Drug Discovery Therapeutics Research Articles

Recent Advances in Pyrimidine-Based Drugs.

Pyrimidines have become an increasingly important core structure in many drug molecules over the past 60 years. This article surveys recent areas in which pyrimidines have had a major impact in drug discovery therapeutics, including anti-infectives, anticancer, immunology, immuno-oncology, neurological disorders, chronic pain, and diabetes mellitus. The article presents the synthesis of the medicinal agents and highlights the role of the biological target with respect to the disease model. Additionally, the biological potency, ADME properties and pharmacokinetics/pharmacodynamics (if available) are discussed. This survey attempts to demonstrate the versatility of pyrimidine-based drugs, not only for their potency and affinity but also for the improved medicinal chemistry properties of pyrimidine as a bioisostere for phenyl and other aromatic π systems. It is hoped that this article will provide insight to researchers considering the pyrimidine scaffold as a chemotype in future drug candidates in order to counteract medical conditions previously deemed untreatable.

Abstract 3319: Human triple-negative breast cancer stem cells utilized for drug discovery therapeutics for triple-negative breast cancer patients

Abstract Breast cancer is the most common malignancy among women in developed countries, affecting more than a million women per year worldwide. Of these, triple negative breast carcinoma represents 10-17 %. Triple negative breast carcinomas, characterized by estrogen, progesterone and HER2 receptor negativity are very aggressive tumors with poor prognosis. Breast Cancer Stem derived from triple negative parental Breast Cancer tumors, are a subpopulation of cells within the parental breast cancer population within the individual which are positive for the following markers: CD133+CD44+CD24+ESA+SSEA-1+TRA-1-61+& TRA1-81+ and Oct ¾ these Breast Cancer Stem cells are highly tumorigenic and possess the stem cell-like properties of self-renewal and the ability to produce differentiated progeny. Breast Cancer Stem cells also demonstrate up regulation of SSEA3+, SSEA4+ upon differentiation into parental cancer phenotype. Individualized treatment (tailored therapy) based on molecular biology markers of tumor and patient is the trend in clinical practice these days. However, molecular targets and predictors for the treatment of triple negative breast carcinoma do not currently exist. With the identification and characterization of Breast Cancer Stem Cells from parental triple negative tumors, enables one to screen novel drug candidates for potential development of therapeutics for triple negative Breast Cancer Patients. In this study we have utilized Breast Cancer Stem Cells from triple negative Tumors to screen potential drug candidates. The Breast Cancer Stem Cell based assay system may provide novel therapeutic approaches into treatment of triple negative breast cancer patients, which are resistant to standard chemotherapy and radiation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3319.