Bazedoxifene free base | TSE-424 | CAS#198481-32-2

MedKoo Cat#: 120203 | Name: Bazedoxifene free base

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Description:

WARNING: This product is for research use only, not for human or veterinary use.

Bazedoxifene is a third generation selective estrogen receptor modulator (SERM), developed by Pfizer following the completion of their takeover of Wyeth Pharmaceuticals. In late 2013, Pfizer received approval for bazedoxifene as part of the combination drug DUAVEE in the prevention (not treatment) of postmenopausal osteoporosis. Bazedoxifene is an indole-based ER ligand that binds to both ERα (IC50 = 26 nM) and ERβ (IC50 = 99 nM).

Chemical Structure

Bazedoxifene free base

CAS#198481-32-2 (free base)

Theoretical Analysis

MedKoo Cat#: 120203

Name: Bazedoxifene free base

CAS#: 198481-32-2 (free base)

Chemical Formula: C30H34N2O3

Exact Mass: 470.2569

Molecular Weight: 470.60

Elemental Analysis: C, 76.57; H, 7.28; N, 5.95; O, 10.20

Price and Availability

Size	Price	Availability	Quantity
5mg	USD 300.00	2 Weeks
10mg	USD 550.00	2 Weeks

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Related CAS #

198481-32-2 (free base) 198480-56-7 (HCl) 198481-33-3 (acetate)

Synonym

Bazedoxifene free base, WAY-140424; WAY140424; WAY 140424; TSE 424; TSE424; TSE-424; Viviant.

IUPAC/Chemical Name

1-(4-(2-(azepan-1-yl)ethoxy)benzyl)-2-(4-hydroxyphenyl)-3-methyl-1H-indol-5-ol

InChi Key

UCJGJABZCDBEDK-UHFFFAOYSA-N

InChi Code

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

SMILES Code

OC1=CC2=C(N(CC3=CC=C(OCCN4CCCCCC4)C=C3)C(C5=CC=C(O)C=C5)=C2C)C=C1

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO, not in water

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

As of December 2011, the FDA have not given approval for the use of bazedoxifene in the US. The drug was approved in the European Union by the European Medicines Agency on April 27, 2009. On October 3, 2013 the FDA approved the combination product of bazedoxifene 20 mg with 0.45 mg Premarin (conjugated estrogens) for the treatment of menopausal osteoporosis and the treatment of moderate to severe hot flushes. This is the first approved hormone replacement therapy product that contains a SERM (bazedoxifene) and an estrogen.

Product Data

Product Data

Instruction

View handling instruction

Biological target:

Bazedoxifene (TSE-424) is a selective estrogen receptor modulator (SERM) with IC50s of 23 nM and 99 nM for ERα and ERβ, respectively.

In vitro activity:

The purpose of this study was to investigate the effects of Bazedoxifene on the functional changes of vascular smooth muscle cells (VSMCs) after PDGF-BB stimulation. PDGF-BB treatment significantly enhanced the viability and proliferation of VSMCs as indicated by CCK-8 and EdU assays (P < 0.01), while Bazedoxifene pretreatment could reduce the increased viability and proliferation of VSMCs caused by PDGF-BB (P < 0.05). Wound healing test also showed Bazedoxifene significantly attenuated the migration in the PDGF-BB stimulated VSMCs (P < 0.01). PDGF-BB also induced the phenotypic switch and decreased the autophagy level in VSMCs, manifested as a reduction in vimentin, SMA, and LC3 II (P < 0.01). These effects of PDGF-BB were partially reversed by Bazedoxifene (P < 0.05). These results indicated that Bazedoxifene may inhibit the proliferation and migration of VSMCs through up-regulate the autophagy level after PDGF-BB stimulation. Reference: Life Sci. 2020 Oct 15;259:118397. https://www.sciencedirect.com/science/article/abs/pii/S0024320520311504?via%3Dihub

In vivo activity:

The effect of Bazedoxifene in the progression of atherosclerosis was evaluated in apolipoprotein E-deficient (ApoE-/-) mice. Five-week-old male ApoE-/- mice were fed with High-fat diet (HFD) containing 5 mg/kg Bazedoxifene or a matching control for 12 weeks. Oil red O (ORO) staining was used to detect plaque size; immunohistochemical staining was used to detect the presence of endothelial cells, vascular muscle cells and phosphorylated STAT3 (P-STAT3) in localized plaques. The potential underlying mechanisms in human umbilical vein endothelial cells (HUVECs) and vascular muscle cells (VSMCs) was detected by Western blot analysis, Wound healing assay and Elisa assay. In the ApoE-/- mice fed with HFD, daily Bazedoxifene administration effectively attenuated atherosclerotic plaque area (P < 0.01), down-regulated IL-6 levels (P < 0.01), decreased STAT3 phosphorylation, reduced VSMCs proliferation and increased endothelial coverage in aortic vessels. Bazedoxifene did not inhibit the growth of HUVECs while suppressing the proliferation of VSMCs. Reference: Eur J Pharmacol. 2021 Feb 15;893:173822. https://www.sciencedirect.com/science/article/abs/pii/S0014299920309274?via%3Dihub

