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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 of TRETINOIN

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

Molecular Formula C20H28O2
Molecular Weight 300.4351
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry
Defined Stereocenters 0 / 0
E/Z Centers 4
Optical Activity NONE

Description

All-trans retinoic acid (ATRA) also known as tretinoin is an active metabolite of vitamin A that has been demonstrated to inhibit the growth of cancer cells, some types of epithelial cells, and vascular smooth muscles. It is medication used for the treatment of acne. Tretinoin capsules are indicated for the induction of remission in patients with acute promyelocytic leukemia (APL), French-American-British (FAB) classification M3 (including the M3 variant), characterized by the presence of the t(15;17) translocation and/or the presence of the PML/RARα gene who are refractory to, or who have relapsed from, anthracycline chemotherapy, or for whom anthracycline based chemotherapy is contraindicated. Tretinoin is for the induction of remission only. For acne it is applied to the skin as a cream or ointment. For leukemia it is taken by mouth for up to three months. The exact mechanism of action of tretinoin in APL and acne treatment is unknown, but is known, that tretinoin activates three members of the retinoid acid (RAR) nuclear receptors (RARα, RARβ, and RARγ) which act to modify gene expression, subsequent protein synthesis, and epithelial cell growth and differentiation. It has not been established whether the clinical effects of tretinoin are mediated through activation of retinoic acid receptors, other mechanisms, or both.

CNS Activity

Originator

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
RETIN-A
Palliative
TRETINOIN
PubMed

