4-[1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)ethenyl]benzoic acid

• ChemBase ID: 192
• Molecular Formular: C24H28O2
• Molecular Mass: 348.47792
• Monoisotopic Mass: 348.20893014
• SMILES: OC(=O)c1ccc(C(=C)c2cc3C(CCC(c3cc2C)(C)C)(C)C)cc1
• Canonical SMILES: Cc1cc2c(cc1C(=C)c1ccc(cc1)C(=O)O)C(C)(C)CCC2(C)C
• InChI: InChI=1S/C24H28O2/c1-15-13-20-21(24(5,6)12-11-23(20,3)4)14-19(15)16(2)17-7-9-18(10-8-17)22(25)26/h7-10,13-14H,2,11-12H2,1,3-6H3,(H,25,26)
• InChIKey: NAVMQTYZDKMPEU-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 4-[1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)ethenyl]benzoic acid
• IUPAC Traditional name: bexarotene; targretin
• Brand Name: Targret; Targretin; Targretyn; Targrexin; Targretin-gel
• Synonyms: 4-[1-(5,6,7,8-Tetrahydro-3,5,5,8,8-pentamethyl-2-naphthalenyl)ethenyl)benzoic Acid; LG 100069; LG 1069; LG 69; LGD 1069; RO 26-4455; SR 11247; Targret; Targretin; Targretyn; Targrexin; bexarotene; Bexarotene

Database IDs

• CAS Number: 153559-49-0
• PubChem SID: 46509119; 160963655
• PubChem CID: 82146

CALCULATED PROPERTIES

JChem

• Acid pKa: 4.0707927
• H Acceptors: 2
• H Donor: 1
• LogD (pH = 5.5): 5.4988923
• LogD (pH = 7.4): 3.8234684
• Log P: 6.9405375
• Molar Refractivity: 117.124 cm^3
• Polarizability: 41.398285 Å^3
• Polar Surface Area: 37.3 Å^2
• Rotatable Bonds: 3
• Lipinski's Rule of Five: false

ALOGPS 2.1

• Log P: 6.86
• LOG S: -6.37
• Solubility (Water): 1.49e-04 g/l

PROPERTIES

Physical Property

• Solubility: Chloroform; Methanol
• Apperance: White Solid
• Melting Point: 230-231°C
• Hydrophobicity(logP): 6.9

