Details
Stereochemistry | ACHIRAL |
Molecular Formula | C20H28O2 |
Molecular Weight | 300.4351 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 4 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CC(\C=C\C1=C(C)CCCC1(C)C)=C\C=C\C(C)=C\C(O)=O
InChI
InChIKey=SHGAZHPCJJPHSC-ZVCIMWCZSA-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+
DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/16456186 | https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0f81f505-a962-414e-8612-c3ef3b159e9a | https://www.accessdata.fda.gov/drugsatfda_docs/label/2002/16921s21s22s25lbl.pdfhttp://www.drugbank.ca/drugs/DB00523Curator's Comment: Description was created based on several sources, including
http://www.accessdata.fda.gov/drugsatfda_docs/label/1999/20886lbl.pdf
Sources: https://www.ncbi.nlm.nih.gov/pubmed/16456186 | https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0f81f505-a962-414e-8612-c3ef3b159e9a | https://www.accessdata.fda.gov/drugsatfda_docs/label/2002/16921s21s22s25lbl.pdfhttp://www.drugbank.ca/drugs/DB00523
Curator's Comment: Description was created based on several sources, including
http://www.accessdata.fda.gov/drugsatfda_docs/label/1999/20886lbl.pdf
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.
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL2061 |
10.0 nM [EC50] | ||
Target ID: CHEMBL2003 |
50.0 nM [EC50] | ||
Target ID: CHEMBL2061 |
195.0 nM [EC50] | ||
Target ID: CHEMBL2008 |
3.0 nM [EC50] | ||
Target ID: CHEMBL2004 |
140.0 nM [EC50] | ||
Target ID: CHEMBL2363069 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16456186 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | ACCUTANE Approved UseAccutane is indicated for the treatment of severe recalcitrant nodular acne. Nodules are inflammatory lesions with a diameter of 5 mm or greater. The nodules may become suppurative or hemorrhagic. “Severe,” by definition, means “many” as opposed to “few or several” nodules. Because of significant adverse effects associated with its use, Accutane should be reserved for patients with severe nodular acne who are unresponsive to conventional therapy, including systemic antibiotics. In addition, Accutane is indicated only for those female patients who are not pregnant, because Accutane can cause severe birth defects. Launch Date1982 |
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Primary | Panretin gel Approved UsePanretin gel is indicated for topical treatment of cutaneous lesions in patients with AIDS-related Kaposi’s sarcoma. Launch Date1999 |
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Primary | RETIN-A Approved UseRETIN-A is indicated for topical application in the treatment of acne vulgaris. The safety and efficacy of the long-term use of this product in the treatment of other disorders have not been established. Launch Date1971 |
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Palliative | TRETINOIN Approved Useretinoin 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. The optimal consolidation or maintenance regimens have not been defined, but all patients should receive an accepted form of remission consolidation and/or maintenance therapy for APL after completion of induction therapy with tretinoin. Launch Date2007 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
314 ng/mL |
40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered: |
ISOTRETINOIN plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
4055 ng × h/mL |
40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered: |
ISOTRETINOIN plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
24 h |
40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered: |
ISOTRETINOIN plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
Funbound
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
0.1% |
40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered: |
ISOTRETINOIN plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
Doses
Dose | Population | Adverse events |
---|---|---|
12.5 mg/kg single, oral Overdose Dose: 12.5 mg/kg Route: oral Route: single Dose: 12.5 mg/kg Sources: Page: p.348 |
