3,7-dimethyl-9-(2,6,6-trimethylcyclohex-1-en-1-yl)nona-2,4,6,8-tetraenoic acid

• ChemBase ID: 635
• Molecular Formular: C20H28O2
• Molecular Mass: 300.43512
• Monoisotopic Mass: 300.20893014
• SMILES: OC(=O)C=C(C=CC=C(C=CC1=C(CCCC1(C)C)C)C)C
• Canonical SMILES: CC(=CC=CC(=CC(=O)O)C)C=CC1=C(C)CCCC1(C)C
• InChI: 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)
• InChIKey: SHGAZHPCJJPHSC-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 3,7-dimethyl-9-(2,6,6-trimethylcyclohex-1-en-1-yl)nona-2,4,6,8-tetraenoic acid; (2E,4E,6E,8E)-3,7-dimethyl-9-(2,6,6-trimethylcyclohex-1-en-1-yl)nona-2,4,6,8-tetraenoic acid; (2Z,4E,6E,8E)-3,7-dimethyl-9-(2,6,6-trimethylcyclohex-1-en-1-yl)nona-2,4,6,8-tetraenoic acid; (2E,4Z,6E,8E)-3,7-dimethyl-9-(2,6,6-trimethylcyclohex-1-en-1-yl)nona-2,4,6,8-tetraenoic acid; (2Z,4Z,6E,8E)-3,7-dimethyl-9-(2,6,6-trimethylcyclohex-1-en-1-yl)nona-2,4,6,8-tetraenoic acid; (2Z,4E,6Z,8E)-3,7-dimethyl-9-(2,6,6-trimethylcyclohex-1-en-1-yl)nona-2,4,6,8-tetraenoic acid
• IUPAC Traditional name: tretinoin; isotretinoin; 11-cis-retinoic acid; (2Z,4Z,6E,8E)-3,7-dimethyl-9-(2,6,6-trimethylcyclohex-1-en-1-yl)nona-2,4,6,8-tetraenoic acid; 9,13-di-cis-retinoic acid
• Brand Name: Aberel; Accutane; Airol; Aknefug; Aknoten; Amnesteem; Claravis; Dermairol; Eudyna; Lsotretinoin; Retisol-A; Solage; Sotret; Stieva-A; Stieva-a Forte; Tri-Luma; Vitinoin; Atra-IV; Accutane Roche
• Synonyms: ATRA; Retionic Acid; All Trans-Retinoic Acid; All Trans Retinoic Acid; beta-Retinoic Acid; tretinoin; Tretinoin; (2E,4E,6E,8E)-3,7-Dimethyl-9-(2,6,6-trimethyl-cyclohex-1-en-1-yl)nona-2,4,6,8-tetraenoic acid; RA; Retinoic acid; 13-cis-Retinoic acid; all-trans-Retinoic acid; Retinoic acid; 3,7-Dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-2Z,4E,6E,8E-nonatetranenoic Acid; 13-cis-Vitamin A Acid; Isotrex; IsotrexGel; Neovitamin A Acid; Ro 4-3780; Roaccutan; Roaccutane; (all-E)-3,7-Dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-2,4,6,8-nonatetraenoic Acid; Aberel; Avita; Retinova; 11-cis-Retinoic Acid; 11-cis-Retinoic Acid; (11-cis,13-cis)-Retinoic Acid; 11,13-Di-cis-retinoic Acid; 11-cis,13-cis-Retinoic Acid; all-trans-Retinoic Acid; (9-cis,13-cis)-Retinoic Acid; 9,13-Di-cis-retinoic Acid; 9-cis,13-cis-Retinoic Acid; (2E,4E,6E,8E)-3,7-Dimethyl-9-(2,6,6-trimethylcyclohex-1-en-1-yl)nona-2,4,6,8-tetraenoic acid; Isotretinoin; 13-cis-RETINOIC ACID; Vitamin A acid; RETINOIC ACID ALL trans ISOMER; 9-cis-RETINOIC ACID; Accutane; Amnesteem; Claravis; Sotret; Airol; Renova; Atralin; Retin-A; Av; Vesanoid; Isotretinoin; 视黄酸

Database IDs

• CAS Number: 5300-03-8; 4759-48-2; 5352-74-9; 3555-80-4; 68070-35-9; 302-79-4
• EC Number: 225-296-0; 206-129-0
• MDL Number: MFCD00001551; MFCD00079542
• Beilstein Number: 2057223
• Merck Index: 148165
• PubChem SID: 24278676; 24278674; 160964098; 46504843
• PubChem CID: 444795; 5538
• CHEMBL: 38
• Wikipedia Title: Retinoic_acid

