Mitotane - CAS 53-19-0
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Not Intended for Therapeutic Use. For research use only.
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Mitotane, is an antineoplastic medication used in the treatment of adrenocortical carcinoma.
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1.Assessment and management of advanced adrenocortical carcinoma using a precision oncology care model.
Elfiky AA1, Krishnan Nair HK1. Discov Med. 2016 Jan;21(113):49-56.
Within the category of orphan diseases and rare malignancies, adrenocortical carcinoma (ACC) represents an aggressive entity with high mortality and morbidity. While localized tumors which are diagnosed early can be cured with surgical intervention, there are prognostic factors which predict for micrometastases and consequent recurrent and advanced disease. In such cases, cytotoxic chemotherapy and mitotane have been utilized with a very modest degree of benefit. The poor prognosis of recurrent and advanced ACC has underscored the interest in nuanced characterization of ACC cases using next-generation sequencing (NGS)-based genomic and other '-omic' profiling to guide the precision medicine approach and personalized use of targeted and novel therapies.
2.Rapid and Complete Remission of Metastatic Adrenocortical Carcinoma Persisting 10 Years After Treatment With Mitotane Monotherapy: Case Report and Review of the Literature.
Ghorayeb NE1, Rondeau G, Latour M, Cohade C, Olney H, Lacroix A, Perrotte P, Sabourin A, Mazzuco TL, Bourdeau I. Medicine (Baltimore). 2016 Mar;95(13):e3180. doi: 10.1097/MD.0000000000003180.
Mitotane has been used for more than 5 decades as therapy for adrenocortical carcinoma (ACC). However its mechanism of action and the extent of tumor response remain incompletely understood. To date no cases of rapid and complete remission of metastatic ACC with mitotane monotherapy has been reported.A 52-year-old French Canadian man presented with metastatic disease 2 years following a right adrenalectomy for stage III nonsecreting ACC.He was started on mitotane which was well tolerated despite rapid escalation of the dose. The patient course was exceptional as he responded to mitotane monotherapy after only few months of treatment. Initiation of chemotherapy was not needed and he remained disease-free with good quality of life on low maintenance dose of mitotane during the following 10 years. A germline heterozygous TP53 exon 4 polymorphism c.215C>G (p. Pro72Arg) was found. Immunohistochemical stainings for IGF-2 and cytoplasmic β-catenin were positive.
3.The adrenal specific toxicant mitotane directly interacts with lipid membranes and alters membrane properties depending on lipid composition.
Scheidt HA1, Haralampiev I2, Theisgen S1, Schirbel A3, Sbiera S4, Huster D1, Kroiss M4, Müller P5. Mol Cell Endocrinol. 2016 Mar 18. pii: S0303-7207(16)30070-3. doi: 10.1016/j.mce.2016.03.022. [Epub ahead of print]
Mitotane (o,p'.-DDD) is an orphan drug approved for the treatment of adrenocortical carcinoma. The mechanisms, which are responsible for this activity of the drug, are not completely understood. It can be hypothesized that an impact of mitotane is mediated by the interaction with cellular membranes. However, an interaction of mitotane with (lipid) membranes has not yet been investigated in detail. Here, we characterized the interaction of mitotane and its main metabolite o,p'-dichlorodiphenyldichloroacetic acid (o,p'-DDA) with lipid membranes by applying a variety of biophysical approaches of nuclear magnetic resonance, electron spin resonance, and fluorescence spectroscopy. We found that mitotane and o,p'-DDA bind to lipid membranes by inserting into the lipid-water interface of the bilayer. Mitotane but not o,p'-DDA directly causes a disturbance of bilayer structure leading to an increased permeability of the membrane for polar molecules.
4.Adrenocortical carcinoma: Retrospective analysis of the last 22 years.
Guelho D1, Paiva I2, Vieira A3, Carrilho F2. Endocrinol Nutr. 2016 Mar 8. pii: S1575-0922(16)00024-3. doi: 10.1016/j.endonu.2015.12.009. [Epub ahead of print]
BACKGROUND: Adrenocortical carcinoma (ACC) is a rare disease with a poor prognosis. The clinical experience acquired, even from a small number of cases, has improved understanding of this condition. The purpose of this study is to characterize patients with ACC followed up at a Portuguese reference center over the past 22 years.
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CAS 53-19-0 Mitotane

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