unhealthy, 29 n = 1 Health Status: unhealthy Condition: Acne Age Group: 29 Sex: M Population Size: 1 Sources: Page: p.348 |
Disc. AE: Cheilitis, Skin xerosis... AEs leading to discontinuation/dose reduction: Cheilitis Sources: Page: p.348Skin xerosis Desquamation Headache Skin xerosis |
1000 mg single, oral Overdose Dose: 1000 mg Route: oral Route: single Dose: 1000 mg Sources: Page: p.74 |
unhealthy, 31 n = 1 Health Status: unhealthy Condition: AIDS Age Group: 31 Sex: M Population Size: 1 Sources: Page: p.74 |
Disc. AE: Diarrhea... AEs leading to discontinuation/dose reduction: Diarrhea Sources: Page: p.74 |
100 mg/m2 2 times / day multiple, oral Highest studied dose Dose: 100 mg/m2, 2 times / day Route: oral Route: multiple Dose: 100 mg/m2, 2 times / day Sources: Page: p.897 |
unhealthy, 4 n = 9 Health Status: unhealthy Condition: Neuroblastoma Age Group: 4 Sex: M+F Population Size: 9 Sources: Page: p.897 |
DLT: Hypercalcemia, Skin toxicity... Dose limiting toxicities: Hypercalcemia (grade 4, 22.2%) Sources: Page: p.897Skin toxicity (grade 3, 33.3%) Anemia (grade 3, 11.1%) Thrombocytopenia (grade 3, 11.1%) Emesis (grade 3, 11.1%) Hypercalcemia (grade 3, 11.1%) |
80 mg/m2 2 times / day multiple, oral MTD Dose: 80 mg/m2, 2 times / day Route: oral Route: multiple Dose: 80 mg/m2, 2 times / day Sources: Page: p.897 |
unhealthy, 4 n = 23 Health Status: unhealthy Condition: Neuroblastoma Age Group: 4 Sex: M+F Population Size: 23 Sources: Page: p.897 |
DLT: Hypercalcemia, Skin toxicity... Dose limiting toxicities: Hypercalcemia (grade 4, 4.3%) Sources: Page: p.897Skin toxicity (grade 3, 17.4%) Emesis (grade 3, 4.3%) AST/ALT ratio abnormal (grade 3, 4.3%) |
80 mg/m2 2 times / day multiple, oral MTD Dose: 80 mg/m2, 2 times / day Route: oral Route: multiple Dose: 80 mg/m2, 2 times / day Sources: Page: p.34 |
unhealthy, 4 n = 16 Health Status: unhealthy Condition: Neuroblastoma Age Group: 4 Sex: M+F Population Size: 16 Sources: Page: p.34 |
|
1 mg/kg 2 times / day multiple, oral Recommended Dose: 1 mg/kg, 2 times / day Route: oral Route: multiple Dose: 1 mg/kg, 2 times / day Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Acne Sources: Page: p.1 |
Disc. AE: Fetal damage... AEs leading to discontinuation/dose reduction: Fetal damage (grade 4) Sources: Page: p.1 |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Cheilitis | Disc. AE | 12.5 mg/kg single, oral Overdose Dose: 12.5 mg/kg Route: oral Route: single Dose: 12.5 mg/kg Sources: Page: p.348 |
unhealthy, 29 n = 1 Health Status: unhealthy Condition: Acne Age Group: 29 Sex: M Population Size: 1 Sources: Page: p.348 |
Desquamation | Disc. AE | 12.5 mg/kg single, oral Overdose Dose: 12.5 mg/kg Route: oral Route: single Dose: 12.5 mg/kg Sources: Page: p.348 |
unhealthy, 29 n = 1 Health Status: unhealthy Condition: Acne Age Group: 29 Sex: M Population Size: 1 Sources: Page: p.348 |
Headache | Disc. AE | 12.5 mg/kg single, oral Overdose Dose: 12.5 mg/kg Route: oral Route: single Dose: 12.5 mg/kg Sources: Page: p.348 |
unhealthy, 29 n = 1 Health Status: unhealthy Condition: Acne Age Group: 29 Sex: M Population Size: 1 Sources: Page: p.348 |
Skin xerosis | Disc. AE | 12.5 mg/kg single, oral Overdose Dose: 12.5 mg/kg Route: oral Route: single Dose: 12.5 mg/kg Sources: Page: p.348 |
unhealthy, 29 n = 1 Health Status: unhealthy Condition: Acne Age Group: 29 Sex: M Population Size: 1 Sources: Page: p.348 |
Skin xerosis | Disc. AE | 12.5 mg/kg single, oral Overdose Dose: 12.5 mg/kg Route: oral Route: single Dose: 12.5 mg/kg Sources: Page: p.348 |
unhealthy, 29 n = 1 Health Status: unhealthy Condition: Acne Age Group: 29 Sex: M Population Size: 1 Sources: Page: p.348 |
Diarrhea | Disc. AE | 1000 mg single, oral Overdose Dose: 1000 mg Route: oral Route: single Dose: 1000 mg Sources: Page: p.74 |
unhealthy, 31 n = 1 Health Status: unhealthy Condition: AIDS Age Group: 31 Sex: M Population Size: 1 Sources: Page: p.74 |
Anemia | grade 3, 11.1% DLT |
100 mg/m2 2 times / day multiple, oral Highest studied dose Dose: 100 mg/m2, 2 times / day Route: oral Route: multiple Dose: 100 mg/m2, 2 times / day Sources: Page: p.897 |
unhealthy, 4 n = 9 Health Status: unhealthy Condition: Neuroblastoma Age Group: 4 Sex: M+F Population Size: 9 Sources: Page: p.897 |
Emesis | grade 3, 11.1% DLT |
100 mg/m2 2 times / day multiple, oral Highest studied dose Dose: 100 mg/m2, 2 times / day Route: oral Route: multiple Dose: 100 mg/m2, 2 times / day Sources: Page: p.897 |
unhealthy, 4 n = 9 Health Status: unhealthy Condition: Neuroblastoma Age Group: 4 Sex: M+F Population Size: 9 Sources: Page: p.897 |
Hypercalcemia | grade 3, 11.1% DLT |
100 mg/m2 2 times / day multiple, oral Highest studied dose Dose: 100 mg/m2, 2 times / day Route: oral Route: multiple Dose: 100 mg/m2, 2 times / day Sources: Page: p.897 |
unhealthy, 4 n = 9 Health Status: unhealthy Condition: Neuroblastoma Age Group: 4 Sex: M+F Population Size: 9 Sources: Page: p.897 |
Thrombocytopenia | grade 3, 11.1% DLT |
100 mg/m2 2 times / day multiple, oral Highest studied dose Dose: 100 mg/m2, 2 times / day Route: oral Route: multiple Dose: 100 mg/m2, 2 times / day Sources: Page: p.897 |
unhealthy, 4 n = 9 Health Status: unhealthy Condition: Neuroblastoma Age Group: 4 Sex: M+F Population Size: 9 Sources: Page: p.897 |
Skin toxicity | grade 3, 33.3% DLT |
100 mg/m2 2 times / day multiple, oral Highest studied dose Dose: 100 mg/m2, 2 times / day Route: oral Route: multiple Dose: 100 mg/m2, 2 times / day Sources: Page: p.897 |
unhealthy, 4 n = 9 Health Status: unhealthy Condition: Neuroblastoma Age Group: 4 Sex: M+F Population Size: 9 Sources: Page: p.897 |
Hypercalcemia | grade 4, 22.2% DLT |
100 mg/m2 2 times / day multiple, oral Highest studied dose Dose: 100 mg/m2, 2 times / day Route: oral Route: multiple Dose: 100 mg/m2, 2 times / day Sources: Page: p.897 |
unhealthy, 4 n = 9 Health Status: unhealthy Condition: Neuroblastoma Age Group: 4 Sex: M+F Population Size: 9 Sources: Page: p.897 |
Skin toxicity | grade 3, 17.4% DLT |
80 mg/m2 2 times / day multiple, oral MTD Dose: 80 mg/m2, 2 times / day Route: oral Route: multiple Dose: 80 mg/m2, 2 times / day Sources: Page: p.897 |
unhealthy, 4 n = 23 Health Status: unhealthy Condition: Neuroblastoma Age Group: 4 Sex: M+F Population Size: 23 Sources: Page: p.897 |
AST/ALT ratio abnormal | grade 3, 4.3% DLT |
80 mg/m2 2 times / day multiple, oral MTD Dose: 80 mg/m2, 2 times / day Route: oral Route: multiple Dose: 80 mg/m2, 2 times / day Sources: Page: p.897 |
unhealthy, 4 n = 23 Health Status: unhealthy Condition: Neuroblastoma Age Group: 4 Sex: M+F Population Size: 23 Sources: Page: p.897 |
Emesis | grade 3, 4.3% DLT |
80 mg/m2 2 times / day multiple, oral MTD Dose: 80 mg/m2, 2 times / day Route: oral Route: multiple Dose: 80 mg/m2, 2 times / day Sources: Page: p.897 |
unhealthy, 4 n = 23 Health Status: unhealthy Condition: Neuroblastoma Age Group: 4 Sex: M+F Population Size: 23 Sources: Page: p.897 |
Hypercalcemia | grade 4, 4.3% DLT |
80 mg/m2 2 times / day multiple, oral MTD Dose: 80 mg/m2, 2 times / day Route: oral Route: multiple Dose: 80 mg/m2, 2 times / day Sources: Page: p.897 |
unhealthy, 4 n = 23 Health Status: unhealthy Condition: Neuroblastoma Age Group: 4 Sex: M+F Population Size: 23 Sources: Page: p.897 |
Fetal damage | grade 4 Disc. AE |
1 mg/kg 2 times / day multiple, oral Recommended Dose: 1 mg/kg, 2 times / day Route: oral Route: multiple Dose: 1 mg/kg, 2 times / day Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Acne Sources: Page: p.1 |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
yes [IC50 26.8 uM] | ||||
yes [IC50 76.5 uM] | ||||
yes | ||||
Sources: https://pubmed.ncbi.nlm.nih.gov/25039756/ |
yes | |||
yes | ||||
yes | ||||
Sources: https://pubmed.ncbi.nlm.nih.gov/25039756/ |
yes | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/25039756/ |
yes |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
major | ||||
minor | ||||
minor | ||||
minor | ||||
minor | ||||
minor | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
yes | ||||
yes | ||||
yes | ||||
yes | ||||
yes |
PubMed