	Solvent	mg/mL	mM
Solubility
	DMSO	90.0	191.25

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 470.60 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Song W, Gao K, Huang P, Tang Z, Nie F, Jia S, Guo R. Bazedoxifene inhibits PDGF-BB induced VSMC phenotypic switch via regulating the autophagy level. Life Sci. 2020 Oct 15;259:118397. doi: 10.1016/j.lfs.2020.118397. Epub 2020 Sep 5. PMID: 32896557. 2. Luo P, Wang Y, Zhao C, Guo J, Shi W, Ma H, Liu T, Yan D, Huo S, Wang M, Li C, Lin J, Li S, Lv J, Zhang C, Lin L. Bazedoxifene exhibits anti-inflammation and anti-atherosclerotic effects via inhibition of IL-6/IL-6R/STAT3 signaling. Eur J Pharmacol. 2021 Feb 15;893:173822. doi: 10.1016/j.ejphar.2020.173822. Epub 2020 Dec 23. PMID: 33347820.

In vitro protocol:

In vivo protocol:

1. Luo P, Wang Y, Zhao C, Guo J, Shi W, Ma H, Liu T, Yan D, Huo S, Wang M, Li C, Lin J, Li S, Lv J, Zhang C, Lin L. Bazedoxifene exhibits anti-inflammation and anti-atherosclerotic effects via inhibition of IL-6/IL-6R/STAT3 signaling. Eur J Pharmacol. 2021 Feb 15;893:173822. doi: 10.1016/j.ejphar.2020.173822. Epub 2020 Dec 23. PMID: 33347820.