CALCULATED PROPERTIES

JChem

• H Donor: 1
• LogD (pH = 5.5): 4.392896
• LogD (pH = 7.4): 2.6406298
• Log P: 5.0143676
• Molar Refractivity: 97.7908 cm^3
• Polarizability: 36.17498 Å^3
• Polar Surface Area: 37.3 Å^2
• Rotatable Bonds: 5
• Lipinski's Rule of Five: false
• Acid pKa: 4.996648
• H Acceptors: 2

ALOGPS 2.1

• Log P: 5.66
• LOG S: -4.8
• Solubility (Water): 4.77e-03 g/l

PROPERTIES

Physical Property

• Solubility: <0.1 g/100 mL; Acetone; Chloroform; Dimethyl Sulfoxide (25mg/ml); DMSO; Ethanol (25 mg/ml); Ethanol (slightly); Ether; Ethyl Acetate; Isopropanol; Methanol; nearly insoluble in water; soluble in fat
• Apperance: Crystalline; Pale Yellow Solid; yellow powder; yellow to light orange crystalline powder with characteristic floral odor; Yellow-Orange Solid
• Melting Point: 116-120°C; 168-170°C; 172-175 °C(lit.); 176-178°C; 180-181 °C(lit.); 180-182 °C, crystals from ethanol; 180-182°C; 180-182°C; 182-186 °C; 89-92°C
• Hydrophobicity(logP): 4.2

Safety Information

• Storage Condition: 0°C, Desiccate, Protect from light; -20°C; -20°C, Protect from light; -20°C, Store Under Nitrogen, Protect from light; -86°C Freezer, Under Inert Atmosphere; Amber Vial, -20°C Freezer, Under Inert Atmosphere; Amber Vial, -86°C Freezer, Under Inert Atmosphere
• Storage Warning: IRRITANT; Light Sensitive; Moisture, Temperature, Light Sensitive, Store in freezer; Store Dry in Freezer at -20°C for up to 1 year; in Solution
• RTECS: VH6440000; VH6475000
• European Hazard Symbols: Nature polluting (N); Toxic (T); X; Harmful (Xn)
• German water hazard class: 2; 3
• Risk Statements: 22; 22-51/53; 22-63; 61-36/37/38; R:22
• Safety Statements: 36/37; 53-26-36/37/39-45; 61; S:36/37/39
• TSCA Listed: false; 是
• GHS Pictograms: GHS06; GHS07; GHS08; GHS09
• GHS Signal Word: Danger; Warning
• GHS Hazard statements: H301-H361; H302; H302-H411; H315-H319-H335-H360
• GHS Precautionary statements: P201-P261-P305 + P351 + P338-P308 + P313; P273; P281-P301+P310-P321-P308+P313-P405-P501A
• Personal Protective Equipment: dust mask type N95 (US), Eyeshields, Gloves; Eyeshields, full-face particle respirator type N100 (US), Gloves, respirator cartridge type N100 (US), type P1 (EN143) respirator filter, type P3 (EN 143) respirator cartridges
• Storage Temperature: -20°C; 2-8°C

Pharmacology Properties

• Target: hydroxysteroid dehydrogenase
• Gene Information: human ... NOS2(4843), RARA(5914), RARB(5915); human ... RARA(5914), RARB(5915), RARG(5916); human ... RARA(5914), RARB(5915), RARG(5916), RXRA(6256), RXRB(6257), RXRG(6258)mouse ... Rara(19401), Rarb(218772), Rarg(19411), Rxrb(20182)

Product Information

• Purity: >98%; ≥98% (HPLC); ≥98.0% (HPLC); 95+%; 98%
• Salt Data: Free Base
• Ignition Residue: ≤0.1% (as SO4)
• Impurities: ≤0.002% heavy metals
• Loss on Drying: ≤0.5% loss on drying
• Empirical Formula (Hill Notation): C20H28O2

DETAILS

MP Biomedicals - 02158725

Purity: >98%
VDR-RXR heterodimer-DNA complex destabilizer.

MP Biomedicals - 02190269

All Trans Isomer
Crystalline
Reported to inhibit tumor cell proliferation in cultures.

