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MedKoo Cat#: 529218 | Name: Endoxifen free base
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Description:

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

Endoxifen, also known as N-desmethyl-4-hydroxytamoxifen, is a chemical that is under development for estrogen receptor-positive breast cancer. It is also being evaluated as an antipsychotic for treatment of mania and other psychotic disorders. Endoxifen is a nonsteroidal selective estrogen receptor modulator (SERM) of the triphenylethylene group. It is an active metabolite of tamoxifen and has been found to be effective in patients that have failed previous hormonal therapies (tamoxifen, aromatase inhibitors, and fulvestrant). The prodrug tamoxifen is metabolized by the CYP2D6 enzyme to produce afimoxifene (4-hydroxytamoxifen) and endoxifen.

Chemical Structure

Endoxifen free base
Endoxifen free base
CAS#112093-28-4 (free base)

Theoretical Analysis

MedKoo Cat#: 529218

Name: Endoxifen free base

CAS#: 112093-28-4 (free base)

Chemical Formula: C25H27NO2

Exact Mass: 373.2042

Molecular Weight: 373.49

Elemental Analysis: C, 80.40; H, 7.29; N, 3.75; O, 8.57

Price and Availability

Size Price Availability Quantity
5mg USD 365.00 2 Weeks
10mg USD 650.00 2 Weeks
25mg USD 1,350.00 2 Weeks
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Related CAS #
1032008-74-4 (HCl) 112093-28-4 (free base) 1372937-28-4 (citrate) 1032008-66-4 (acetate) 1032008-71-1 (mesylate) 1197194-61-8 (E-isomer HCl)
Synonym
Endoxifen, (Z)-Endoxifen; 4-Hydroxy-N-desmethyltamoxifen; N-Desmethyl-4-hydroxytamoxifen;
IUPAC/Chemical Name
(Z)-4-(1-(4-(2-(methylamino)ethoxy)phenyl)-2-phenylbut-1-en-1-yl)phenol
InChi Key
MHJBZVSGOZTKRH-IZHYLOQSSA-N
InChi Code
InChI=1S/C25H27NO2/c1-3-24(19-7-5-4-6-8-19)25(20-9-13-22(27)14-10-20)21-11-15-23(16-12-21)28-18-17-26-2/h4-16,26-27H,3,17-18H2,1-2H3/b25-24-
SMILES Code
OC1=CC=C(/C(C2=CC=C(OCCNC)C=C2)=C(C3=CC=CC=C3)\CC)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
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
Product Data
Product Data
Instruction
View handling instruction
Biological target:
Endoxifen Z-isomer is the most important Tamoxifen metabolite responsible for eliciting the anti-estrogenic effects of this drug in breast cancer cells expressing estrogen receptor-alpha (ERα).
In vitro activity:
Treatment with endoxifen at 10 μM for 48 h resulted in significant cell death across all melanoma cell lines tested (Fig. 1). Treatment of B16F10 mouse melanoma and SK-MEL-5 human melanoma cell lines with endoxifen respectively resulted in 93.6 and 92.5% cell death. Reference: Cell Mol Biol Lett. 2018; 23: 3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5751858/
In vivo activity:
In an effort to develop a letrozole-resistant tumor model, this study extended treatment in the letrozole arm and letrozole resistance emerged in a subset (9 out of 17 mice that survived prolonged treatment) beginning at 25 weeks (Additional file 2a). At 27 weeks, letrozole treatment was discontinued and the subset harboring letrozole-resistant tumors (MCF7LR) (n = 9) were randomized to either Z-endoxifen (oral, 50 mg/kg) (n = 5) or tamoxifen (subcutaneous, 500 μg/day) (n = 4) for 4 weeks. Owing to weight loss issues previously observed with 75 mg/kg Z-endoxifen at 4 weeks, a reduced dose of 50 mg/kg Z-endoxifen was chosen for the extended experiment. In these MCF7LR tumors, 50 mg/kg Z-endoxifen significantly reduced tumor volume compared to tamoxifen (p = 0.045) (Additional file 2b). Reference: Breast Cancer Res. 2020; 22: 51. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7238733/
Solvent mg/mL mM
Solubility
DMSO 50.0 133.87
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 373.49 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.

