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Tamibarotene

Tamibarotene structure

CAS No:
94497-51-5
Formula:
C22H25NO3
Chemical Name:
Tamibarotene
Synonyms:
Benzoic acid,4-[[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)amino]carbonyl]-;4-[[(5,6,7,8-Tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)amino]carbonyl]benzoic acid;Am 80;Tamibarotene;Am 80 (pharmaceutical);NSC 608000;Retinoid AM 80;Amnolake;4-[(5,6,7,8-Tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)carbamoyl]benzoic acid;RR 110;SY 1425;Am 80 (RAR agonist);INNO 507;TM 441;TOS 80T;OP 01
Categories:
Biochemical Engineering > Inhibitors

Description

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

Solid

Tamibarotene is a dicarboxylic acid monoamide resulting from the condensation of one of the carboxy groups of terephthalic acid with the amino group of 5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-amine. It has a role as an antineoplastic agent and a retinoic acid receptor alpha/beta agonist. It is a member of tetralins, a retinoid and a dicarboxylic acid monoamide. It derives from a 4-carbamoylbenzoic acid and a terephthalic acid.|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.|Tamibarotene 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. In addition, this agent may exhibit a lower toxicity profile than ATRA, in part, due to the lack of affinity for the RAR-gamma receptor, the major retinoic acid receptor in the dermal epithelium.

Tamibarotene Basic Attributes

Molecular Weight：

351.44

Exact Mass：

351.44

EC Number：

1806241-263-5

UNII：

08V52GZ3H9

NSC Number：

608000

DSSTox ID：

DTXSID5046853

NCI Thesaurus Code：

C71025

HScode：

2924299090

Characteristics

PSA：

66.4

XLogP3：

5.4

Appearance：

white to off-white

Density：

1.2±0.1 g/cm3

Melting Point：

231-232 °C @ Solvent: Diethyl ether, Hexane

Boiling Point：

449.6°C at 760 mmHg

Flash Point：

225.7±28.7 °C

Refractive Index：

1.593

Water Solubility：

soluble to 50 mM in DMSO

Storage Conditions：

Store at RT

Safety Information

Transport codes：

NONH for all modes of transport

wgk germany：

RTECS Number：

DH6940000

Toxicity

Protein Binding：

Over 99%, predominantly to serum albumin.

Drug Information

Drug Indication：

Investigated for use/treatment in leukemia (unspecified).

Pharmacology：

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).

MeSH Entry Terms：

4-((5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)carbamoyl)benzoic acid

Tamibarotene Use and Manufacturing

Uses

A RARα agonist that induces differentiation and apoptosis

Use Classification：

Human drugs -> Rare disease (orphan)

Computed Properties

Molecular Weight:351.4
XLogP3:5.4
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:3
Exact Mass:351.18344366
Monoisotopic Mass:351.18344366
Topological Polar Surface Area:66.4
Heavy Atom Count:26
Complexity:546
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes