AROTINOID ACID

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 Search

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

Molecular Formula	C24H28O2
Molecular Weight	348.4779
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	1
Optical Activity	NONE

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/9070355 | http://www.sciencedirect.com/science/article/pii/S0040403912012762 | https://www.ncbi.nlm.nih.gov/pubmed/15856029

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 Target	Pharmacology	Potency
Retinoic acid receptor gamma 18 Target ID: CHEMBL2003 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9070355 \| https://www.ncbi.nlm.nih.gov/pubmed/10495774	Agonist 2752	9.3 nM [IC50]
Retinoic acid receptor alpha 11 Target ID: CHEMBL2055 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9070355 \| https://www.ncbi.nlm.nih.gov/pubmed/10495774	Agonist 2752	5.1 nM [IC50]
Retinoid X receptor beta 3 Target ID: CHEMBL1870 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9070355 \| https://www.ncbi.nlm.nih.gov/pubmed/10495774	Agonist 2752	4.5 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Prostate cancer 186 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15126374	Primary	Basic research	Unknown Approved Use Unknown
Breast cancer 432 Sources: https://www.ncbi.nlm.nih.gov/pubmed/3007157 https://www.ncbi.nlm.nih.gov/pubmed/9877028	Primary	Preclinical	Unknown Approved Use Unknown
Psoriasis 87 Sources: https://www.ncbi.nlm.nih.gov/pubmed/3378655 https://www.ncbi.nlm.nih.gov/pubmed/1376755 https://www.ncbi.nlm.nih.gov/pubmed/3315625	Primary	Preclinical	Unknown Approved Use Unknown
Pancreatic cancer 98 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15856029	Primary	Basic research	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Chemical genomics profiling of environmental chemical modulation of human nuclear receptors.	2011-08	21543282
Nuclear receptor agonists improve insulin responsiveness in cultured cardiomyocytes through enhanced signaling and preserved cytoskeletal architecture.	2008-03	18063688
The farnesoid X receptor FXRalpha/NR1H4 acquired ligand specificity for bile salts late in vertebrate evolution.	2007-09	17567710
Modulation of aromatase activity and mRNA by various selected pesticides in the human choriocarcinoma JEG-3 cell line.	2006-11-10	16996190
Retinoic acid regulates the expression of photoreceptor transcription factor NRL.	2006-09-15	16854989
[Mechanism of receptor for retinoids inducing apoptosis of human melanoma cell line A375].	2006-07	16909596
Akt phosphorylates and suppresses the transactivation of retinoic acid receptor alpha.	2006-05-01	16417524
Receptor-selective retinoids inhibit the growth of normal and malignant breast cells by inducing G1 cell cycle blockade.	2006-03	16273314
Retinoid-mediated stimulation of steroid sulfatase activity in myeloid leukemic cell lines requires RARalpha and RXR and involves the phosphoinositide 3-kinase and ERK-MAP kinase pathways.	2006-02-01	16178010
Retinoic acid receptors and tissue-transglutaminase mediate short-term effect of retinoic acid on migration and invasion of neuroblastoma SH-SY5Y cells.	2006-01-12	16158052
Retinoic acids increase expression of GLUT4 in dedifferentiated and hypertrophied cardiac myocytes.	2006-01	16273324
Mechanism of retinoid receptors in inhibiting proliferation and inducing apoptosis of human melanoma cell line A375.	2005-09-05	16157052
[Receptor-related mechanism of proliferation inhibilion and apoptosis induetion of human tongue squamous cell line Tca8113 by retinoids].	2005-08	16109544
Activation of retinoic acid receptor-dependent transcription by organochlorine pesticides.	2005-01-01	15589975
Regulation of differentiating pig preadipocytes by retinoic acid.	2005-01	15583048
Upregulation of connexin 43 by retinoids but not by non-provitamin A carotenoids requires RARs.	2005	16091010
PPARbeta regulates vitamin A metabolism-related gene expression in hepatic stellate cells undergoing activation.	2003-02	12576510
Retinoic acid stimulates the cell cycle machinery in normal T cells: involvement of retinoic acid receptor-mediated IL-2 secretion.	2002-11-15	12421932
Structural basis for isotype selectivity of the human retinoic acid nuclear receptor.	2000-09-08	10964567
TCDD suppression of tissue transglutaminase stimulation by retinoids in malignant human keratinocytes.	2000-08	10910994
Both retinoic-acid-receptor- and retinoid-X-receptor-dependent signalling pathways mediate the induction of the brown-adipose-tissue-uncoupling-protein-1 gene by retinoids.	2000-01-01	10600643
Therapeutic applications for ligands of retinoid receptors.	2000-01	10637371
Activation of retinoid X receptors induces apoptosis in HL-60 cell lines.	1995-07	7791761
Different agonist- and antagonist-induced conformational changes in retinoic acid receptors analyzed by protease mapping.	1994-01	8264595

Patents

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.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 19:16:21 GMT 2025` Edited by `admin` on `Mon Mar 31 19:16:21 GMT 2025`
Record UNII	673M8C29UR
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

AGN-191183

Preferred Name

English

AROTINOID ACID

Common Name

English

TTNPB

Common Name

English

(E)-4-(2-(5,6,7,8-TETRAHYDRO-5,5,8,8-TETRAMETHYL-2-NAPHTHALENYL)-1-PROPEN-1-YL)BENZOIC ACID

Systematic Name

English

RO-137410

Code

English

AROTINOIC ACID

Common Name

English

RO 13-7410

Code

English

Code System Code Type Description

EPA CompTox

DTXSID6040743