Bazedoxifene

Manufactured by Pfizer

Sourced in United States

Bazedoxifene is a selective estrogen receptor modulator (SERM) used in laboratory research. It functions as a receptor agonist or antagonist depending on the specific tissue and estrogen receptor subtype.

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Lab products found in correlation

Palbociclib, by Pfizer (2 mentions) Raloxifene, by Merck Group (1 mentions) 17β estradiol 3 benzoate e2, by Merck Group (1 mentions) 17β estradiol, by Merck Group (1 mentions) 4 hydroxytamoxifen, by Merck Group (1 mentions) Ici 182 780, by Bio-Techne (1 mentions)

4 protocols using bazedoxifene

Palbociclib and Bazedoxifene in Breast Cancer

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The study was conducted in accordance with the International Conference on Harmonization Good Clinical Practice Standards and the Declaration of Helsinki. Institutional review board approval was obtained at Dana-Farber/Harvard Cancer Center (DF/HCC). The study was registered in ClinicalTrials.gov (NCT02448771). The DF/HCC Data and Safety Monitoring Committee, which is composed of clinical specialists with experience in oncology and who had no direct relationship with the study, reviewed and monitored toxicity and accrual data from the study. Participants provided written informed consent prior to the performance of any protocol specific procedures or assessments. The study was an investigator-initiated trial funded by Pfizer. Palbociclib and bazedoxifene were supplied by the manufacturer (Pfizer). The funder had no role in data collection, data analysis or data interpretation.

Tsuji J., Li T., Grinshpun A., Coorens T., Russo D., Anderson L., Rees R., Nardone A., Patterson C., Lennon N.J., Cibulskis C., Leshchiner I., Tayob N., Tolaney S.M., Tung N., McDonnell D.P., Krop I.E., Winer E.P., Stewart C., Getz G, & Jeselsohn R. (2022). Clinical Efficacy and Whole Exome Sequencing of Liquid Biopsies in a Phase IB/II study of Bazedoxifene and Palbociclib in Advanced Hormone Receptor-Positive Breast Cancer. Clinical cancer research : an official journal of the American Association for Cancer Research, 28(23), 5066-5078.

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Estradiol and SERM Effects on Bone Density

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Mice received subcutaneous injections of 17β-estradiol-3-benzoate (E2; 1 µg/mouse/day, Sigma–Aldrich, St Louis, MO, USA), raloxifene (ral; 60 µg/mouse/day, Sigma–Aldrich), lasofoxifene (las; 4 µg/mouse/day, Pfizer, Inc., NY, USA) or bazedoxifene (bza; 24 µg/mouse/day, Pfizer) dissolved in 100 µL miglyol oil (Vendico Chemical AB, Malmo, Sweden). Bza and las were kind gifts from Pfizer. Control mice received miglyol oil only (100 µL/mouse/day). Mice were treated for 16 consecutive days. It has previously been shown that mice treated with estradiol in doses similar to the one used here obtain serum estradiol levels corresponding to low diestrus levels (10–25 pg/mL) 20 (link). Body surface area calculations ensured that doses of ral, las, and bza used in mice were similar to those used in humans 21 (link). Indeed, Table1 shows that the doses of ral, las, and bza used result in a significant increase of total bone mineral density (BMD) in ovx mice.

Bernardi A.I., Andersson A., Grahnemo L., Nurkkala-Karlsson M., Ohlsson C., Carlsten H, & Islander U. (2014). Effects of lasofoxifene and bazedoxifene on B cell development and function. Immunity, Inflammation and Disease, 2(4), 214-225.

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NMU-Induced Mammary Carcinogenesis Protocol

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N-methyl-N-nitrosourea ISOPAC was purchased from Sigma Aldrich (St. Louis, MI). N-methyl-N-nitrosourea ISOPAC came in a bottle with 41.2% water and 8.5% acetic acid. On the day of injection, 98 ml sterile saline was added to the bottle to make 1% solution. The pH value of the solution was ~4 measured by a pH strip. The NMU solution bottle was wrapped with aluminum foil and kept on ice. Estradiol (E₂) was from Steraloids (Newport, RI). Conjugated equine estrogens (CEE) and bazedoxifene (BZA) were provided by Pfizer. CEE and BZA solutions were prepared in a vehicle of 2% Tween 80 and 0.5% methylcellulose according to the protocol of Peano et al.^{27 (link)} Anti-Ki67 and cleaved caspase-3 anti-bodies were purchased from Abcam (Cambridge, MA) and Cell Signaling Technology (Danvers, MA) respectively.

Yue W., Wang J., Atkins K.A., Bottalico L., Mesaros C., Blair I.A, & Santen R.J. (2018). Effect of a tissue selective estrogen complex on breast cancer: Role of unique properties of conjugated equine estrogen. International journal of cancer, 143(5), 1259-1268.

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Evaluating ESR1 Ligands and Inhibitors

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ESR1 ligands included 17β-estradiol (Sigma), ICI 182,780 (Tocris), and 4-hydroxytamoxifen (Sigma). Palbociclib, pipendoxifene and bazedoxifene were provided by Pfizer. (S)-3-(3-hydroxyphenyl)-4-methyl-2-(4-((S)-2-((R)-3-methylpyrrolidin-1-yl)propoxy)phenyl)-2H-chromen-6-ol (BPN1) and (E)-3-(4-((E)-2-(2-chloro-4-fluorophenyl)-1-(1H-indazol-5-yl)but-1-en-1-yl)phenyl)acrylic acid (BPL2) were synthesized as described (14 , 15 ). Ligands were dissolved in ethanol or DMSO.

Wardell S.E., Ellis M.J., Alley H.M., Eisele K., VanArsdale T., Dann S.G., Arndt K.T., Primeau T., Griffin E., Shao J., Crowder R., Lai J.P., Norris J.D., McDonnell D.P, & Li S. (2015). Efficacy of SERD/SERM Hybrid-CDK4/6 inhibitor combinations in models of endocrine therapy resistant breast cancer. Clinical cancer research : an official journal of the American Association for Cancer Research, 21(22), 5121-5130.

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