Duavee: a tissue-selective estrogen complex for menopausal symptoms and prevention of osteoporosis

Tikoo, Deepika; Gupta, Mohit

doi:10.5455/2319-2003.ijbcp20150425

Cited by 5 publications

(2 citation statements)

References 9 publications

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“…We chose BZA because it has been extensively studied in clinical trials and is well tolerated. BZA was approved a number of years ago for the use in combination with conjugated equine estrogens for hormone replacement therapy in postmenopausal women (DUAVEE, Pfizer) in the US and for the prevention of osteoporosis as a single agent in Europe (Wardell et al, 2013a; Tikoo and Gupta, 2015). Importantly, it displayed strong antagonist and SERD profiles in the breast while retaining beneficial agonist properties in the bone and did not stimulate endometrial tissue in pre-clinical studies (Wardell et al, 2013a; Komm et al, 2005; Lewis-Wambi et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

The SERM/SERD bazedoxifene disrupts ESR1 helix 12 to overcome acquired hormone resistance in breast cancer cells

Fanning

Jeselsohn

Dharmarajan

et al. 2018

eLife

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Acquired resistance to endocrine therapy remains a significant clinical burden for breast cancer patients. Somatic mutations in the ESR1 (estrogen receptor alpha (ERα)) gene ligand-binding domain (LBD) represent a recognized mechanism of acquired resistance. Antiestrogens with improved efficacy versus tamoxifen might overcome the resistant phenotype in ER +breast cancers. Bazedoxifene (BZA) is a potent antiestrogen that is clinically approved for use in hormone replacement therapies. We found that BZA possesses improved inhibitory potency against the Y537S and D538G ERα mutants compared to tamoxifen and has additional inhibitory activity in combination with the CDK4/6 inhibitor palbociclib. In addition, comprehensive biophysical and structural biology studies show BZA’s selective estrogen receptor degrading (SERD) properties that override the stabilizing effects of the Y537S and D538G ERα mutations.

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Section: Introductionmentioning

confidence: 99%

The SERM/SERD bazedoxifene disrupts ESR1 helix 12 to overcome acquired hormone resistance in breast cancer cells

Fanning

Jeselsohn

Dharmarajan

et al. 2018

eLife

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“…Bazedoxifene (BZA) is another SERM/SERD hybrid with strong antagonist and SERD profiles in breast tissue and concomitant agonist properties in the bone, but without agonist properties in the endometrium [62,[94][95][96]. With long-term safety data in thousands of patients, BZA is already approved in the US as a hormone replacement therapy and is approved in Europe for the prevention of osteoporosis [62,94,[96][97][98][99]. In breast cancer, BZA demonstrated good oral bioavailability and improved PK profile compared to fulvestrant, as well as potent anti-tumor activity in both AI and SERM-resistant tumors and in ESR1-mutated cells [94,97,98,100].…”

Section: Innovation In Er Inhibition: Next Steps Beyond Serdsmentioning

confidence: 99%