Details
Stereochemistry | ACHIRAL |
Molecular Formula | C20H28O2 |
Molecular Weight | 300.4359 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 4 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
C/C(=C(/[H])\C(\[H])=C(/[H])\C(=C(/[H])\C(=O)O)\C)/C(/[H])=C(\[H])/C1=C(C)CCCC1(C)C
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+
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.
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL2363069 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16456186 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
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 Date5.6764801E10 |
|||
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 Date1.18247037E12 |
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 |
---|---|---|
[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
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.
Name | Type | Language | ||
---|---|---|---|---|
|
Official Name | English | ||
|
Common Name | English | ||
|
Brand Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Brand Name | English | ||
|
Brand Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Brand Name | English | ||
|
Common Name | English | ||
|
Official Name | English | ||
|
Brand Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Code | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Brand Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Brand Name | English | ||
|
Common Name | English | ||
|
Brand Name | English | ||
|
Brand Name | English | ||
|
Brand Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Brand Name | English | ||
|
Brand Name | English | ||
|
Common Name | English |
Classification Tree | Code System | Code | ||
---|---|---|---|---|
|
NDF-RT |
N0000007700
Created by
admin on Fri Jun 25 20:57:59 UTC 2021 , Edited by admin on Fri Jun 25 20:57:59 UTC 2021
|
||
|
NDF-RT |
N0000175607
Created by
admin on Fri Jun 25 20:57:59 UTC 2021 , Edited by admin on Fri Jun 25 20:57:59 UTC 2021
|
||
|
NCI_THESAURUS |
C68299
Created by
admin on Fri Jun 25 20:57:59 UTC 2021 , Edited by admin on Fri Jun 25 20:57:59 UTC 2021
|
||
|
WHO-VATC |
QL01XX14
Created by
admin on Fri Jun 25 20:57:59 UTC 2021 , Edited by admin on Fri Jun 25 20:57:59 UTC 2021
|
||
|
FDA ORPHAN DRUG |
71692
Created by
admin on Fri Jun 25 20:57:59 UTC 2021 , Edited by admin on Fri Jun 25 20:57:59 UTC 2021
|
||
|
NCI_THESAURUS |
C804
Created by
admin on Fri Jun 25 20:57:59 UTC 2021 , Edited by admin on Fri Jun 25 20:57:59 UTC 2021
|
||
|
FDA ORPHAN DRUG |
5785
Created by
admin on Fri Jun 25 20:57:59 UTC 2021 , Edited by admin on Fri Jun 25 20:57:59 UTC 2021
|
||
|
FDA ORPHAN DRUG |
165802
Created by
admin on Fri Jun 25 20:57:59 UTC 2021 , Edited by admin on Fri Jun 25 20:57:59 UTC 2021
|
||
|
LOINC |
87673-0
Created by
admin on Fri Jun 25 20:57:59 UTC 2021 , Edited by admin on Fri Jun 25 20:57:59 UTC 2021
|
||
|
WHO-VATC |
QD10AD51
Created by
admin on Fri Jun 25 20:57:59 UTC 2021 , Edited by admin on Fri Jun 25 20:57:59 UTC 2021
|
||
|
FDA ORPHAN DRUG |
50990
Created by
admin on Fri Jun 25 20:57:59 UTC 2021 , Edited by admin on Fri Jun 25 20:57:59 UTC 2021
|
||
|
WHO-ATC |
D10AD51
Created by
admin on Fri Jun 25 20:57:59 UTC 2021 , Edited by admin on Fri Jun 25 20:57:59 UTC 2021
|
||
|
NDF-RT |
N0000007700
Created by
admin on Fri Jun 25 20:57:59 UTC 2021 , Edited by admin on Fri Jun 25 20:57:59 UTC 2021
|
||
|
NDF-RT |
N0000007700
Created by
admin on Fri Jun 25 20:57:59 UTC 2021 , Edited by admin on Fri Jun 25 20:57:59 UTC 2021