Recalculate based on batch purity %
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. Chen P, Sheikh S, Ahmad A, Ali SM, Ahmad MU, Ahmad I. Orally administered endoxifen inhibits tumor growth in melanoma-bearing mice. Cell Mol Biol Lett. 2018 Jan 3;23:3. doi: 10.1186/s11658-017-0068-7. PMID: 29308069; PMCID: PMC5751858. 2. Thomas TJ, Thomas T, John S, Hsu HC, Yang P, Keinänen TA, Hyvönen MT. Tamoxifen metabolite endoxifen interferes with the polyamine pathway in breast cancer. Amino Acids. 2016 Oct;48(10):2293-302. doi: 10.1007/s00726-016-2300-6. Epub 2016 Jul 20. PMID: 27438264. 3. Jayaraman S, Hou X, Kuffel MJ, Suman VJ, Hoskin TL, Reinicke KE, Monroe DG, Kalari KR, Tang X, Zeldenrust MA, Cheng J, Bruinsma ES, Buhrow SA, McGovern RM, Safgren SL, Walden CA, Carter JM, Reid JM, Ingle JN, Ames MM, Hawse JR, Goetz MP. Antitumor activity of Z-endoxifen in aromatase inhibitor-sensitive and aromatase inhibitor-resistant estrogen receptor-positive breast cancer. Breast Cancer Res. 2020 May 19;22(1):51. doi: 10.1186/s13058-020-01286-7. PMID: 32430040; PMCID: PMC7238733. 4. Gingery A, Iwaniec UT, Subramaniam M, Turner RT, Pitel KS, McGovern RM, Reid JM, Marler RJ, Ingle JN, Goetz MP, Hawse JR. Skeletal and Uterotrophic Effects of Endoxifen in Female Rats. Endocrinology. 2017 Oct 1;158(10):3354-3368. doi: 10.1210/en.2016-1871. PMID: 28977607; PMCID: PMC5659691.
In vitro protocol:
1. Chen P, Sheikh S, Ahmad A, Ali SM, Ahmad MU, Ahmad I. Orally administered endoxifen inhibits tumor growth in melanoma-bearing mice. Cell Mol Biol Lett. 2018 Jan 3;23:3. doi: 10.1186/s11658-017-0068-7. PMID: 29308069; PMCID: PMC5751858. 2. Thomas TJ, Thomas T, John S, Hsu HC, Yang P, Keinänen TA, Hyvönen MT. Tamoxifen metabolite endoxifen interferes with the polyamine pathway in breast cancer. Amino Acids. 2016 Oct;48(10):2293-302. doi: 10.1007/s00726-016-2300-6. Epub 2016 Jul 20. PMID: 27438264.
In vivo protocol:
1. Jayaraman S, Hou X, Kuffel MJ, Suman VJ, Hoskin TL, Reinicke KE, Monroe DG, Kalari KR, Tang X, Zeldenrust MA, Cheng J, Bruinsma ES, Buhrow SA, McGovern RM, Safgren SL, Walden CA, Carter JM, Reid JM, Ingle JN, Ames MM, Hawse JR, Goetz MP. Antitumor activity of Z-endoxifen in aromatase inhibitor-sensitive and aromatase inhibitor-resistant estrogen receptor-positive breast cancer. Breast Cancer Res. 2020 May 19;22(1):51. doi: 10.1186/s13058-020-01286-7. PMID: 32430040; PMCID: PMC7238733. 2. Gingery A, Iwaniec UT, Subramaniam M, Turner RT, Pitel KS, McGovern RM, Reid JM, Marler RJ, Ingle JN, Goetz MP, Hawse JR. Skeletal and Uterotrophic Effects of Endoxifen in Female Rats. Endocrinology. 2017 Oct 1;158(10):3354-3368. doi: 10.1210/en.2016-1871. PMID: 28977607; PMCID: PMC5659691.