Title | Date | PubMed |
---|---|---|
Generation of radical oxygen species by neural crest cells treated in vitro with isotretinoin and 4-oxo-isotretinoin. | 1990 |
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Taste and olfactory disturbances after treatment for acne with isotretinoin, a 13-cis-isomer of retinoic acid. | 1990 |
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Acute depression from isotretinoin. | 1990 Jun |
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[Acne fulminans triggered by isotretinoin therapy]. | 1991 |
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Acute depression from isotretinoin. | 1991 Jul |
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Improvement of scleromyxedema associated with isotretinoin therapy. | 1991 May |
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Fatty liver following isotretinoin therapy. | 1991 May |
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[Successful use of isotretinoin in type Zumbusch generalized pustular psoriasis following recovered etretinate-induced hepatitis]. | 1991 Sep |
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Two new adverse effects of isotretinoin. | 2003 Mar |
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Isotretinoin and antidepressant pharmacotherapy: a prescription sequence symmetry analysis. | 2003 Sep |
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13-cis Retinoic acid ameliorates benzoyl peroxide-induced oxidative stress and hyperproliferative response in murine skin: a chemopreventive study. | 2004 |
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A pilot study evaluating anxiety and depressive scores in acne patients treated with isotretinoin. | 2004 Jun |
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Isotretinoin-associated intracranial hypertension. | 2004 Jun |
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Hypersomnia associated with isotretinoin in a patient with recurrent major depressive disorder and acne vulgaris. | 2004 Jun 15 |
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Isotretinoin (Ro-Accutane) teratogenesis. A case report. | 2005 |
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The detection of differentiation-inducing chemicals by using green fluorescent protein expression in genetically engineered teratocarcinoma cells. | 2005 Apr |
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Treatment of photoaged skin with a cream containing 0.05% isotretinoin and sunscreens. | 2005 Apr |
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Isotretinoin (13-cis-retinoic acid) associated atrial tachycardia. | 2005 Apr |
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[Receptor-related mechanism of proliferation inhibilion and apoptosis induetion of human tongue squamous cell line Tca8113 by retinoids]. | 2005 Aug |
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Retinoic acid and its 4-oxo metabolites are functionally active in human skin cells in vitro. | 2005 Jul |
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13-cis retinoic acid inhibits development and progression of chronic allograft nephropathy. | 2005 Jul |
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Expression of gastrointestinal glutathione peroxidase is inversely correlated to the presence of hepatitis C virus subgenomic RNA in human liver cells. | 2005 Mar 11 |
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Isotretinoin therapy and mood changes in adolescents with moderate to severe acne: a cohort study. | 2005 May |
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Inhibitors of the arachidonic acid pathway and peroxisome proliferator-activated receptor ligands have superadditive effects on lung cancer growth inhibition. | 2005 May 15 |
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Apoptotic events induced by naturally occurring retinoids ATRA and 13-cis retinoic acid on human hepatoma cell lines Hep3B and HepG2. | 2005 Nov 18 |
