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Details

Stereochemistry ACHIRAL
Molecular Formula C24H28O2
Molecular Weight 348.4779
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of AROTINOID ACID

SMILES

C\C(=C/C1=CC=C(C=C1)C(O)=O)C2=CC=C3C(=C2)C(C)(C)CCC3(C)C

InChI

InChIKey=FOIVPCKZDPCJJY-JQIJEIRASA-N
InChI=1S/C24H28O2/c1-16(14-17-6-8-18(9-7-17)22(25)26)19-10-11-20-21(15-19)24(4,5)13-12-23(20,2)3/h6-11,14-15H,12-13H2,1-5H3,(H,25,26)/b16-14+

HIDE SMILES / InChI

Description

Arotinoid acid (Ro 13-7410, TTNPB) is the third generation of synthetic retinoid, which was developed for the treatment of psoriasis and other hyperkeratotic skin disorders. The therapeutically active dose is less than 0.5 ug/kg body weight/day. Arotinoid Acid is an agonist of RAR with IC50 values of 3.8nM, 4nM and 4.5nM for RARα, RARβ and RARγ, respectively. Naturally occurring vitamin A-like compounds such as all-trans-retinoic acid (atRA) are responsible for regulating growth and differentiation in the cell, and many of them have shown promising anticancer effects. Bioassays in vivo and in culture showed that TTNPB is more potent than atRA, mainly because of its higher molecular stability. The effects of TTNPB, which include control of epidermal keratinocytes and murine teratocarcinoma cells and antiproliferative effects on Kaposi´s sarcoma, breast cancer, cervical carcinoma, and leukemia cells have been known for some time. Furthermore, TTNPB proved to be 100 times more effective than atRA in inhibiting the growth of breast cancer cells. However, TTNPB is more teratogenic than atRA, which limits its use as a chemotherapeutic agent in humans. Arotinoid acid (AGN193198) has being shown to be useful for the treatment of pancreatic cancer among other types of cancer.

Originator

Approval Year

Targets

Primary TargetPharmacologyConditionPotency
9.3 nM [IC50]
5.1 nM [IC50]
4.5 nM [IC50]

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown
Primary
Unknown
Primary
Unknown
Primary
Unknown

PubMed

Sample Use Guides

In Vivo Use Guide
Hamsters: arotinoid acid (TTNPB) was administered as a single oral bolus (100 ug/kg; 0.29 uM/kg; 35 uCi/animal) to pregnant hamsters (day 8). The maximum concentrations of circulating radioactive compound or metabolites after 100 ug/kg [3H]2-TTNPB occurred in liver greater than fetus greater than adrenal greater than lung approximately equal to kidney greater than plasma; after 1000 ug/kg, maternal liver accumulated the highest concentration followed by plasma greater than fetus = placenta = uterus.
Route of Administration: Oral
In Vitro Use Guide
Arotinoid acid (TTNPB) increases transcriptional activation of mouse RARs in JEG-3 cells after 72 h using conditioned media with EC50 of 2.0 nM, 1.1 nM and 0.8 nM for mRARα, β, and γ, respectively.