School Of Basic And Applied Sciences

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Subject: search.filters.subject.Drug development

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    FDA approved fused pyrimidine-based drugs
    (Elsevier, 2022-10-14T00:00:00) Thakur, Shikha; Ansari, Arshad J.; Joshi, Gaurav
    The present chapter is a compilation and analysis of USFDA approved small drug candidates about fused pyrimidine pharmacophore. Out of 63 drugs approved so far, nearly 38% of drugs are approved for chemotherapeutic treatment of cancer. Further, antiviral category shares 19% followed by drugs for cardiovascular disorders (14%), inflammatory diseases (9%), respiratory disorders (6%), neurological disorders (5%), benign prostatic hypertrophy (3%), erectile dysfunction (2%), diabetes (2%) and thrombocytopenia (2%). The chapter further focuses on key biological targets affected by the reported drug and their pharmacological mechanism of action. We have also focused on elucidating key chemical taxonomy utilized in fused pharmacophores of pyrimidine. The analysis suggested purine nucleosides (11 drugs) and xanthines/hypoxanthines (11 drugs) share the major chunk utilized in drug development out of fused pyrimidine nucleus. � 2023 Elsevier Ltd. All rights reserved.
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    Pore-forming proteins and their role in cancer and inflammation: Mechanistic insights and plausible druggable targets
    (Elsevier Ireland Ltd, 2022-08-30T00:00:00) Sankar, Jishnu; Arora, Sahil; Joshi, Gaurav; Kumar, Raj
    Perforin is a granular effector pore-forming protein formed in NK cells and Cytotoxic T lymphocytes. These cytotoxic proteins are part of the first-line immune defense in the human body. They ensure apoptosis of pathogen-infected cells or tumor cells in the human body. Activation of receptors on NK cell or T cell triggers secondary proteins in these cells. Further, it leads to Ca2+ dependent perforin egress towards the target cell, ensued by PI3K signaling pathway. Perforin undergoes oligomerization over the target cell membrane and forms transmembrane pores with the membrane-spanning domain-MACPF domain. Granzymes, proapoptotic serine proteases are released through these pores and initiate the target cell apoptotic pathway leading to the cell death. Although perforin is a savior for humans from tumor and viral infections, uncontrolled expression of the perforins leads to the autoimmune conditions, including Familial Hemophagocytic lymphohistiocytosis, insulin-dependent diabetes, and cerebral myocarditis. The present review is the concerted effort to highlight the mechanistic pathways concerning perforin secretion, NK cell and T cell-mediated cytotoxicity towards virus-infected and transformed cells. This is followed by the discussion on synthetic derivatives tested so far to inhibit the perforin in pre and clinical arena for certain unusual conditions. � 2022 Elsevier B.V.
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    The Concept of Receptor and Molecule Interaction in Drug Discovery and Development
    (Springer Singapore, 2021-02-18T00:00:00) Poduri, Ramarao; Jagadeesh, Gowraganahalli
    The mechanisms by which drugs act are different and unique to each class as they involve interactions with pharmacological receptors, enzymes, ion channels, and cellular transport processes. Hormones, neurotransmitters, and autocoids are natural chemical messengers that have a role in physiological and pathological regulatory processes. The interpretation of their action is determined by the localization and functional capacity of the specific receptor with which the �first messenger� interacts and the concentration of the chemical to which the receptor is exposed. This chapter focuses on physiological receptors where many of the drugs act in a manner similar to endogenous agonists or interfere with their interaction at the target to alleviate the symptoms of a disease. While doing so, many of these molecules have shown selectivity for receptor subtypes and signaling pathways. This is based on pharmacological scales such as affinity and intrinsic efficacy, and methods to quantify them are described within a theoretical concept. Based on these two drug properties, the overt action of a drug may be agonism or antagonism. Added to this gallery are allosteric modulators (positive or negative), partial agonists, inverse agonists, and biased agonists and antagonists. These are discussed with examples. Such new drug development is believed to improve the treatment of diseases with fewer adverse effects as a drug�s therapeutic and adverse effects are mediated by distinct pathways. In this chapter, we have extended the classical concept of the initiation of a pharmacological response with the binding of a drug to a receptor to the complexity of selectivity for receptor subtypes and signaling pathways. � Springer Nature Singapore Pte Ltd. 2021.