Estramustine
目录号 : GC67333Estramustine 是一种抗肿瘤剂。Estramustine 通过与微管蛋白 1 (tubulin 1)结合来解聚微管,具有抗有丝分裂活性,对 DU 145 细胞有丝分裂的 IC50 大约为 16 μM。Estramustine 在前列腺肿瘤异种移植模型中阻断前列腺肿瘤细胞有丝分裂。
Cas No.:2998-57-4
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Estramustine is an antineoplastic agent. Estramustine depolymerizes microtnbules by binding to tubulin 1, exhibits antimitotic activity with an IC50 value of ~16 μM for mitosis of DU 145 cells. Estramustine blocks cells at mitosis in prostate tumor xenografts[1].
[1]. DahllÖf B, et al. Estramustine depolymerizes microtubules by binding to tubulin. Cancer Res. 1993 Oct 1;53(19):4573-81.
Cas No. | 2998-57-4 | SDF | Download SDF |
分子式 | C23H31Cl2NO3 | 分子量 | 440.4 |
溶解度 | 储存条件 | Store at -20°C | |
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Estramustine phosphate sodium
Drug Intell Clin Pharm 1984 May;18(5):368-74.PMID:6373212DOI:10.1177/106002808401800502.
Estramustine phosphate is approved by the Food and Drug Administration for oral use in the palliative treatment of patients with metastatic and/or progressive carcinoma of the prostate. Estramustine is a conjugate of 17 beta-estradiol and the carbamate of nitrogen mustard. Although its therapeutic efficacy has been demonstrated, it is not clear to what extent each constituent contributes to Estramustine's effectiveness. Estramustine phosphate therapy achieves objective response rates of 60-90 percent in advanced stage D prostatic cancer patients with no prior hormonal therapy. These results are consistent with those obtained with conventional hormonal therapy in similar patient populations. Therapeutic efficacy does not appear to increase when Estramustine is used concurrently with other cytotoxic chemotherapeutic agents. An objective response rate of 20-30 percent can be anticipated in patients refractory to conventional hormonal therapy. It is in this group, the estrogen-resistant patients, that Estramustine shows the most promise. Adverse effects of Estramustine are similar to those of diethylstilbestrol. Gastrointestinal and cardiovascular side effects appear to be the most important and may be severe enough to require discontinuation of therapy.
Estramustine resistance
Gen Pharmacol 1999 Aug;33(2):107-13.PMID:10461848DOI:10.1016/s0306-3623(98)00272-9.
Estramustine (EM), a conjugate of nornitrogen mustard and estradiol, is a antimicrotubule drug currently in use for the treatment of advanced prostatic carcinoma. Experimental data are accumulating concerning the antitumor effect of EM in other malignancies, and clinical studies in other malignancies are ongoing. This review summarizes the information available to date concerning the effects of EM and the development of drug resistance. EM depolymerizes microtubules by binding to microtubule-associated proteins (MAPs) as well as tubulin. Because of the radiosensitizing effect of this drug there has been a recent increase in interest concerning Estramustine and its clinical use. Recently, it was proposed that EM induces an apoptotic cell death in glioma cells in vitro and in a rat model. EM resistance is distinct from MDR phenotype; it has been used in combination with antimitotic agents which are part of the MDR phenotype. Observations made with estramustine-resistant cell lines show the acquisition of Estramustine resistance is a function of multiple adaptation by changes at tubulin expression pattern, and is also associated with changes in tau expression and phosphorylation.
Long responders to Estramustine monophosphate. Report of two cases and literature review
Arch Esp Urol 2019 Sep;72(7):712-715.PMID:31475684doi
Objective: Estramustine is an stable estradiol and nitrogenated mustard conjugatewith antymicotic properties. Currently, with the appearance of chemotherapy and new molecules, estramustin acetate is not a drug of choice for castration resistant prostate cancer. Methods: We describe two patients with castration resistant prostate cancer under treatment with Estramustine acetate and complete biochemical response and stable disease. We review the literature to elucidate if the drug should be stopped and changed for the new molecules that have demonstrated survival increase. Results: To our knowledge, there are not data in the literature to either solve the questions posed or shed light regarding cumulative toxicity due to prolongued use of Estramustine acetate. Conclusions: We recognize that these clinical cases do not translate that Estramustine acetate is a first line treatment for patients with CRPC. Nevertheless, they translate the heterogeneity of CRPC. It would be interesting to investigate the combination of new agents with Estramustine acetate as well as the search of biomarkers that enable selection of candidates who could respond to Estramustine acetate.
Estramustine phosphate sodium. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in prostate cancer
Drugs Aging 1995 Jul;7(1):49-74.PMID:7579781DOI:10.2165/00002512-199507010-00006.
Estramustine phosphate sodium (Estramustine phosphate), a unique antitumour agent, is selectively taken up by prostate cells and exerts antineoplastic effects by interfering with microtubule of dynamics and by reducing plasma levels of testosterone. In noncomparative studies of Estramustine phosphate in patients with hormone-refractory disease, objective response rates ranging from 19 to 69% have been reported. Preliminary clinical investigations indicate that combining Estramustine phosphate with vinblastine, etoposide or paclitaxel improves objective response rates over single-agent treatment, although no survival benefit over single-agent treatment has been demonstrated to date. In comparative studies, Estramustine phosphate produces similar objective response rates to conventional antineoplastic agents in patients with hormone-refractory prostate cancer. In previously untreated patients with advanced metastatic hormone-responsive prostate cancer, objective responses are achieved in approximately 80% of patients. Estramustine phosphate appears to be at least as effective as estrogen or flutamide therapy in these patients. Nausea and vomiting are the most frequently observed adverse effects of treatment with Estramustine phosphate. While these symptoms are usually mild to moderate in nature, they may occasionally be more troublesome to the patient and necessitate withdrawal of treatment. Cardiovascular complications are a more serious, though less frequently encountered, adverse effect of the drug. However, these complications may be avoided by careful patient selection and prophylactic treatment measures. Unlike some other antineoplastic agents, Estramustine phosphate is rarely associated with myelosuppression. In addition to producing similar objective response rates to other established agents, Estramustine phosphate improves the subjective status of many patients and has been shown to reduce the intensity of pain and improve the performance status of patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Estramustine-based chemotherapy
Semin Urol Oncol 1997 Feb;15(1):13-9.PMID:9050135doi
Long misclassified as an alkylating agent, Estramustine phosphate is a stable conjugate of estradiol and nornitrogen mustard with antimitotic properties. Binding of the drug to microtubule-associated proteins, tubulin, and proteins of the nuclear matrix are presently considered to be the most likely mechanisms underlying the cytotoxicity of Estramustine in androgen-independent prostatic carcinoma. Identification of these mechanisms of action has led to clinical reevaluation of Estramustine phosphate (EMP) in several rationally designed drug combinations. Combination of EMP with either vinblastine, paclitaxel or etoposide has produced antitumor responses in 30% to 60% of patients with metastatic hormone-refractory prostate carcinoma as determined by reduction in bidimensionally measurable soft tissue disease, pain, and serum prostate-specific antigen. Whereas the antitumor activity of the combinations has been greater than additive for the single agents, the toxicities of treatment have not been greater than predicted for the individual drugs. The promising results of EMP-based chemotherapy encourage additional laboratory and clinical investigations to develop more effective therapy for hormone-refractory disease and for selected patients with earlier stages of prostate cancer.