|
||
|
WHO-ATC |
D10AD01
Created by
admin on Fri Jun 25 20:57:59 UTC 2021 , Edited by admin on Fri Jun 25 20:57:59 UTC 2021
|
||
|
WHO-VATC |
QD10AD01
Created by
admin on Fri Jun 25 20:57:59 UTC 2021 , Edited by admin on Fri Jun 25 20:57:59 UTC 2021
|
||
|
WHO-ATC |
L01XX14
Created by
admin on Fri Jun 25 20:57:59 UTC 2021 , Edited by admin on Fri Jun 25 20:57:59 UTC 2021
|
||
|
NDF-RT |
N0000007700
Created by
admin on Fri Jun 25 20:57:59 UTC 2021 , Edited by admin on Fri Jun 25 20:57:59 UTC 2021
|
||
|
NDF-RT |
N0000007700
Created by
admin on Fri Jun 25 20:57:59 UTC 2021 , Edited by admin on Fri Jun 25 20:57:59 UTC 2021
|
||
|
LIVERTOX |
993
Created by
admin on Fri Jun 25 20:57:59 UTC 2021 , Edited by admin on Fri Jun 25 20:57:59 UTC 2021
|
Code System | Code | Type | Description | ||
---|---|---|---|---|---|
|
CHEMBL38
Created by
admin on Fri Jun 25 20:57:59 UTC 2021 , Edited by admin on Fri Jun 25 20:57:59 UTC 2021
|
PRIMARY | |||
|
2722
Created by
admin on Fri Jun 25 20:57:59 UTC 2021 , Edited by admin on Fri Jun 25 20:57:59 UTC 2021
|
PRIMARY | |||
|
M9558
Created by
admin on Fri Jun 25 20:57:59 UTC 2021 , Edited by admin on Fri Jun 25 20:57:59 UTC 2021
|
PRIMARY | Merck Index | ||
|
2875
Created by
admin on Fri Jun 25 20:57:59 UTC 2021 , Edited by admin on Fri Jun 25 20:57:59 UTC 2021
|
PRIMARY | |||
|
444795
Created by
admin on Fri Jun 25 20:57:59 UTC 2021 , Edited by admin on Fri Jun 25 20:57:59 UTC 2021
|
PRIMARY | |||
|
5688UTC01R
Created by
admin on Fri Jun 25 20:57:59 UTC 2021 , Edited by admin on Fri Jun 25 20:57:59 UTC 2021
|
PRIMARY | |||
|
221175
Created by
admin on Fri Jun 25 20:57:59 UTC 2021 , Edited by admin on Fri Jun 25 20:57:59 UTC 2021
|
ALTERNATIVE | |||
|
C900
Created by
admin on Fri Jun 25 20:57:59 UTC 2021 , Edited by admin on Fri Jun 25 20:57:59 UTC 2021
|
PRIMARY | |||
|
TRETINOIN
Created by
admin on Fri Jun 25 20:57:59 UTC 2021 , Edited by admin on Fri Jun 25 20:57:59 UTC 2021
|
PRIMARY | |||
|
10753
Created by
admin on Fri Jun 25 20:57:59 UTC 2021 , Edited by admin on Fri Jun 25 20:57:59 UTC 2021
|
PRIMARY | |||
|
DB00755
Created by
admin on Fri Jun 25 20:57:59 UTC 2021 , Edited by admin on Fri Jun 25 20:57:59 UTC 2021
|
PRIMARY | |||
|
Tretinoin
Created by
admin on Fri Jun 25 20:57:59 UTC 2021 , Edited by admin on Fri Jun 25 20:57:59 UTC 2021
|
PRIMARY | |||
|
302-79-4
Created by
admin on Fri Jun 25 20:57:59 UTC 2021 , Edited by admin on Fri Jun 25 20:57:59 UTC 2021
|
PRIMARY | |||
|
2644
Created by
admin on Fri Jun 25 20:57:59 UTC 2021 , Edited by admin on Fri Jun 25 20:57:59 UTC 2021
|
PRIMARY | |||
|
2169
Created by
admin on Fri Jun 25 20:57:59 UTC 2021 , Edited by admin on Fri Jun 25 20:57:59 UTC 2021
|
PRIMARY | |||
|
SUB11246MIG
Created by
admin on Fri Jun 25 20:57:59 UTC 2021 , Edited by admin on Fri Jun 25 20:57:59 UTC 2021
|
PRIMARY | |||
|
302-79-4
Created by
admin on Fri Jun 25 20:57:59 UTC 2021 , Edited by admin on Fri Jun 25 20:57:59 UTC 2021
|
PRIMARY | |||
|
1674004
Created by
admin on Fri Jun 25 20:57:59 UTC 2021 , Edited by admin on Fri Jun 25 20:57:59 UTC 2021
|
PRIMARY | USP-RS | ||
|
206-129-0
Created by
admin on Fri Jun 25 20:57:59 UTC 2021 , Edited by admin on Fri Jun 25 20:57:59 UTC 2021
|
PRIMARY | |||
|
D014212
Created by
admin on Fri Jun 25 20:57:59 UTC 2021 , Edited by admin on Fri Jun 25 20:57:59 UTC 2021
|
PRIMARY |
ACTIVE MOIETY
METABOLITE (PARENT)
METABOLITE (PARENT)
METABOLITE (PARENT)
METABOLITE (PARENT)
PARENT (METABOLITE)
SALT/SOLVATE (PARENT)