U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

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

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

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.

Approval Year

PubMed

PubMed

TitleDatePubMed
Different agonist- and antagonist-induced conformational changes in retinoic acid receptors analyzed by protease mapping.
1994 Jan
Upregulation of connexin 43 by retinoids but not by non-provitamin A carotenoids requires RARs.
2005
Mechanism of retinoid receptors in inhibiting proliferation and inducing apoptosis of human melanoma cell line A375.
2005 Sep 5
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 Feb 1
Retinoic acid regulates the expression of photoreceptor transcription factor NRL.
2006 Sep 15
Nuclear receptor agonists improve insulin responsiveness in cultured cardiomyocytes through enhanced signaling and preserved cytoskeletal architecture.
2008 Mar
Patents

Sample Use Guides

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
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 Fri Dec 15 18:36:07 UTC 2023
Edited
by admin
on Fri Dec 15 18:36:07 UTC 2023
Record UNII
673M8C29UR
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
AROTINOID ACID
Common Name English
AGN-191183
Code 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
Created by admin on Fri Dec 15 18:36:07 UTC 2023 , Edited by admin on Fri Dec 15 18:36:07 UTC 2023
PRIMARY
CAS
71441-28-6
Created by admin on Fri Dec 15 18:36:07 UTC 2023 , Edited by admin on Fri Dec 15 18:36:07 UTC 2023
PRIMARY
CHEBI
75261
Created by admin on Fri Dec 15 18:36:07 UTC 2023 , Edited by admin on Fri Dec 15 18:36:07 UTC 2023
PRIMARY
DRUG BANK
DB02877
Created by admin on Fri Dec 15 18:36:07 UTC 2023 , Edited by admin on Fri Dec 15 18:36:07 UTC 2023
PRIMARY
FDA UNII
673M8C29UR
Created by admin on Fri Dec 15 18:36:07 UTC 2023 , Edited by admin on Fri Dec 15 18:36:07 UTC 2023
PRIMARY
PUBCHEM
5289501
Created by admin on Fri Dec 15 18:36:07 UTC 2023 , Edited by admin on Fri Dec 15 18:36:07 UTC 2023
PRIMARY
Related Record Type Details
ACTIVE MOIETY