TRETINOIN

First approved in 1982

Details

Stereochemistry	ACHIRAL
Molecular Formula	C20H28O2
Molecular Weight	300.4351
Optical Activity	UNSPECIFIED
Defined Stereocenters	0 / 0
E/Z Centers	4
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(\C=C\C1=C(C)CCCC1(C)C)=C/C=C/C(C)=C/C(O)=O

InChI

InChIKey=SHGAZHPCJJPHSC-YCNIQYBTSA-N

InChI=1S/C20H28O2/c1-15(8-6-9-16(2)14-19(21)22)11-12-18-17(3)10-7-13-20(18,4)5/h6,8-9,11-12,14H,7,10,13H2,1-5H3,(H,21,22)/b9-6+,12-11+,15-8+,16-14+

HIDE SMILES / InChI

Description

Alitretinoin, or 9-cis-retinoic acid, is a form of vitamin A. It is also used in medicine as an antineoplastic (anti-cancer) agent developed by Ligand Pharmaceuticals. Alitretinoin (9-cis-retinoic acid) is a naturally-occurring endogenous retinoid indicated for topical treatment of cutaneous lesions in patients with AIDS-related Kaposi's sarcoma. Alitretinoin inhibits the growth of Kaposi's sarcoma (KS) cells in vitro. Alitretinoin binds to and activates all known intracellular retinoid receptor subtypes (RARa, RARb, RARg, RXRa, RXRb and RXRg). Once activated these receptors function as transcription factors that regulate the expression of genes that control the process of cellular differentiation and proliferation in both normal and neoplastic cells. In the United States, topical alitretinoin (in the form of a gel; trade name Panretin) is indicated for the treatment of skin lesions in AIDS-related Kaposi's sarcoma.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Retinoid X receptor alpha 9	Agonist 2361	Sarcoma, Kaposi	10.0 nM [EC50]
Retinoic acid receptor beta 16	Agonist 2361	Sarcoma, Kaposi	3.0 nM [EC50]
Retinoid X receptor alpha 9	Agonist 2361	Sarcoma, Kaposi	195.0 nM [EC50]
Retinoic acid receptor gamma 15	Agonist 2361	Sarcoma, Kaposi	50.0 nM [EC50]
Retinoid X receptor gamma 6	Agonist 2361	Sarcoma, Kaposi	140.0 nM [EC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Acne 77	Primary		Approved 7883	ACCUTANE
Sarcoma, Kaposi 12	Primary	Retinoid X receptor alpha Retinoid X receptor alpha Retinoic acid receptor beta Retinoid X receptor gamma Retinoic acid receptor gamma	Approved 7883	Panretin gel
Severe chronic hand eczema 4			Approved (off-label) 8

