_unbound