1. Chao TC, Pan WC, Tsai YF, Chou YC, Liu YR, Wang SF, Chen YJ, Souček P, Ueng YF. Plasma endoxifen and 4-hydroxytamoxifen levels in CYP2D6(C100T) carrying breast cancer patients and association with serum cholesterol. Toxicol Appl Pharmacol. 2019 Sep 1;378:114619. doi: 10.1016/j.taap.2019.114619. Epub 2019 Jun 10. Erratum in: Toxicol Appl Pharmacol. 2019 Oct 1;380:114701. PubMed [citation] PMID: 31195002 2. Lee CI, Fox P, Balakrishnar B, Balleine RL, Gao B, Provan P, Coulter S, Liddle C, Hui R, Wong M, Gurney H, Wilcken N. Tamoxifen-induced severe hot flashes and endoxifen levels: is dose reduction a safe and effective strategy? Breast. 2019 Aug;46:52-57. doi: 10.1016/j.breast.2019.05.009. Epub 2019 May 6. PubMed [citation] PMID: 31082762 3. Sanchez-Spitman AB, Swen JJ, Dezentje VO, Moes DJAR, Gelderblom H, Guchelaar HJ. Clinical pharmacokinetics and pharmacogenetics of tamoxifen and endoxifen. Expert Rev Clin Pharmacol. 2019 Jun;12(6):523-536. doi: 10.1080/17512433.2019.1610390. Epub 2019 Apr 30. Review. PubMed [citation] PMID: 31008668 4. Goetz MP. The development of endoxifen for breast cancer. Clin Adv Hematol Oncol. 2018 Feb;16(2):102-105. No abstract available. PubMed [citation] PMID: 29741509 5. Maximov PY, Abderrahman B, Fanning SW, Sengupta S, Fan P, Curpan RF, Rincon DMQ, Greenland JA, Rajan SS, Greene GL, Jordan VC. Endoxifen, 4-Hydroxytamoxifen and an Estrogenic Derivative Modulate Estrogen Receptor Complex Mediated Apoptosis in Breast Cancer. Mol Pharmacol. 2018 Aug;94(2):812-822. doi: 10.1124/mol.117.111385. Epub 2018 May 8. PubMed [citation] PMID: 29739819, PMCID: PMC6022805 6. Milroy LG, Koning B, Scheppingen DSV, Jager NGL, Beijnen JH, Koek J, Brunsveld L. A multi-gram-scale stereoselective synthesis of Z-endoxifen. Bioorg Med Chem Lett. 2018 May 1;28(8):1352-1356. doi: 10.1016/j.bmcl.2018.03.008. Epub 2018 Mar 13. PubMed [citation] PMID: 29548575 7. Chen P, Sheikh S, Ahmad A, Ali SM, Ahmad MU, Ahmad I. Orally administered endoxifen inhibits tumor growth in melanoma-bearing mice. Cell Mol Biol Lett. 2018 Jan 3;23:3. doi: 10.1186/s11658-017-0068-7. eCollection 2018. PubMed [citation] PMID: 29308069, PMCID: PMC5751858 8. Gingery A, Iwaniec UT, Subramaniam M, Turner RT, Pitel KS, McGovern RM, Reid JM, Marler RJ, Ingle JN, Goetz MP, Hawse JR. Skeletal and Uterotrophic Effects of Endoxifen in Female Rats. Endocrinology. 2017 Oct 1;158(10):3354-3368. doi: 10.1210/en.2016-1871. PubMed [citation] PMID: 28977607, PMCID: PMC5659691 9. Schroth W, Winter S, Mürdter T, Schaeffeler E, Eccles D, Eccles B, Chowbay B, Khor CC, Tfayli A, Zgheib NK, Eichelbaum M, Schwab M, Brauch H. Improved Prediction of Endoxifen Metabolism by CYP2D6 Genotype in Breast Cancer Patients Treated with Tamoxifen. Front Pharmacol. 2017 Aug 24;8:582. doi: 10.3389/fphar.2017.00582. eCollection 2017. PubMed [citation] PMID: 28955222, PMCID: PMC5609540 10. Goetz MP, Suman VJ, Reid JM, Northfelt DW, Mahr MA, Ralya AT, Kuffel M, Buhrow SA, Safgren SL, McGovern RM, Black J, Dockter T, Haddad T, Erlichman C, Adjei AA, Visscher D, Chalmers ZR, Frampton G, Kipp BR, Liu MC, Hawse JR, Doroshow JH, et al. First-in-Human Phase I Study of the Tamoxifen Metabolite Z-Endoxifen in Women With Endocrine-Refractory Metastatic Breast Cancer. J Clin Oncol. 2017 Oct 20;35(30):3391-3400. doi: 10.1200/JCO.2017.73.3246. Epub 2017 Aug 30. PubMed [citation] PMID: 28854070, PMCID: PMC5648176 11. Jordan VC. Endoxifen: The End, or Are We at the Beginning? J Clin Oncol. 