PubMed

Title	Date	PubMed
Effects of xenobiotics and peroxisome proliferator-activated receptor-alpha on the human UDPglucose dehydrogenase gene expression.	2005	16292757
The detection of differentiation-inducing chemicals by using green fluorescent protein expression in genetically engineered teratocarcinoma cells.	2005 Apr	16180984
[Receptor-related mechanism of proliferation inhibilion and apoptosis induetion of human tongue squamous cell line Tca8113 by retinoids].	2005 Aug	16109544
Retinoic acid induces VEGF gene expression in human retinal pigment epithelial cells (ARPE-19).	2005 Dec	16386082
Coactivation of liver receptor homologue-1 by peroxisome proliferator-activated receptor gamma coactivator-1alpha on aromatase promoter II and its inhibition by activated retinoid X receptor suggest a novel target for breast-specific antiestrogen therapy.	2005 Dec 15	16357189
Retinoid x receptor agonists increase bcl2a1 expression and decrease apoptosis of naive T lymphocytes.	2005 Dec 15	16339527
Nuclear import of the retinoid X receptor, the vitamin D receptor, and their mutual heterodimer.	2005 Dec 2	16204233
Open-label pilot study of alitretinoin gel 0.1% in the treatment of photoaging.	2005 Jul	16144296
A new retinoid-like compound that activates peroxisome proliferator-activated receptors and lowers blood glucose in diabetic mice.	2005 Jul	15997096
Specificity of receptor-ligand interactions and their effect on dimerisation as observed by electrospray mass spectrometry: bile acids form stable adducts to the RXRalpha.	2005 Nov	16258897
Effect of retinoic acid on murine preosteoblastic MC3T3-E1 cells.	2005 Oct	16392701
Regulation of a highly specific retinoic acid-4-hydroxylase (CYP26A1) enzyme and all-trans-retinoic acid metabolism in human intestinal, liver, endothelial, and acute promyelocytic leukemia cells.	2005 Oct	16194896
Hepatocyte growth factor receptor signaling mediates the anti-fibrotic action of 9-cis-retinoic acid in glomerular mesangial cells.	2005 Oct	16192631
Arsenic trioxide inhibits nuclear receptor function via SEK1/JNK-mediated RXRalpha phosphorylation.	2005 Oct	16184197
Liver X receptor and retinoic X receptor agonists modulate the expression of genes involved in lipid metabolism in human endothelial cells.	2005 Oct	16142410
The human ABCG1 gene: identification of LXR response elements that modulate expression in macrophages and liver.	2005 Oct	16024918
Physiological and receptor-selective retinoids modulate interferon gamma signaling by increasing the expression, nuclear localization, and functional activity of interferon regulatory factor-1.	2005 Oct 28	16085646
VPAC1 expression is regulated by FXR agonists in the human gallbladder epithelium.	2005 Sep	16037943
Regulation of adiponectin receptor 1 in human hepatocytes by agonists of nuclear receptors.	2005 Sep 2	16023994
The human tumor antigen PRAME is a dominant repressor of retinoic acid receptor signaling.	2005 Sep 23	16179254
Regression of NMU-induced mammary tumors with the combination of melatonin and 9-cis-retinoic acid.	2005 Sep 8	16051031
Organ-specific expression profiles of rat mammary gland, liver, and lung tissues treated with targretin, 9-cis retinoic acid, and 4-hydroxyphenylretinamide.	2006 Apr	16648578
Effects of PPAR and RXR ligands in semaphorin 6B gene expression of human MCF-7 breast cancer cells.	2006 Apr	16525649
Organotin compounds enhance 17beta-hydroxysteroid dehydrogenase type I activity in human choriocarcinoma JAr cells: potential promotion of 17beta-estradiol biosynthesis in human placenta.	2006 Apr 28	16513093
Differential regulation of CC chemokine receptors by 9-cis retinoic acid in the human mast cell line, HMC-1.	2006 Aug 22	16712875
TGIF inhibits retinoid signaling.	2006 Feb	16428452
9-Cis-retinoic acid suppresses inflammatory responses of microglia and astrocytes.	2006 Feb	16303184
Nonclassical action of retinoic acid on the activation of the cAMP response element-binding protein in normal human bronchial epithelial cells.	2006 Feb	16280361
Prostate cancer cell type-specific involvement of the VDR and RXR in regulation of the human PTHrP gene via a negative VDRE.	2006 Feb	16243370
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	16178010
Analysis of ligand binding and protein dynamics of human retinoid X receptor alpha ligand-binding domain by nuclear magnetic resonance.	2006 Feb 14	16460010
Investigation of the mechanisms by which EB1089 abrogates apoptosis induced by 9-cis retinoic acid in pancreatic cancer cells.	2006 Jan	16340750
Vitamin A inhibits pancreatic stellate cell activation: implications for treatment of pancreatic fibrosis.	2006 Jan	16043492
Retinoic acid receptors and tissue-transglutaminase mediate short-term effect of retinoic acid on migration and invasion of neuroblastoma SH-SY5Y cells.	2006 Jan 12	16158052
Effects of 9-cis retinoic acid on human homeobox gene NKX3.1 expression in prostate cancer cell line LNCaP.	2006 Jul	16763719
Retinoic acids increase P2X2 receptor expression through the 5'-flanking region of P2rx2 gene in rat phaeochromocytoma PC-12 cells.	2006 Jul	16638968
Retinoids activate the RXR/SXR-mediated pathway and induce the endogenous CYP3A4 activity in Huh7 human hepatoma cells.	2006 Jul	16632523
Peroxisome proliferator-activated receptor-gamma and retinoic acid X receptor alpha represses the TGFbeta1 gene via PTEN-mediated p70 ribosomal S6 kinase-1 inhibition: role for Zf9 dephosphorylation.	2006 Jul	16611854
A novel cytochrome P450, zebrafish Cyp26D1, is involved in metabolism of all-trans retinoic acid.	2006 Jul	16455818
Thiazolidinediones and rexinoids induce peroxisome proliferator-activated receptor-coactivator (PGC)-1alpha gene transcription: an autoregulatory loop controls PGC-1alpha expression in adipocytes via peroxisome proliferator-activated receptor-gamma coactivation.	2006 Jun	16513826
Efficacy of new retinoids in the prevention of mammary cancers and correlations with short-term biomarkers.	2006 Jun	16344269
CYP4A11 is repressed by retinoic acid in human liver cells.	2006 Jun 12	16712844
Co-resistance to retinoic acid and TRAIL by insertion mutagenesis into RAM.	2006 Jun 22	16449964
Effects of rexinoids on thyrotrope function and the hypothalamic-pituitary-thyroid axis.	2006 Mar	16306084
Receptor-selective retinoids inhibit the growth of normal and malignant breast cells by inducing G1 cell cycle blockade.	2006 Mar	16273314
The phosphoinositide 3-kinase/Akt pathway is essential for the retinoic acid-induced differentiation of F9 cells.	2006 Mar 30	16288212
Retinoic acid exerts dual regulatory actions on the expression and nuclear localization of interferon regulatory factor-1.	2006 May	16636311
9-cis-Retinoic acid inhibition of lung carcinogenesis in the A/J mouse model is accompanied by increased expression of RAR-beta but no change in cyclooxygenase-2.	2006 Nov 28	16413115
Molecular cloning of the rat beta-carotene 15,15'-monooxygenase gene and its regulation by retinoic acid.	2006 Sep	16699835
Unsaturated fatty acids suppress the expression of the ATP-binding cassette transporter G1 (ABCG1) and ABCA1 genes via an LXR/RXR responsive element.	2007 Mar	16730733