PubMed

TitleDatePubMed
[Fatal side-effects of all-trans retinoic acid in the treatment of acute promyelocytic leukemia].
1999
[An analysis of the therapeutic effects and reactions in treating acute promyelocytic leukemia with intravenous arsenic trioxide or all-trans retinoic acid].
1999 Feb
[Effects of all-trans retinoic acid, arsenic trioxide and daunorubicin on tissue factor expression in NB4 cells].
1999 Sep
Carotenoids and retinoids as suppressors on adipocyte differentiation via nuclear receptors.
2000
Biological effects and metabolism of 9-cis-retinoic acid and its metabolite 9,13-di-cis-retinoic acid in HaCaT keratinocytes in vitro: comparison with all-trans-retinoic acid.
2000 Dec
[Severe side effects of the treatment of acute promyelocytic leukemia with all-trans retinoic acid].
2000 Jun 28
Hemostatic abnormalities associated with acute promyelocytic leukemia and corrective effects of all-trans-retinoic acid or arsenic trioxide treatment.
2000 Mar
[Mechanism of tissue factor expression on NB4 cells down-regulated by all-trans retinoic acid and arsenic trioxide].
2000 May
[Effects of all-trans retinoic acid and arsenic trioxide on tissue factor expression of acute promyelocytic leukemia cells].
2000 May
Pseudotumor cerebri caused by all-trans-retinoic acid: a case report.
2000 Nov
Inhibitors of human immunodeficiency virus type 1 reverse transcriptase target distinct phases of early reverse transcription.
2001 Apr
Regulation of aquaporin-4 expression in astrocytes.
2001 Apr 18
Carnosic acid and promotion of monocytic differentiation of HL60-G cells initiated by other agents.
2001 Aug 15
Hypercalcemia due to all-trans retinoic acid therapy for acute promyelocytic leukemia: a case report of effective treatment with bisphosphonate.
2001 Dec
Retinoic acid-mediated growth arrest requires ubiquitylation and degradation of the F-box protein Skp2.
2001 Dec 7
[A study of tissue factor expression and hemostatic molecular markers in patients with acute promyelocytic leukemia].
2001 Jan
Effect of all-trans retinoic acid and arsenic trioxide on tissue factor expression in acute promyelocytic leukemia cells.
2001 Jan
Retinoid receptors in human breast carcinoma: possible modulators of in situ estrogen metabolism.
2001 Jan
Regulation of IL-5 receptor on eosinophil progenitors in allergic inflammation: role of retinoic acid.
2001 Jan-Mar
Inhibitors of arachidonic acid metabolism potentiate tumour necrosis factor-alpha-induced apoptosis in HL-60 cells.
2001 Jul 13
Retinoic acid-induced apoptosis in leukemia cells is mediated by paracrine action of tumor-selective death ligand TRAIL.
2001 Jun
Short heterodimer partner (SHP) orphan nuclear receptor inhibits the transcriptional activity of aryl hydrocarbon receptor (AHR)/AHR nuclear translocator (ARNT).
2001 Jun 1
Expression of retinoic acid receptor gamma correlates with retinoic acid sensitivity and metabolism in head and neck squamous cell carcinoma cell lines.
2001 Jun 1
Proteolysis of integrin alpha5 and beta1 subunits involved in retinoic acid-induced apoptosis in human hepatoma Hep3B cells.
2001 Jun 26
Characterization of a novel airway epithelial cell-specific short chain alcohol dehydrogenase/reductase gene whose expression is up-regulated by retinoids and is involved in the metabolism of retinol.
2001 Jun 29
Expression and regulation of chicken fibroblast growth factor homologous factor (FHF)-4 during craniofacial morphogenesis.
2001 Mar
1,25-dihydroxyvitamin D3 and retonic acid analogues induce differentiation in breast cancer cells with function- and cell-specific additive effects.
2001 May
Retinoic acid administration is associated with changes in the extracellular matrix and cardiac mesenchyme within the endocardial cushion.
2001 May 1
Benign thymic hyperplasia after chemotherapy for acute myeloid leukemia.
2001 Oct
Retinoic acid prevents experimental Cushing syndrome.
2001 Oct
Retinoic acid enhances the cytotoxic effects of gemcitabine and cisplatin in pancreatic adenocarcinoma cells.
2001 Oct
All-trans-retinoic acid increased the expression of integrin alpha5beta1 and induced "anoikis" in SMMC-7721 hepatocarcinoma cell.
2001 Sep
All-trans retinoic acid inhibits vascular smooth muscle cell proliferation targeting multiple genes for cyclins and cyclin-dependent kinases.
2001 Sep
Granulomatous tubulointerstitial nephritis induced by all-trans retinoic acid.
2001 Sep
Arsenic trioxide, retinoic acid and Ara-c regulated the expression of annexin II on the surface of APL cells, a novel co-receptor for plasminogen/tissue plasminogen activator.
2002 Apr 1
Targeted removal of PML-RARalpha protein is required prior to inhibition of histone deacetylase for overcoming all-trans retinoic acid differentiation resistance in acute promyelocytic leukemia.
2002 Aug 1
[Study of the effects of quercetin on PML gene and protein expression and localization in leukemia cells].
2002 Feb
Sequential induction of embryonic and adult forms of glutamic acid decarboxylase during in vitro-induced neurogenesis in cloned neuroectodermal cell-line, NE-7C2.
2002 Feb
Radiologic features of all-trans-retinoic acid syndrome.
2002 Feb
All-trans retinoic acid induces differentiation and apoptosis of murine melanocyte precursors with induction of the microphthalmia-associated transcription factor.
2002 Jan
The efficacy of endocrine disruptor screening tests in detecting anti-estrogenic effects downstream of receptor-ligand interactions.
2002 Jan 25
Gene-specific TCDD suppression of RARalpha- and RXR-mediated induction of tissue transglutaminase.
2002 Jul
Down-regulation of the phosphatidylinositol 3-kinase/Akt pathway is involved in retinoic acid-induced phosphorylation, degradation, and transcriptional activity of retinoic acid receptor gamma 2.
2002 Jul 12
Transient dilated cardiomyopathy in a newborn exposed to idarubicin and all-trans-retinoic acid (ATRA) early in the second trimester of pregnancy.
2002 Jul-Aug
Excentric cleavage products of beta-carotene inhibit estrogen receptor positive and negative breast tumor cell growth in vitro and inhibit activator protein-1-mediated transcriptional activation.
2002 Jun
All trans retinoic acid enhances CDDP-induced apoptosis: modulation of the CDDP effect on cell cycle progression.
2002 Jun
Pathogenesis of murine experimental allergic rhinitis: a study of local and systemic consequences of IL-5 deficiency.
2002 Mar 15
[Genetic dissection of retinoic acid function in epidermis physiology].
2002 May
Analysis of cartilage-derived retinoic-acid-sensitive protein (CD-RAP) in synovial fluid from patients with osteoarthritis and rheumatoid arthritis.
2002 Sep
All-trans-retinoic acid induces CD52 expression in acute promyelocytic leukemia.
2003 Mar 1
Patents