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Serum levels of albumin, triglycerides, total protein and glucose in rats are altered after oral treatment with low doses of 13-cis-retinoic acid or all-trans-retinoic acid. | 2005 Nov-Dec |
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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 |
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Mechanism of retinoid receptors in inhibiting proliferation and inducing apoptosis of human melanoma cell line A375. | 2005 Sep 5 |
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Differential regulation of Toll-like receptor and CD14 pathways by retinoids and corticosteroids in human sebocytes. | 2006 |
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Low-dose isotretinoin in the treatment of acne vulgaris. | 2006 Apr |
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Increased use of mental health services related to isotretinoin treatment: a 5-year analysis. | 2006 Aug |
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[Panic attacks in a patient treated with isotretinoin for acne. Report of one case]. | 2006 Dec |
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[Mechanism of receptor for retinoids inducing apoptosis of human melanoma cell line A375]. | 2006 Jul |
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A rare side-effect of systemic isotretinoin treatment: hoarseness. | 2006 Nov |
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13 Cis-retinoic acid mediates apoptosis in Dalton's lymphoma ascites cells by regulating gene expression. | 2007 |
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Acneiform eruptions associated with epidermal growth factor receptor-targeted chemotherapy. | 2007 Mar |
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13 cis-retinoic acid regulates cytokine production and inhibits angiogenesis by disrupting endothelial cell migration and tube formation. | 2008 |
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Isotretinoin and the risk of depression in patients with acne vulgaris: a case-crossover study. | 2008 Apr |
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Hypercalcemia induced by 13 cis-retinoic acid in patients with neuroblastoma. | 2008 Apr |
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Use of oral isotretinoin in photoaging therapy. | 2008 Jan-Feb |
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[Isotretinoin embryopathy. Report of one case]. | 2008 Jun |
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Enhanced ocular isotretinoin toxicity in mitochondrial disorder. | 2008 Jun |
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Hypercalcemia and 13-cis-retinoic acid in post-consolidation therapy of neuroblastoma. | 2009 Feb |
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Different mRNA expression profiling of nuclear retinoid, thyroid, estrogen and PPARgamma receptors, their coregulators and selected genes in rat liver and spleen in response to short-term in vivo administration of 13-cis retinoic acid. | 2009 Jan 30 |
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Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. | 2009 May |
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Changes of psychiatric parameters and their relationships by oral isotretinoin in acne patients. | 2009 May |
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Hypercalcemia and osteoblastic lesions induced by 13-Cis-retinoic acid mimicking relapsed neuroblastoma. | 2009 Oct |
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Retinoids activate RXR/CAR-mediated pathway and induce CYP3A. | 2010 Jan 15 |
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Psychiatric reactions to isotretinoin in patients with bipolar disorder. | 2010 May |
|
Chemical genomics profiling of environmental chemical modulation of human nuclear receptors. | 2011 Aug |
Patents
Sample Use Guides
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:
Other
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/16456186
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.
