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Evolutionary Theories of Aging: A Systemic and Mechanistic Perspective
Published in Shamim I. Ahmad, Aging: Exploring a Complex Phenomenon, 2017
The study of this systemic organization of the living system, which has its equivalent inside any single cell, has been made possible by two main technological trends. First of all, there is the accumulation of various high-throughput data generated from different research areas such as proteomics, genomics, chemoproteomics, and phenomics which provides a better insight of the main components of the living cell [31–33]. Second, there is the progress made in computational and mathematical sciences [34]. These progresses, combined with the availability of increasingly powerful computational resources, allowed the development of software for retrospective analysis as well as the maintenance of web-based databases which are required for the gathering, classification, and efficient use of these experimental data.
Parasite and host kinases as targets for antimalarials
Published in Expert Opinion on Therapeutic Targets, 2023
Han Wee Ong, Jack Adderley, Andrew B. Tobin, David H. Drewry, Christian Doerig
Target identification is crucial toward realizing the benefits of target-based drug discovery. Two major target identification techniques have been used to identify antiplasmodial kinase targets. In vitro resistance generation with follow-up whole-genome sequencing is one such technique used frequently for identification of targets of kinase inhibitors. This has been successfully implemented for the imidazopyrazine KDU691 (PfPI4Kβ) [13], the 2-aminopyridine MMV390048 (PfPI4Kβ) [14], the 2-aminopyrazine UCT943 (PfPI4Kβ) [15], and 7-azaindole TCMDC-135051 (PfCLK3) [16]. Chemoproteomics is the other broad class of commonly-utilized target-identification technique, as reviewed in [17]. The main benefits of chemoproteomics are that it offers evidence of direct target engagement, and it may be utilized even when the target is refractory to resistance generation. One contributing factor to the popularity of chemoproteomics in kinase target identification is due to the availability of the established Kinobead technology, which uses a selection of promiscuous kinase inhibitors immobilized onto Sepharose beads to pull down kinases from cell lysates [18]. While originally designed for human kinase pulldowns, Kinobeads has been repurposed for pulldowns of kinases from Plasmodium lysate [14,18–22]. This technique has been implemented successfully in the identification of the kinase targets of the 2-aminopyridine MMV390048 (PfPI4Kβ) [14], pyridine-imidazole MMV030084 (PfPKG) [22], aminopyrimidine-thiazole compounds (PfPKG) [20,21], and purfalcamine (PfCDPK1) [23].
Proteomics for cancer drug design
Published in Expert Review of Proteomics, 2019
Amanda Haymond, Justin B. Davis, Virginia Espina
Chemoproteomics can be a powerful tool in drug discovery by providing a more complete picture of the potential protein interactions for any given therapeutic small molecule. This may reveal new mechanisms of action, and thereby, new targets for intervention. As many of the current therapeutic targets are enzymes such as kinases and proteases, activity based chemoproteomics provides a method for determining specificity for enzymes with similar catalytic domains or isoforms within the same enzyme family. The breadth of potential implications of chemoproteomics is highlighted by recent findings, such as the identification of a new therapeutic target for the treatment of lung cancer [55], the identification of a chemical class of inhibitors for an isoform of phospholipase A2 [56], the functional characterization of a member of the histone methyltransferase family [57], and the discovery of anti-proliferation effects resulting from off-targeting by a small molecule inhibitor not previously known to react with any proliferation related pathways [58].
Proteomics in the pharmaceutical and biotechnology industry: a look to the next decade
Published in Expert Review of Proteomics, 2021
Jennie R. Lill, William R. Mathews, Christopher M. Rose, Markus Schirle
Based on conversations with our industrial proteomics counterparts, we have reviewed the technological advances that we envision being most impactful in the bio-pharma proteomics arena in the next decade. Enhancements in sensitivity, integration of proteomics with other ‘omics’ technologies, expansion and higher utility of chemoproteomic technologies & advances in biomarker discovery in addition to software and data analysis solutions are all evolving and merging to provide more intricate and informative data to help fuel the drug discovery and development pipeline.