Sample Use Guides

In Vivo Use Guide
acute promyelocytic leukemia (APL): The recommended dose is 45 mg/m2/day administered as two evenly divided doses until complete remission is documented. Therapy should be discontinued 30 days after achievement of complete remission or after 90 days of treatment, whichever occurs first. acne vulgaris: RETIN-A Gel, Cream or Liquid should be applied once a day, before retiring, to the skin where acne lesions appear, using enough to cover the entire affected area lightly. Liquid: the liquid may be applied using a fingertip, gauze pad, or cotton swab. If gauze or cotton is employed, care should be taken not to oversaturate it, to the extent that the liquid would run into areas where treatment is not intended. Gel: Excessive application results in “pilling” of the gel, which minimizes the likelihood of over application by the patient.
Route of Administration: topical; oral
In Vitro Use Guide
Human bronchial SMCs were used and pretreated with or without tretinoin, also known as all-trans-retinoic acid (ATRA), (2 μM) for 20 min before the addition of PDGF (1 μg/ml), or ATRA alone. The neutral comet assay, which determines the incidence of double-stranded DNA breaks, was used to demonstrate that ATRA treatment induced apoptosis of bovine and human pulmonary artery SMC. In contrast, apoptotic cell death was not produced in response to ATRA in human bronchial airway SMC, as monitored by comet assay. Similarly, TUNEL assay and the measurement of mitochondrial membrane potential failed to demonstrate significant apoptosis by ATRA in airway SMCs. Positive controls, daunorubicin (DNR) and hydrogen peroxide, effectively elicited apoptosis in airway SMC. Because ATRA inhibited both morphologic and actin cytoskeletal changes induced by PDGF, it was characterized the effects of ATRA on PDGF-induced airway SMC migration using a modified Boyden chamber assay, which allows for determination of motility in random directions. PDGF caused a 4-fold increase in migration of airway SMCs after 24 h, and ATRA blocked these events. ATRA by itself had no effect. While the therapeutic level of ATRA in human plasma could reach 1–2 μM, the effects on airway SMC migration were observed with ATRA concentrations as low as 0.2 μM. DMSO, which is used as vehicle for ATRA and other retinoids, has no effect on PDGF-induced airway SMC migration. This does not appear to be due to the effects of ATRA on cell proliferation, as MTT assay showed that ATRA is not effective in inhibiting PDGF-induced cell proliferation; additionally, migration assay with 4 h of PDGF treatment also exhibits the ability of ATRA to inhibit migratory responses, as monitored using a modified Boyden chamber assay. Thus, although ATRA is ineffective in inhibiting proliferation and inducing apoptosis of airway SMCs, ATRA is an efficient inhibitor of airway SMC migration. Furthermore, using actinomycin D, a general inhibitor of gene transcription, showed that ATRA inhibition of SMC migration does not mediate gene transcriptional events.
Substance Class Chemical
Created
by admin
on Mon Oct 21 19:53:20 UTC 2019
Edited
by admin
on Mon Oct 21 19:53:20 UTC 2019
Record UNII
5688UTC01R
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
TRETINOIN
EP   HSDB   INN   JAN   MART.   ORANGE BOOK   USAN   USP   USP-RS   VANDF   WHO-DD  
USAN   INN  
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
INCI   MI  
INCI  
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
Created by admin on Mon Oct 21 19:53:20 UTC 2019 , Edited by admin on Mon Oct 21 19:53:20 UTC 2019
NDF-RT N0000175607
Created by admin on Mon Oct 21 19:53:20 UTC 2019 , Edited by admin on Mon Oct 21 19:53:20 UTC 2019
NCI_THESAURUS C68299
Created by admin on Mon Oct 21 19:53:20 UTC 2019 , Edited by admin on Mon Oct 21 19:53:20 UTC 2019
WHO-VATC QL01XX14
Created by admin on Mon Oct 21 19:53:20 UTC 2019 , Edited by admin on Mon Oct 21 19:53:20 UTC 2019
FDA ORPHAN DRUG 71692
Created by admin on Mon Oct 21 19:53:20 UTC 2019 , Edited by admin on Mon Oct 21 19:53:20 UTC 2019
NCI_THESAURUS C804
