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Job Description
The successful candidate will work with Prof YAO Shao Qin on chemical biology/drug discovery-related research under a project on "Targeted covalent Inhibitors against key epigenetic proteins (NMRC)".
Human kinases and epigenetic proteins are important therapeutic targets. Recent development of selective and potent inhibitors of proteins has yielded remarkable results in disease treatment, with numerous drugs already on the market, and many more undergoing clinical trials. Notwithstanding, the discovery of new covalent kinase and epigenetic drugs remains highly challenging, including issues related to selectivity, efficacy and acquired drug resistance. Taking cue from the kinase drug discovery field, the hypothesis of these projects is that a universal strategy for targeted covalent inhibitors (TCIs) capable of potent target inhibition and minimal acquired drug resistance is possible, if highly effective small molecules could be developed to covalently target non-cysteine (C) nucleophilic residues within/near the active-site of kinase/epigenetic proteins. Our recent discovery of covalent kinase inhibitors against BCR-ABL (a key kinase for CML) in which CBA/SA and EBA warheads formed stable, (reversible and irreversible) covalent linkage with catalytic lysine (K) in Abl kinase under cellular environments indicates other covalent chemistries are feasible. Therefore, the goal of the current proposals is to confirm covalent chemistries targeting other nucleophilic residues (E/D/R/M/etc) are possible, and amenable to the development of cell-active, selective TCIs for various therapeutic proteins.
The scope of this proposal will be limited to the fundamental basic science, and NOT the actual clinical implementation, of the developed chemical/chemical biology tools. Therefore, only cell-based and basic animal models will be tested on newly developed, select small-molecule TCIs. Experience/skills required are organic synthesis/chemical biology/protein chemistry/proteomics/molecular biology/cell biology (only some of above skills are required)
Qualifications
- Qualifications / Discipline: PhD or equivalent in Chemistry/Biochemistry/Pharmaceutical Chemistry/Biology
- Skills: Organic synthesis/chemical biology/protein chemistry/proteomics/molecular biology/cell biology
- Experience: PhD holders with < 5 years of experience in any/some of above fields. Those with no experience may also apply
