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Drug Discovery

Medicinal Chemistry

   Medicinal chemistry deals with the design, optimization, and development of chemical compounds for their use as drugs. It is a multidisciplinary field of science, which is comprised of the synthesis of potential drugs and the investigation of their interactions with corresponding biological targets in order to grasp the knowledge of those medicinal effects of drugs, its metabolism, and possible adverse effects. In particular, medicinal chemistry, in common practice, encompasses synthetic organic chemistry focusing on small organic molecules, aspects of natural products, and computational chemistry in close combination with chemical biology, enzymology, and structural biology.

 

   Our researches concentrate on the development of kinase inhibitors, which are front runners in signaling pathway because of their protein kinase inhibitory effect. Protein kinases comprise a major fraction of the signaling elements on whose activities the survival of cancer is dependent

 

   Our recent accomplishments include:

   Development of a Selective and Potent Inhibitor of RET Gatekeeper Mutants

  • Aberrant RET kinase signaling plays critical roles in several human cancers such as thyroid carcinoma.

  • The gatekeeper mutants (V804L or V804M) of RET are resistant to currently approved RET inhibitors such as cabozantinib and vandetanib.

  • In our lab, for the first time, we reported a highly selective and extremely potent RET inhibitor(6i).

   Discovery of a RET kinase inhibitor exhibiting enhanced metabolic stability

  • By hopping the scaffold of compound 6g, a novel and specific RET inhibitor was designed to enhance the metabolic stability.

  • Based on its exceptional kinase selectivity, great potency, and metabolic stability, 15l should be a key tool in studies aimed at understanding RET biology.

Pre-clinical Study

   Pre-clinical study is an investigation to test a drug, a procedure, or another medical treatment in animals. In drug development, pre-clinical development, also  known as pre-clinical studies and non-clinical studies, is a stage of research that is conducted in prior to clinical trials, and during which important feasibility, iterative testing and drug safety data is collected. In addition, it includes in vivo or in vitro experiments in which test articles are studied prospectively in test systems under laboratory conditions to determine their safety. We assume that in vitro assays predict in vivo effects, the effects of chemicals in laboratory animals which might affect humans, and make the researchers able to anticipate possible toxicity by using high doses in animals. These assumptions are broadly true; however, we are uncertain despite the assumptions whether a chemical will show toxic effects on human body or not.

   The objective of developing adequate data is to decide that the tested chemical is reasonably efficient and safe in animal models and can proceed with human trials of the drug. This means a laboratory test of a new drug is usually done on animal subjects to see if the treatment is truly safe to be tested on humans.

   Pharmacokinetics & Pharmacodynamics

  • Pharmacokinetics(PK) is what the body does to the drug. ADME is an abbreviation used in pharmacokinetics and pharmacology which stands for "absorption, distribution, metabolism, and excretion", and describes the disposition of a pharmaceutical compound within an organism.

  • Pharmacodynamics(PD) is what the drug does to the body. In PD, we evaluate possible effects of the drug by testing its toxicity and studying in vivo efficacy in a mouse model with related disease to determine a right dose based on PK data and compound solubility.

   New insight into the molecular mechanisms

  • The cellular phenotype and signaling cascades which are modulated by small molecules.

  • Apoptosis and autophagy pathways