Created by admin on Mon Oct 21 19:53:20 UTC 2019 , Edited by admin on Mon Oct 21 19:53:20 UTC 2019
FDA ORPHAN DRUG 5785
Created by admin on Mon Oct 21 19:53:20 UTC 2019 , Edited by admin on Mon Oct 21 19:53:20 UTC 2019
FDA ORPHAN DRUG 165802
Created by admin on Mon Oct 21 19:53:20 UTC 2019 , Edited by admin on Mon Oct 21 19:53:20 UTC 2019
WHO-VATC QD10AD51
Created by admin on Mon Oct 21 19:53:20 UTC 2019 , Edited by admin on Mon Oct 21 19:53:20 UTC 2019
FDA ORPHAN DRUG 50990
Created by admin on Mon Oct 21 19:53:20 UTC 2019 , Edited by admin on Mon Oct 21 19:53:20 UTC 2019
WHO-ATC D10AD51
Created by admin on Mon Oct 21 19:53:20 UTC 2019 , Edited by admin on Mon Oct 21 19:53:20 UTC 2019
NDF-RT N0000007700
Created by admin on Mon Oct 21 19:53:20 UTC 2019 , Edited by admin on Mon Oct 21 19:53:20 UTC 2019
NDF-RT N0000007700
Created by admin on Mon Oct 21 19:53:20 UTC 2019 , Edited by admin on Mon Oct 21 19:53:20 UTC 2019
WHO-ATC D10AD01
Created by admin on Mon Oct 21 19:53:20 UTC 2019 , Edited by admin on Mon Oct 21 19:53:20 UTC 2019
WHO-VATC QD10AD01
Created by admin on Mon Oct 21 19:53:20 UTC 2019 , Edited by admin on Mon Oct 21 19:53:20 UTC 2019
WHO-ATC L01XX14
Created by admin on Mon Oct 21 19:53:20 UTC 2019 , Edited by admin on Mon Oct 21 19:53:20 UTC 2019
NDF-RT N0000007700
Created by admin on Mon Oct 21 19:53:20 UTC 2019 , Edited by admin on Mon Oct 21 19:53:20 UTC 2019
NDF-RT N0000007700
Created by admin on Mon Oct 21 19:53:20 UTC 2019 , Edited by admin on Mon Oct 21 19:53:20 UTC 2019
LIVERTOX 993
Created by admin on Mon Oct 21 19:53:20 UTC 2019 , Edited by admin on Mon Oct 21 19:53:20 UTC 2019
Code System Code Type Description
ChEMBL
CHEMBL38
Created by admin on Mon Oct 21 19:53:20 UTC 2019 , Edited by admin on Mon Oct 21 19:53:20 UTC 2019
PRIMARY
MERCK INDEX
M9558
Created by admin on Mon Oct 21 19:53:20 UTC 2019 , Edited by admin on Mon Oct 21 19:53:20 UTC 2019
PRIMARY Merck Index
INN
2875
Created by admin on Mon Oct 21 19:53:20 UTC 2019 , Edited by admin on Mon Oct 21 19:53:20 UTC 2019
PRIMARY
PUBCHEM
444795
Created by admin on Mon Oct 21 19:53:20 UTC 2019 , Edited by admin on Mon Oct 21 19:53:20 UTC 2019
PRIMARY
RXCUI
221175
Created by admin on Mon Oct 21 19:53:20 UTC 2019 , Edited by admin on Mon Oct 21 19:53:20 UTC 2019
ALTERNATIVE
NCI_THESAURUS
C900
Created by admin on Mon Oct 21 19:53:20 UTC 2019 , Edited by admin on Mon Oct 21 19:53:20 UTC 2019
PRIMARY
WIKIPEDIA
TRETINOIN
Created by admin on Mon Oct 21 19:53:20 UTC 2019 , Edited by admin on Mon Oct 21 19:53:20 UTC 2019
PRIMARY
RXCUI
10753
Created by admin on Mon Oct 21 19:53:20 UTC 2019 , Edited by admin on Mon Oct 21 19:53:20 UTC 2019
PRIMARY
LactMed
302-79-4
Created by admin on Mon Oct 21 19:53:20 UTC 2019 , Edited by admin on Mon Oct 21 19:53:20 UTC 2019
PRIMARY
DRUG BANK
DB00755
Created by admin on Mon Oct 21 19:53:20 UTC 2019 , Edited by admin on Mon Oct 21 19:53:20 UTC 2019
PRIMARY
CAS
302-79-4
Created by admin on Mon Oct 21 19:53:20 UTC 2019 , Edited by admin on Mon Oct 21 19:53:20 UTC 2019
PRIMARY
IUPHAR
2644
Created by admin on Mon Oct 21 19:53:20 UTC 2019 , Edited by admin on Mon Oct 21 19:53:20 UTC 2019
PRIMARY
HSDB
302-79-4
Created by admin on Mon Oct 21 19:53:20 UTC 2019 , Edited by admin on Mon Oct 21 19:53:20 UTC 2019
PRIMARY
EVMPD
SUB11246MIG
Created by admin on Mon Oct 21 19:53:20 UTC 2019 , Edited by admin on Mon Oct 21 19:53:20 UTC 2019
PRIMARY
EPA CompTox
302-79-4
Created by admin on Mon Oct 21 19:53:20 UTC 2019 , Edited by admin on Mon Oct 21 19:53:20 UTC 2019
PRIMARY
ECHA (EC/EINECS)
206-129-0
Created by admin on Mon Oct 21 19:53:20 UTC 2019 , Edited by admin on Mon Oct 21 19:53:20 UTC 2019
PRIMARY
MESH
D014212
Created by admin on Mon Oct 21 19:53:20 UTC 2019 , Edited by admin on Mon Oct 21 19:53:20 UTC 2019
PRIMARY
Related Record Type Details
SALT/SOLVATE -> PARENT
Related Record Type Details
PARENT -> METABOLITE
Mediator Substance AOX1
METABOLITE -> PARENT
MAJOR
PLASMA
METABOLITE -> PARENT
MAJOR
PLASMA
Related Record Type Details
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
Related Record Type Details
ACTIVE MOIETY