DrugBank - DB00982

• Drug Groups: approved
• Description: Isotretinoin is a medication used for the treatment of severe acne. It is sometimes used in prevention of certain skin cancers. It is a retinoid, meaning it derives from vitamin A and is found in small quantities naturally in the body. Isotretinoin binds to and activates nuclear retinoic acid receptors (RAR), thereby regulating cell proliferation and differentiation. This agent also exhibits immunomodulatory and anti-inflammatory responses and inhibits ornithine decarboxylase, thereby decreasing polyamine synthesis and keratinization.
• Indication: For the treatment of severe recalcitrant nodular acne
• Pharmacology: Isotretinoin, a retinoid, is indicated in 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. Clinical improvement in nodular acne patients occurs in association with a reduction in sebum secretion. The decrease in sebum secretion is temporary and is related to the dose and duration of treatment with Accutane, and reflects a reduction in sebaceous gland size and an inhibition of sebaceous gland differentiation.
• Toxicity: Isotretinoin is teratogenic. It also causes mucocutaneous side effects suck as cheilitis, dry skin, and dry eyes.
• Affected Organisms: Humans and other mammals
• Half Life: 17-50 hours
• Protein Binding: 99.9%
• Elimination: Isotretinoin and its metabolites are further metabolized into conjugates, which are then excreted in urine and feces. The metabolites of isotretinoin and any conjugates are ultimately excreted in the feces and urine in relatively equal amounts (total of 65% to 83%).
• Clearance: * 96 +/- 6.27 L/hr [severe recalcitrant nodular acne pediatric Patients, 12 to 15 Years]
• References: Berard A, Azoulay L, Koren G, Blais L, Perreault S, Oraichi D: Isotretinoin, pregnancies, abortions and birth defects: a population-based perspective. Br J Clin Pharmacol. 2007 Feb;63(2):196-205. [Pubmed] ; Holmes SC, Bankowska U, Mackie RM: The prescription of isotretinoin to women: is every precaution taken? Br J Dermatol. 1998 Mar;138(3):450-5. [Pubmed] ; Amichai B, Shemer A, Grunwald MH: Low-dose isotretinoin in the treatment of acne vulgaris. J Am Acad Dermatol. 2006 Apr;54(4):644-6. [Pubmed] ; Seukeran DC, Cunliffe WJ: Acne vulgaris in the elderly: the response to low-dose isotretinoin. Br J Dermatol. 1998 Jul;139(1):99-101. [Pubmed] ; Tirado Sanchez A, Leon Dorantes G: [Erectile dysfunction during isotretinoin therapy] Actas Urol Esp. 2005 Nov-Dec;29(10):974-6. [Pubmed]
• External Links: Wikipedia; RxList; Drugs.com

DrugBank - DB00755

• Drug Groups: approved; nutraceutical; investigational
• Description: Tretinoin, also known as all-trans-retinoic acid (ATRA), is a naturally occurring derivative of vitamin A (retinol). Retinoids such as tretinoin are important regulators of cell reproduction, proliferation, and differentiation and are used to treat acne and photodamaged skin and to manage keratinization disorders such as ichthyosis and keratosis follicularis. Tretinoin also represents the class of anticancer drugs called differentiating agents and is used in the treatment of acute promyelocytic leukemia (APL).
• Indication: For the the induction of remission in patients with acute promyelocytic leukemia (APL), French-American-British (FAB) classification M3 (including the M3 variant); For the topical treatment of acne vulgaris, flat warts and other skin conditions (psoriasis, ichthyosis congenita, icthyosis vulgaris, lamellar icthyosis, keratosis palmaris et plantaris, epidermolytic hyperkeratosis, senile comedones, senile keratosis, keratosis follicularis (Darier's disease), and basal cell carcinomas.); For palliative therapy to improve fine wrinkling, mottled hyperpigmentation, roughness associated with photodamage.
• Pharmacology: Tretinoin, also known as all-trans-retinoic acid (ATRA), is a naturally occurring derivative of vitamin A (retinol). Retinoids such as tretinoin are important regulators of cell reproduction, proliferation, and differentiation and are used to treat acne and photodamaged skin and to manage keratinization disorders such as ichthyosis and keratosis follicularis. Tretinoin also represents the class of anticancer drugs called differentiating agents and is used in the treatment of acute promyelocytic leukemia (APL).
• Affected Organisms: Humans and other mammals
• Biotransformation: Hepatic
• Absorption: 1-31% (topical)
• Half Life: 0.5-2 hours
• Protein Binding: > 95%
• References: Huang ME, Ye YC, Chen SR, Chai JR, Lu JX, Zhoa L, Gu LJ, Wang ZY: Use of all-trans retinoic acid in the treatment of acute promyelocytic leukemia. Blood. 1988 Aug;72(2):567-72. [Pubmed] ; Castaigne S, Chomienne C, Daniel MT, Ballerini P, Berger R, Fenaux P, Degos L: All-trans retinoic acid as a differentiation therapy for acute promyelocytic leukemia. I. Clinical results. Blood. 1990 Nov 1;76(9):1704-9. [Pubmed] ; Sanz MA: Treatment of acute promyelocytic leukemia. Hematology Am Soc Hematol Educ Program. 2006;:147-55. [Pubmed] ; Mao JT, Goldin JG, Dermand J, Ibrahim G, Brown MS, Emerick A, McNitt-Gray MF, Gjertson DW, Estrada F, Tashkin DP, Roth MD: A pilot study of all-trans-retinoic acid for the treatment of human emphysema. Am J Respir Crit Care Med. 2002 Mar 1;165(5):718-23. [Pubmed] ; Roth MD, Connett JE, D'Armiento JM, Foronjy RF, Friedman PJ, Goldin JG, Louis TA, Mao JT, Muindi JR, O'Connor GT, Ramsdell JW, Ries AL, Scharf SM, Schluger NW, Sciurba FC, Skeans MA, Walter RE, Wendt CH, Wise RA: Feasibility of retinoids for the treatment of emphysema study. Chest. 2006 Nov;130(5):1334-45. [Pubmed]
• External Links: Wikipedia; RxList; Drugs.com