Safety Information

• Storage Condition: -20°C Freezer

Pharmacology Properties

• Target: Others

Product Information

• Salt Data: Free Base

DETAILS

DrugBank - DB00307

• Drug Groups: approved; investigational
• Description: Bexarotene (Targretin) is an antineoplastic agent indicated by the FDA for Cutaneous T cell lymphoma. It has been used off-label for lung cancer, breast cancer, and Kaposi's sarcoma. [Wikipedia]
• Indication: Used orally for the treatment of skin manifestations of cutaneous T-cell lymphoma (CTCL) in patients who are refractory to at least one prior systemic therapy. Also used topically for the treatment of skin lesions in early (stage IA and IB) CTCL in patients who experience refractory or persistent disease with the use of other therapies or are intolerant of other therapies.
• Pharmacology: Bexarotene is a member of a subclass of retinoids that selectively activate retinoid X receptors (RXRs). These retinoid receptors have biologic activity distinct from that of retinoic acid receptors (RARs). Bexarotene is indicated for the treatment of cutaneous manifestations of cutaneous T-cell lymphoma in patients who are refractory to at least one prior systemic therapy. Bexarotene selectively binds and activates retinoid X receptor subtypes (RXR_α, RXR_β, RXR_γ). RXRs can form heterodimers with various receptor partners such as retinoic acid receptors (RARs), vitamin D receptor, thyroid receptor, and peroxisome proliferator activator receptors (PPARs). Once activated, these receptors function as transcription factors that regulate the expression of genes that control cellular differentiation and proliferation. Bexarotene inhibits the growth in vitro of some tumor cell lines of hematopoietic and squamous cell origin. It also induces tumor regression in vivo in some animal models.
• Affected Organisms: Humans and other mammals
• Half Life: 7 hours
• Protein Binding: >99%
• Elimination: Urinary elimination of bexarotene and its known metabolites is a minor excretory pathway (<1% of administered dose).
• References: Gniadecki R, Assaf C, Bagot M, Dummer R, Duvic M, Knobler R, Ranki A, Schwandt P, Whittaker S: The optimal use of bexarotene in cutaneous T-cell lymphoma. Br J Dermatol. 2007 Sep;157(3):433-40. Epub 2007 Jun 6. [Pubmed] ; Dragnev KH, Petty WJ, Shah SJ, Lewis LD, Black CC, Memoli V, Nugent WC, Hermann T, Negro-Vilar A, Rigas JR, Dmitrovsky E: A proof-of-principle clinical trial of bexarotene in patients with non-small cell lung cancer. Clin Cancer Res. 2007 Mar 15;13(6):1794-800. [Pubmed] ; Smit JW, Stokkel MP, Pereira AM, Romijn JA, Visser TJ: Bexarotene-induced hypothyroidism: bexarotene stimulates the peripheral metabolism of thyroid hormones. J Clin Endocrinol Metab. 2007 Jul;92(7):2496-9. Epub 2007 Apr 17. [Pubmed] ; Lowe MN, Plosker GL: Bexarotene. Am J Clin Dermatol. 2000 Jul-Aug;1(4):245-50; discussion 251-2. [Pubmed] ; Yen WC, Prudente RY, Corpuz MR, Negro-Vilar A, Lamph WW: A selective retinoid X receptor agonist bexarotene (LGD1069, targretin) inhibits angiogenesis and metastasis in solid tumours. Br J Cancer. 2006 Mar 13;94(5):654-60. [Pubmed] ; Farol LT, Hymes KB: Bexarotene: a clinical review. Expert Rev Anticancer Ther. 2004 Apr;4(2):180-8. [Pubmed]
• External Links: Wikipedia; RxList; Drugs.com

Toronto Research Chemicals - B336750

Used as an antineoplastic. A selective retinoid X receptor (RXR) agonist.

REFERENCES

• Gniadecki R, Assaf C, Bagot M, Dummer R, Duvic M, Knobler R, Ranki A, Schwandt P, Whittaker S: The optimal use of bexarotene in cutaneous T-cell lymphoma. Br J Dermatol. 2007 Sep;157(3):433-40. Epub 2007 Jun 6. Pubmed
• Dragnev KH, Petty WJ, Shah SJ, Lewis LD, Black CC, Memoli V, Nugent WC, Hermann T, Negro-Vilar A, Rigas JR, Dmitrovsky E: A proof-of-principle clinical trial of bexarotene in patients with non-small cell lung cancer. Clin Cancer Res. 2007 Mar 15;13(6):1794-800. Pubmed
• Smit JW, Stokkel MP, Pereira AM, Romijn JA, Visser TJ: Bexarotene-induced hypothyroidism: bexarotene stimulates the peripheral metabolism of thyroid hormones. J Clin Endocrinol Metab. 2007 Jul;92(7):2496-9. Epub 2007 Apr 17. Pubmed
• Yen WC, Prudente RY, Corpuz MR, Negro-Vilar A, Lamph WW: A selective retinoid X receptor agonist bexarotene (LGD1069, targretin) inhibits angiogenesis and metastasis in solid tumours. Br J Cancer. 2006 Mar 13;94(5):654-60. Pubmed
• Lowe MN, Plosker GL: Bexarotene. Am J Clin Dermatol. 2000 Jul-Aug;1(4):245-50; discussion 251-2. Pubmed
• Farol LT, Hymes KB: Bexarotene: a clinical review. Expert Rev Anticancer Ther. 2004 Apr;4(2):180-8. Pubmed
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