1: Rzemieniec J, Litwa E, Wnuk A, Lason W, Kajta M. Bazedoxifene and raloxifene protect neocortical neurons undergoing hypoxia via targeting ERα and PPAR-γ. Mol Cell Endocrinol. 2017 Aug 30. pii: S0303-7207(17)30450-1. doi: 10.1016/j.mce.2017.08.014. [Epub ahead of print] PubMed PMID: 28859903. 2: Bueno JAH, Arias L, Yu CR, Williams R, Komm BS. Efficacy and safety of bazedoxifene in postmenopausal Latino women with osteoporosis. Menopause. 2017 Sep;24(9):1033-1039. doi: 10.1097/GME.0000000000000889. PubMed PMID: 28837504. 3: Conjugated oestrogens/bazedoxifene. Aust Prescr. 2017 Jun;40(3):114-115. doi: 10.18773/austprescr.2017.039. Epub 2017 May 10. Review. PubMed PMID: 28798519; PubMed Central PMCID: PMC5478405. 4: McKeand W. Pharmacokinetics, Dose Proportionality, and Bioavailability of Bazedoxifene in Healthy Postmenopausal Women. Clin Ther. 2017 Sep;39(9):1769-1779. doi: 10.1016/j.clinthera.2017.07.012. Epub 2017 Jul 26. PubMed PMID: 28756067. 5: Xiao H, Bid HK, Chen X, Wu X, Wei J, Bian Y, Zhao C, Li H, Li C, Lin J. Repositioning Bazedoxifene as a novel IL-6/GP130 signaling antagonist for human rhabdomyosarcoma therapy. PLoS One. 2017 Jul 3;12(7):e0180297. doi: 10.1371/journal.pone.0180297. eCollection 2017. PubMed PMID: 28672024; PubMed Central PMCID: PMC5495564. 6: Pinkerton JV, Bushmakin AG, Bobula J, Lavenberg J, Komm BS, Abraham L. Hot flush frequency and severity at baseline as predictors of time to transient and stable treatment success: pooled analysis of two CE/BZA studies. Menopause. 2017 Jun 26. doi: 10.1097/GME.0000000000000918. [Epub ahead of print] PubMed PMID: 28654628. 7: Leignadier J, Dalenc F, Poirot M, Silvente-Poirot S. Improving the efficacy of hormone therapy in breast cancer: The role of cholesterol metabolism in SERM-mediated autophagy, cell differentiation and death. Biochem Pharmacol. 2017 Jun 19. pii: S0006-2952(17)30444-6. doi: 10.1016/j.bcp.2017.06.120. [Epub ahead of print] Review. PubMed PMID: 28642035. 8: Pinkerton JV, Bushmakin AG, Bobula J, Lavenberg J, Komm BS, Abraham L. Time to first occurrence of breast pain and vaginal bleeding in phase 3 trials of CE/BZA. Menopause. 2017 Jun 12. doi: 10.1097/GME.0000000000000935. [Epub ahead of print] PubMed PMID: 28609389. 9: Nordqvist J, Bernardi A, Islander U, Carlsten H. Effects of a tissue-selective estrogen complex on B lymphopoiesis and B cell function. Immunobiology. 2017 Aug;222(8-9):918-923. doi: 10.1016/j.imbio.2017.05.013. Epub 2017 May 16. PubMed PMID: 28551078. 10: Pinkerton JV, Bushmakin AG, Komm BS, Abraham L. Relationship between changes in vulvar-vaginal atrophy and changes in sexual functioning. Maturitas. 2017 Jun;100:57-63. doi: 10.1016/j.maturitas.2017.03.315. Epub 2017 Mar 22. PubMed PMID: 28539177. 11: Jover-Mengual T, Castelló-Ruiz M, Burguete MC, Jorques M, López-Morales MA, Aliena-Valero A, Jurado-Rodríguez A, Pérez S, Centeno JM, Miranda FJ, Alborch E, Torregrosa G, Salom JB. Molecular mechanisms mediating the neuroprotective role of the selective estrogen receptor modulator, bazedoxifene, in acute ischemic stroke: A comparative study with 17β-estradiol. J Steroid Biochem Mol Biol. 2017 Jul;171:296-304. doi: 10.1016/j.jsbmb.2017.05.001. Epub 2017 May 4. PubMed PMID: 28479229. 12: Pinkerton JV, Bushmakin AG, Abraham L, Komm BS, Bobula J. Time to transient and stable reductions in hot flush frequency in postmenopausal women using conjugated estrogens/bazedoxifene. Menopause. 2017 Sep;24(9):1011-1016. doi: 10.1097/GME.0000000000000888. PubMed PMID: 28463874. 13: Saito M, Marumo K. [Calcium and bone metabolism across women's life stages. Bone quality and treatment of osteoporosis by SERM.]. Clin Calcium. 2017;27(5):723-732. doi: CliCa1705723732. Japanese. PubMed PMID: 28439061. 14: Bazedoxifene for HRT? Drug Ther Bull. 2017 Apr;55(4):42-44. doi: 10.1136/dtb.2017.4.0466. Review. PubMed PMID: 28408389. 15: Xu B, Lovre D, Mauvais-Jarvis F. The effect of selective estrogen receptor modulators on type 2 diabetes onset in women: Basic and clinical insights. J Diabetes Complications. 2017 Apr;31(4):773-779. doi: 10.1016/j.jdiacomp.2016.12.010. Epub 2017 Jan 20. Review. PubMed PMID: 28185712; PubMed Central PMCID: PMC5350049. 16: Parish SJ, Gillespie JA. The evolving role of oral hormonal therapies and review of conjugated estrogens/bazedoxifene for the management of menopausal symptoms. Postgrad Med. 2017 Apr;129(3):340-351. doi: 10.1080/00325481.2017.1281083. Epub 2017 Jan 30. Review. PubMed PMID: 28132583. 17: Franks LN, Ford BM, Prather PL. Selective Estrogen Receptor Modulators: Cannabinoid Receptor Inverse Agonists with Differential CB1 and CB2 Selectivity. Front Pharmacol. 2016 Dec 22;7:503. doi: 10.3389/fphar.2016.00503. eCollection 2016. PubMed PMID: 28066250; PubMed Central PMCID: PMC5177629. 18: Sato Y, Tando T, Morita M, Miyamoto K, Kobayashi T, Watanabe R, Oike T, Matsumoto M, Nakamura M, Miyamoto T. Selective estrogen receptor modulators and the vitamin D analogue eldecalcitol block bone loss in male osteoporosis. Biochem Biophys Res Commun. 2017 Jan 22;482(4):1430-1436. doi: 10.1016/j.bbrc.2016.12.053. Epub 2016 Dec 11. PubMed PMID: 27974229. 19: Palacios S, Coronado PJ. New options for menopausal symptoms after 15 years of WHI Study. Minerva Ginecol. 2017 Apr;69(2):160-170. doi: 10.23736/S0026-4784.16.04007-7. Epub 2016 Dec 14. Review. PubMed PMID: 27973466. 20: Hill DA, Crider M, Hill SR. Hormone Therapy and Other Treatments for Symptoms of Menopause. Am Fam Physician. 2016 Dec 1;94(11):884-889. Review. PubMed PMID: 27929271.