Selleck Chemicals - S1653

Research Area: Cancer
Biological Activity:
Tretinoin is an agent which is commonly used to treat acne vulgaris and keratosis pilaris. Its success in treating acute promyelocytic leukemia was a major breakthrough in the treatment of this type of leukemia. It works in APL because the majority of cases involve a chromosomal translocation of chromosomes 15 and 17, which causes genetic fusion of the retinoic acid receptor (RAR) gene to the promyelocytic leukemia (PML) gene. This fusion PML-RAR protein is responsible for preventing immature myeloid cells from differentiating into more mature cells. [1]

Selleck Chemicals - S1379

Research Area: Acne
Biological Activity:
Isotretinoin is a medication used for the treatment of severe acne. It was first developed to be used as a chemotherapy medication for the treatment of brain cancer, pancreatic cancer and more. It is still used in the treatment of these cancers to this day because of its ability to kill rapidly dividing cells. [1]

Sigma Aldrich - R2625

Frequently Asked Questions
Live Chat and Frequently Asked Questions are available for this Product.
包装
1, 5 g in ampule
50, 100, 500 mg in ampule
Sealed ampule
Biochem/physiol Actions
all-trans-Retinoic acid (ATRA) is a ligand for both the retinoic acid receptor (RAR) and the retinoid X receptor (RXR). The bound RAR and RXR act as transcription factors that regulate the growth and differentiation of both normal and malignant cells. Cytochromes P450 (CYPs) catalyze the 4-hydroxylation of ATRA. Retinoic acid primes embryonic stem cells to become neurons.
Other Notes
Tandem Mass Spectrometry data independently generated by Scripps Center for Metabolomics is available to view or download in PDF. R2625.pdf Tested metabolites are featured on Scripps Center for Metabolomics METLIN Metabolite Database. To learn more, visit sigma.com/metlin.

Sigma Aldrich - R3255

Biochem/physiol Actions
13-cis-Retinoic acid (RA) has anti-inflammatory and anti-tumor action. The action of RA is mediated through RAR-β and RAR-α receptors. RA attenuates iNOS expression and activity in cytokine-stimulated murine mesangial cells. It induces mitochondrial membrane permeability transition, observed as swelling and as a decrease in membrane potential, and stimulates the release of cytochrome c implicating mechanisms through the apoptosis pathway. These activities are reversed by EGTA and cyclosporin A. RA also increases MMP-1 protein expression partially via increased transcription.
Other Notes
Tandem Mass Spectrometry data independently generated by Scripps Center for Metabolomics is available to view or download in PDF. R3255.pdf Tested metabolites are featured on Scripps Center for Metabolomics METLIN Metabolite Database. To learn more, visit sigma.com/metlin.

Sigma Aldrich - 95152

Other Notes
Review: Retinoic acid metabolism1
Unit Definition
1 U corresponds to 1 international U acc. to Ph Eur II, 217 (1983)
Biochem/physiol Actions
all-trans-Retinoic acid (ATRA) is a ligand for both the retinoic acid receptor (RAR) and the retinoid X receptor (RXR). The bound RAR and RXR act as transcription factors that regulate the growth and differentiation of both normal and malignant cells. Cytochromes P450 (CYPs) catalyze the 4-hydroxylation of ATRA. Retinoic acid primes embryonic stem cells to become neurons.

Toronto Research Chemicals - R250200

Physiological metabolite of vitamin A. Effects gene expression via nuclear retinoic acid receptors (RAR); mediates cellular growth and differentiation.