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Classification Tree | Code System | Code | ||
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WHO-ATC |
D11AX19
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WHO-VATC |
QL01XX22
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WHO-VATC |
QD11AH04
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NDF-RT |
N0000007700
Created by
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NCI_THESAURUS |
C804
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NDF-RT |
N0000007700
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FDA ORPHAN DRUG |
101296
Created by
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WHO-ATC |
D11AH04
Created by
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EMA ASSESSMENT REPORTS |
PANRETIN (AUTHORIZED: SARCOMA, KAPOSI)
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NDF-RT |
N0000007700
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NDF-RT |
N0000007700
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FDA ORPHAN DRUG |
110998
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WHO-ATC |
L01XX22
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NDF-RT |
N0000175607
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FDA ORPHAN DRUG |
66592
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NDF-RT |
N0000007700
Created by
admin on Sat Dec 16 17:57:56 GMT 2023 , Edited by admin on Sat Dec 16 17:57:56 GMT 2023
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FDA ORPHAN DRUG |
708819
Created by
admin on Sat Dec 16 17:57:56 GMT 2023 , Edited by admin on Sat Dec 16 17:57:56 GMT 2023
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Code System | Code | Type | Description | ||
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C1574
Created by
admin on Sat Dec 16 17:57:56 GMT 2023 , Edited by admin on Sat Dec 16 17:57:56 GMT 2023
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PRIMARY | |||
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7781
Created by
admin on Sat Dec 16 17:57:56 GMT 2023 , Edited by admin on Sat Dec 16 17:57:56 GMT 2023
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PRIMARY | |||
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7186
Created by
admin on Sat Dec 16 17:57:56 GMT 2023 , Edited by admin on Sat Dec 16 17:57:56 GMT 2023
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PRIMARY | |||
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CHEMBL705
Created by
admin on Sat Dec 16 17:57:56 GMT 2023 , Edited by admin on Sat Dec 16 17:57:56 GMT 2023
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PRIMARY | |||
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m1511
Created by
admin on Sat Dec 16 17:57:56 GMT 2023 , Edited by admin on Sat Dec 16 17:57:56 GMT 2023
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PRIMARY | Merck Index | ||
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3862
Created by
admin on Sat Dec 16 17:57:56 GMT 2023 , Edited by admin on Sat Dec 16 17:57:56 GMT 2023
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PRIMARY | |||
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m9558
Created by
admin on Sat Dec 16 17:57:56 GMT 2023 , Edited by admin on Sat Dec 16 17:57:56 GMT 2023
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PRIMARY | |||
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C103303
Created by
admin on Sat Dec 16 17:57:56 GMT 2023 , Edited by admin on Sat Dec 16 17:57:56 GMT 2023
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PRIMARY | |||
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1UA8E65KDZ
Created by
admin on Sat Dec 16 17:57:56 GMT 2023 , Edited by admin on Sat Dec 16 17:57:56 GMT 2023
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PRIMARY | |||
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DTXSID6040404
Created by
admin on Sat Dec 16 17:57:56 GMT 2023 , Edited by admin on Sat Dec 16 17:57:56 GMT 2023
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PRIMARY | |||
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100000089387
Created by
admin on Sat Dec 16 17:57:56 GMT 2023 , Edited by admin on Sat Dec 16 17:57:56 GMT 2023
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PRIMARY | |||
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5300-03-8
Created by
admin on Sat Dec 16 17:57:56 GMT 2023 , Edited by admin on Sat Dec 16 17:57:56 GMT 2023
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PRIMARY | |||
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DB00523
Created by
admin on Sat Dec 16 17:57:56 GMT 2023 , Edited by admin on Sat Dec 16 17:57:56 GMT 2023
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PRIMARY | |||
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81864
Created by
admin on Sat Dec 16 17:57:56 GMT 2023 , Edited by admin on Sat Dec 16 17:57:56 GMT 2023
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PRIMARY | RxNorm | ||
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KK-22
Created by
admin on Sat Dec 16 17:57:56 GMT 2023 , Edited by admin on Sat Dec 16 17:57:56 GMT 2023
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PRIMARY | |||
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2645
Created by
admin on Sat Dec 16 17:57:56 GMT 2023 , Edited by admin on Sat Dec 16 17:57:56 GMT 2023
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PRIMARY | |||
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ALITRETINOIN
Created by
admin on Sat Dec 16 17:57:56 GMT 2023 , Edited by admin on Sat Dec 16 17:57:56 GMT 2023
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PRIMARY | |||
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659772
Created by
admin on Sat Dec 16 17:57:56 GMT 2023 , Edited by admin on Sat Dec 16 17:57:56 GMT 2023
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PRIMARY | |||
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SUB00344MIG
Created by
admin on Sat Dec 16 17:57:56 GMT 2023 , Edited by admin on Sat Dec 16 17:57:56 GMT 2023
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PRIMARY | |||
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449171
Created by
admin on Sat Dec 16 17:57:56 GMT 2023 , Edited by admin on Sat Dec 16 17:57:56 GMT 2023
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PRIMARY | |||
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50648
Created by
admin on Sat Dec 16 17:57:56 GMT 2023 , Edited by admin on Sat Dec 16 17:57:56 GMT 2023
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PRIMARY | |||
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1UA8E65KDZ
Created by
admin on Sat Dec 16 17:57:56 GMT 2023 , Edited by admin on Sat Dec 16 17:57:56 GMT 2023
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PRIMARY |
ACTIVE MOIETY