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Wednesday, 22 January 2014

New Drug Approvals 2013 - Pt. XXIII Bazedoxifene (DUAVEE™)


wikipedia: bazedoxifene             
ATC code: G03XC02

On 3 October 2013, FDA approved a new drug, bazedoxifene in combination with estrogen (trade name DUAVEE™), for treatment of moderate-to-sever vasomotor symptoms (hot flashes) associated with menopause and the prevention of postmenopausal osteoporosis in women. Bazedoxifene reduces the risk of excessive growth of the uterus (endothermetrial hyperplasia) that can be caused by estrogen.

Bazedoxifene (IUPAC name: 1-{4-[2-(Azepan-1-yl)ethoxy]benzy}-2-(4-hydroxyphenyl}-3-methyl-1H-indole-5-ol) is an indole based small molecule of molecular weight of 470.6 g/mol, polar surface area of 57.9, seven rotatable bonds, four hydrogen bond acceptors and one hydrogen bond donor. The compound is lipophilic with alogP 7.22, ApKa 10.12 and logD of 5.17. The compound is also known as WAY-140424, Bazedoxifene Acetate, Bazedoxifene, SID144206564, or SID124893775.

Canonical Smiles: Cc1c(c2ccc(O)cc2)n(Cc3ccc(OCCN4CCCCCC4)cc3)c5ccc(O)cc15
Standard InchI: InChI=1S/C30H34N2O3/c1-22-28-20-26(34)12-15-29(28)32(30(22)24-8-10-25(33)11-9-24)21-23-6-13-27(14-7-23)35-19-18-31-16-4-2-3-5-17-31/h6-15,20,33-34H,2-5,16-19,21H2,1H3

Bazedoxifene is a selective estrogen receptor  modulator (SERM) with a unique tissue and selectivity profile. Estrogen receptor (PDBe: 4iwf), is a transcription factor, which upon activation by a ligand, binds to DNA and regulates gene expression by mediating post-translational modification of histones and the associated transcriptional proteins.

Bazedoxifene is also known to prevent bone loss and osteoporotic fractures in postmenopausal women.  The drug, comes in the form of a tablet containing 0.45 mg estrogens and 20 mg bazedoxifene 20 mg. It is taken orally, once a day. Amongst other precautions, women taking DUAVEE should not take progestins, additional estrogens or additional estrogen agonist/antagonists. A detailed account of the prescribing information can be found here.

The license holders are Wyeth Pharmaceuticals, Inc. (a subsidiary of Pfizer Inc.,) based in Philadelphia, Pa.

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