Toronto Research Chemicals - R245015

An endogenous retinoid that induces liver fibrosis via the activation of latent transforming growth factor-β. A major plasma metabolite of 9-cis Retinoic Acid (R245000).

Toronto Research Chemicals - R250000

Used as a treatment for severe acne. Presently being studied in conjuction with the treatment of photoaged skin.

Toronto Research Chemicals - R245020

A retinoid compound with reduced toxicity than the starting or parent retinoid.

Toronto Research Chemicals - R245030

An impurity of Isotretinoin as per European Pharmacopoeia.

REFERENCES

• Cheskis, B. and Freedman, L.P., Mol. Cell. Biol., 14: 3329, (1994).
• Cancer Res. , 40 : 214, (1980).
• Holmes SC, Bankowska U, Mackie RM: The prescription of isotretinoin to women: is every precaution taken? Br J Dermatol. 1998 Mar;138(3):450-5. Pubmed
• Amichai B, Shemer A, Grunwald MH: Low-dose isotretinoin in the treatment of acne vulgaris. J Am Acad Dermatol. 2006 Apr;54(4):644-6. Pubmed
• Seukeran DC, Cunliffe WJ: Acne vulgaris in the elderly: the response to low-dose isotretinoin. Br J Dermatol. 1998 Jul;139(1):99-101. Pubmed
• Tirado Sanchez A, Leon Dorantes G: [Erectile dysfunction during isotretinoin therapy] Actas Urol Esp. 2005 Nov-Dec;29(10):974-6. Pubmed
• Berard A, Azoulay L, Koren G, Blais L, Perreault S, Oraichi D: Isotretinoin, pregnancies, abortions and birth defects: a population-based perspective. Br J Clin Pharmacol. 2007 Feb;63(2):196-205. Pubmed
• Huang ME, Ye YC, Chen SR, Chai JR, Lu JX, Zhoa L, Gu LJ, Wang ZY: Use of all-trans retinoic acid in the treatment of acute promyelocytic leukemia. Blood. 1988 Aug;72(2):567-72. Pubmed
• Castaigne S, Chomienne C, Daniel MT, Ballerini P, Berger R, Fenaux P, Degos L: All-trans retinoic acid as a differentiation therapy for acute promyelocytic leukemia. I. Clinical results. Blood. 1990 Nov 1;76(9):1704-9. Pubmed
• Sanz MA: Treatment of acute promyelocytic leukemia. Hematology Am Soc Hematol Educ Program. 2006;:147-55. Pubmed
• Mao JT, Goldin JG, Dermand J, Ibrahim G, Brown MS, Emerick A, McNitt-Gray MF, Gjertson DW, Estrada F, Tashkin DP, Roth MD: A pilot study of all-trans-retinoic acid for the treatment of human emphysema. Am J Respir Crit Care Med. 2002 Mar 1;165(5):718-23. Pubmed
• Roth MD, Connett JE, D'Armiento JM, Foronjy RF, Friedman PJ, Goldin JG, Louis TA, Mao JT, Muindi JR, O'Connor GT, Ramsdell JW, Ries AL, Scharf SM, Schluger NW, Sciurba FC, Skeans MA, Walter RE, Wendt CH, Wise RA: Feasibility of retinoids for the treatment of emphysema study. Chest. 2006 Nov;130(5):1334-45. Pubmed
• http://en.wikipedia.org/wiki/Tretinoin
• http://en.wikipedia.org/wiki/Isotretinoin
• Kamm, J.J., et al.: J. Am. Acad. Dermatol., 6, 652 (1982)
• Warrel, R.P., et al.: Leukemia, 8, 929 (1982)
• Sasai, Y., et al.: J. Neurol., 249, 41 (1982)
• Okuno, M. et al.: Kanxo, 39, 224 (1998)
• Nagase, S.: Gidu Gaig. Igak. Kiyo, 47, 25 (1998)
• Tzimas, G. et al.: Drug Metab. Disp., 22, 928 (1998)
• Horst, R.L. et al.: Biochemistry, 34, 1203 (1998)
• Lerche, C., et al.: Exp. Dermatol., 17, 972 (2008)
• Sato, T., et al.: J. Med. Chem., 51, 7705 (2008)
• Gan, J., et al.: Chem. Res. Toxicol., 22, 690 (2008)
• Macejova, D., et al.: Toxicol. Lett., 184, 114 (2008)
• Chen, P., et al.: Toxicol. App. Pharmacol.,
• Carter, H.E., et al.: J. Biol. Chem., 175, 683 (1943)
• Munoz-Botella, S., et al.: J. Pharm. Biomed. Anal., 14, 909 (1996)
• Proksa, B., et al.: Anal. Chim. Acta, 434, 75 (1996)