Patents

Sample Use Guides

In Vivo Use Guide

Panretin (Alitretinoin) gel should initially be applied two (2) times a day to cutaneous KS lesions. The application frequency can be gradually increased to three (3) or four (4) times a day according to individual lesion tolerance.

Route of Administration: Topical

In Vitro Use Guide

The addition of 5 nM Alitretinoin to the maturation medium was beneficial for parthenogenetic pig embryo production.

Name

Type

Language

TRETINOIN

Official Name

English

TRETINOIN [ORANGE BOOK]

Common Name

English

ORISTAR RNA

Brand Name

English

TRETINOIN [JAN]

Common Name

English

RETINOIC ACID [MI]

Common Name

English

RETIN-A

Brand Name

English

TRETINOIN COMPONENT OF VELTIN

Brand Name

English

TRETINOIN COMPONENT OF SOLAGE

Common Name

English

TRETINOIN [USP-RS]

Common Name

English

TRI-LUMA COMPONENT TRETINOIN

Common Name

English

SOLAGE COMPONENT TRETINOIN

Common Name

English

VESANOID

Brand Name

English

TRETINOIN [VANDF]

Common Name

English

RETINOIC ACID

Official Name

English

TRETINOIN [EP]

Common Name

English

RETIN A

Brand Name

English

TRETINOIN [USAN]

Common Name

English

TRETINOIN [MART.]

Common Name

English

TRETINOIN [HSDB]

Common Name

English

NSC-122758

Code

English

TRETINOIN COMPONENT OF TRI-LUMA

Common Name

English

TRETINOIN [USP]

Common Name

English

KERLOCAL

Brand Name

English

TRETINOIN [WHO-DD]

Common Name

English

ZIANA COMPONENT TRETINOIN

Common Name

English

TRETINOIN COMPONENT OF ZIANA

Common Name

English

TRETINOIN [INN]

Common Name

English

RENOVA

Brand Name

English

ATRA

Common Name

English

ALTRENO

Brand Name

English

EUDYNA

Brand Name

English

ABEREL

Brand Name

English

ALL-TRANS-RETINOIC ACID

Common Name

English

ALL-TRANS RETINOIC ACID

Common Name

English

AVITA

Brand Name

English

VELTIN COMPONENT TRETINOIN

Brand Name

English

RETINOIC ACID [INCI]

Common Name

English

TRETINOIN MICROSPHERE

Common Name

English

Classification Tree Code System Code

NDF-RT

N0000007700