2017 Oct 20;35(30):3378-3379. doi: 10.1200/JCO.2017.74.9325. Epub 2017 Aug 30. No abstract available. PubMed [citation] PMID: 28854071 12. Yuan S, Sun Q, Chen Y, Liao J. A Pharmacokinetic-Pharmacodynamic Model of Tamoxifen and Endoxifen to Predict Their Distribution and Effects on Inhibition of Tumor Growth. Drug Metab Lett. 2017;11(2):93-101. doi: 10.2174/1872312811666170815160751. PubMed [citation] PMID: 28814243 13. Hwang GS, Bhat R, Crutchley RD, Trivedi MV. Impact of CYP2D6 polymorphisms on endoxifen concentrations and breast cancer outcomes. Pharmacogenomics J. 2018 Apr;18(2):201-208. doi: 10.1038/tpj.2017.36. Epub 2017 Aug 1. Review. PubMed [citation] PMID: 28762370 14. Klopp-Schulze L, Joerger M, Wicha SG, Ter Heine R, Csajka C, Parra-Guillen ZP, Kloft C. Exploiting Pharmacokinetic Models of Tamoxifen and Endoxifen to Identify Factors Causing Subtherapeutic Concentrations in Breast Cancer Patients. Clin Pharmacokinet. 2018 Feb;57(2):229-242. doi: 10.1007/s40262-017-0555-z. PubMed [citation] PMID: 28540639 15. Thomas TJ, Thomas T, John S, Hsu HC, Yang P, Keinänen TA, Hyvönen MT. Tamoxifen metabolite endoxifen interferes with the polyamine pathway in breast cancer. Amino Acids. 2016 Oct;48(10):2293-302. doi: 10.1007/s00726-016-2300-6. Epub 2016 Jul 20. PubMed [citation] PMID: 27438264 16. Ahmad A, Sheikh S, Shah T, Reddy MS, Prasad B, Verma KK, Chandrakant BB, Paithankar M, Kale P, Solanki RV, Patel R, Barkate H, Ahmad I. Endoxifen, a New Treatment Option for Mania: A Double-Blind, Active-Controlled Trial Demonstrates the Antimanic Efficacy of Endoxifen. Clin Transl Sci. 2016 Oct;9(5):252-259. doi: 10.1111/cts.12407. Epub 2016 Jun 27. Erratum in: Clin Transl Sci. 2017 Mar;10 (2):117. PubMed [citation] PMID: 27346789, PMCID: PMC5350997 17. Fox P, Balleine RL, Lee C, Gao B, Balakrishnar B, Menzies AM, Yeap SH, Ali SS, Gebski V, Provan P, Coulter S, Liddle C, Hui R, Kefford R, Lynch J, Wong M, Wilcken N, Gurney H. Dose Escalation of Tamoxifen in Patients with Low Endoxifen Level: Evidence for Therapeutic Drug Monitoring-The TADE Study. Clin Cancer Res. 2016 Jul 1;22(13):3164-71. doi: 10.1158/1078-0432.CCR-15-1470. Epub 2016 Feb 4. PubMed [citation] PMID: 26847054 18. Dezentjé VO, Opdam FL, Gelderblom H, Hartigh den J, Van der Straaten T, Vree R, Maartense E, Smorenburg CH, Putter H, Dieudonné AS, Neven P, Van de Velde CJ, Nortier JW, Guchelaar HJ. CYP2D6 genotype- and endoxifen-guided tamoxifen dose escalation increases endoxifen serum concentrations without increasing side effects. Breast Cancer Res Treat. 2015 Oct;153(3):583-90. doi: 10.1007/s10549-015-3562-5. Epub 2015 Sep 14. PubMed [citation] PMID: 26369533, PMCID: PMC4589558 19. Zhang C, Zhong Q, Zhang Q, Zheng S, Miele L, Wang G. Boronic prodrug of endoxifen as an effective hormone therapy for breast cancer. Breast Cancer Res Treat. 2015 Jul;152(2):283-91. doi: 10.1007/s10549-015-3461-9. Epub 2015 Jun 14. PubMed [citation] PMID: 26071758, PMCID: PMC4524496 20. Chae YJ, Lee KJ, Lee HJ, Sung KW, Choi JS, Lee EH, Hahn SJ. Endoxifen, the active metabolite of tamoxifen, inhibits cloned hERG potassium channels. Eur J Pharmacol. 2015 Apr 5;752:1-7. doi: 10.1016/j.ejphar.2015.01.048. Epub 2015 Feb 11. PubMed [citation] PMID: 25680947