Phenotype and target-based chemical biology investigations in cancers

Abstract

Chemical biology has been attracting a lot of attention because of the key roles of chemical methods and techniques in helping to decipher and manipulate biological systems. Although chemical biology encompasses a broad field, this review will focus on chemical biology aimed at using exogenous chemical probes to interrogate, modify and manipulate biological processes, at the cellular and organismal levels, in a highly controlled and dynamic manner. In this area, many advances have been achieved for cancer biology and therapeutics, from target identification and validation based on active anticancer compounds (forward approaches) to discoveries of anticancer molecules based on some important targets including protein-protein interaction (reverse approaches). Herein we attempt to summarize some recent progresses mainly from China through applying chemical biology approaches to explore molecular mechanisms of carcinogenesis. Additionally, we also outline several new strategies for chemistry to probe cellular activities such as proximity-dependent labeling methods for identifying protein-protein interactions, genetically encoded sensors, and light activating or repressing gene expression system.

Into the Fray! A Beginner's Guide to Medicinal Chemistry

“…[3][4][5][6] However more recently, efforts to reconcile the advantages of each approach, either through dual assay approaches, sophisticated in silico assessment or phenotypic chemical biology, are becoming increasingly commonplace in modern drug discovery. [7][8][9][10][11] Furthermore, the expanded incorporation of structural biology methodology encompassing amongst others, X-ray crystallography, cryo-EM, NMR and mass spectrometry in early screening campaigns provides additional means for the identification and validation of biologically active compounds, as well as providing structural and kinetic information of compound-target interactions. [12] These additional orthogonal methods are particularly useful in reducing the impact of promiscuous compounds and false positives, which plague screening campaigns.…”

ANP32B-mediated repression of p53 contributes to maintenance of normal and CML stem cells

“…[1][2][3][4] Chronic myelogenous leukemia (CML) results from malignant transformation of HSCs by the BCR-ABL1 oncogene, which is generated by t(9;22) chromosome translocation. 5 Tyrosine kinase inhibitors (TKIs) are highly effective in inducing remission of patients with CML, but they fail to target LSCs of CML, and recurrence is commonly seen following discontinuation of TKI treatment. [5][6][7] Several self-renewal regulators have been investigated in both HSC and LSC contexts.…”

“…5 Tyrosine kinase inhibitors (TKIs) are highly effective in inducing remission of patients with CML, but they fail to target LSCs of CML, and recurrence is commonly seen following discontinuation of TKI treatment. [5][6][7] Several self-renewal regulators have been investigated in both HSC and LSC contexts. 8,9 The tumor suppressor p53, a well-known transcriptional regulator during the cellular stress response, is a critical regulator of HSCs behavior and essential to maintain HSCs quiescence through targeting Gfi-1 and Necdin [10][11][12] and acts as the mediator of enhanced apoptosis of LSCs.…”

Multifunctional polyethyleneimine for synthesis of core-shell nanostructures and electrochemiluminescent detection of three AMI biomarkers

“…This strategy involved the capture antibody (Ab)-coated magnetic beads and the luminophore-labeled detection Ab to form a sandwich-type complex with the target antigen (Ag), which is quite complicated and expensive. By contrast, in label-free-based methods [8][9][10][11], only one antibody was involved, which is simple but lack of sensitivity. Hence, nanomaterials were commonly selected to amplify ECL signals [2,12].…”