estramustine phosphate

Names

[ Name ]:
estramustine phosphate

[Synonym ]:
LS 299
[(8R,9S,13S,14S,17S)-13-methyl-17-phosphonooxy-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthren-3-yl] N,N-bis(2-chloroethyl)carbamate
ESTRAMUSTINE PHOSPHATE
Leo 299
Emcyt (free acid)
(17|A)-17-(phosphonooxy)estra-1,3,5(10)-trien-3-yl bis(2-chloroethyl)carbamate
Estradiol,3-(bis(2-chloroethyl)carbamate) dihydrogen phosphate

Biological Activity

[Description]:

Estramustine phosphate, an estradiol analog, is an orally active antimicrotubule chemotherapy agent. Estramustine phosphate depolymerises microtubules by binding to microtubule associated proteins (MAPs) and/or to tubulin. Estramustine phosphate can interfere mitosis, trigger cell death and induce apoptosis, which can be used for the research of cancer like prostate cancer[1][2][3].

[Related Catalog]:

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

Research Areas >> Endocrinology

Signaling Pathways >> Cell Cycle/DNA Damage >> Microtubule/Tubulin

Research Areas >> Inflammation/Immunology

Signaling Pathways >> Cytoskeleton >> Microtubule/Tubulin

[In Vitro]

Estramustine phosphate (1 µg/mL, 48 h) suppresses PC3 cell growth[1]. Estramustine phosphate (2 µg/mL, 48 h) elevates phosphatidylserine eversion amount on PC3 cells and induces PC3 cell apoptosis through reducing miR-31[1]. Estramustine phosphate (0-40 µM, 24-72 h) inhibits cell proliferation and tubulin cytoskeleton in RAW 264.7 cells[2]. Estramustine phosphate (10 µM, 24 h) inhibits TGF-β-induced RAW 264.7 cell migration, as well as TGF-β-induced uPA production by inhibiting Smad3 activation[2]. Cell Viability Assay[1] Cell Line: PC3 cells Concentration: 1 µg/ mL Incubation Time: 48 h Result: Suppressed PC3 cell growth. Immunofluorescence[2] Cell Line: RAW 264.7 cells Concentration: 10 µM Incubation Time: 24 h Result: Disrupted the interphase microtubules. Cell Migration Assay [2] Cell Line: 18 h of TGF-β treated RAW 264.7 cells Concentration: 10 µM Incubation Time: 24 h Result: Inhibited TGF-β-Induced Cell Migration.

[In Vivo]

Estramustine phosphate (Intraperitoneal injection, 4 or 12 mg/kg, a daily dose for 2 weeks) inhibits PAC120 tumor growth 53% by day 35[3]. Animal Model: Human prostate cancer xenograft PAC120[3] Dosage: 4 or 12 mg/kg, a daily dose for 2 weeks. Administration: Intraperitoneal injection Result: Inhibited PAC120 tumor growth 53% by day 35.

[References]

[1]. C Wei, et al. Estramustine phosphate induces prostate cancer cell line PC3 apoptosis by down-regulating miR-31 levels. Eur Rev Med Pharmacol Sci. 2018 Jan;22(1):40-45.

[2]. Sonja S Mojsilovic, et al. Estramustine Phosphate Inhibits TGF- β-Induced Mouse Macrophage Migration and Urokinase-Type Plasminogen Activator Production. Anal Cell Pathol (Amst). 2018 Sep 2;2018:3134102.

[3]. Stephane Oudard, et al. Activity of docetaxel with or without estramustine phosphate versus mitoxantrone in androgen dependent and independent human prostate cancer xenografts. J Urol. 2003 May;169(5):1729-34.

Chemical & Physical Properties

[ Density]:
1.4g/cm3

[ Boiling Point ]:
661.2ºC at 760mmHg

[ Molecular Formula ]:
C₂₃H₃₂Cl₂NO₆P

[ Molecular Weight ]:
520.38300

[ Flash Point ]:
353.7ºC

[ Exact Mass ]:
519.13400

[ PSA ]:
106.11000

[ LogP ]:
5.29900

[ Index of Refraction ]:
1.594

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: KG4300000

CHEMICAL NAME :: Estradiol, 3-(bis(2-chloroethyl)carbamate) dihydrogen phosphate

CAS REGISTRY NUMBER :: 4891-15-0

LAST UPDATED :: 199707

DATA ITEMS CITED :: 1

MOLECULAR FORMULA :: C23-H32-Cl2-N-O6-P

MOLECULAR WEIGHT :: 520.43

WISWESSER LINE NOTATION :: L E5 B666TTT&J E1 FOPQQO OOVN2G2G

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

MUTATION DATA

TYPE OF TEST :: Mutation in microorganisms

TEST SYSTEM :: Bacteria - Salmonella typhimurium

DOSE/DURATION :: 1000 ug/plate

REFERENCE :: URLRA5 Urological Research. (Springer Verlag New York, Inc., Service Center, 44 Hartz Way, Secaucus, NJ 07094) V.1- 1973- Volume(issue)/page/year: 7,119,1979