Ki Hwan Kim

Publications (2)7.95 Total impact

• Article: Use of the nitrile oxide cycloaddition (NOC) reaction for molecular probe generation: a new class of enzyme selective histone deacetylase inhibitors (HDACIs) showing picomolar activity at HDAC6.

  Alan P Kozikowski, Subhasish Tapadar, Doris N Luchini, Ki Hwan Kim, Daniel D Billadeau
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  ABSTRACT: A series of hydroxamate based HDAC inhibitors containing a phenylisoxazole as the CAP group has been synthesized using nitrile oxide cycloaddition chemistry. An HDAC6 selective inhibitor having a potency of approximately 2 picomolar was identified. Some of the compounds were examined for their ability to block pancreatic cancer cell growth and found to be about 10-fold more potent than SAHA. This research provides valuable, new molecular probes for use in exploring HDAC biology.
  Journal of Medicinal Chemistry 08/2008; 51(15):4370-3. · 4.80 Impact Factor
• Article: Chemistry, biology, and QSAR studies of substituted biaryl hydroxamates and mercaptoacetamides as HDAC inhibitors-nanomolar-potency inhibitors of pancreatic cancer cell growth.

  Alan P Kozikowski, Yufeng Chen, Arsen M Gaysin, Doris N Savoy, Daniel D Billadeau, Ki Hwan Kim
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  ABSTRACT: The histone deacetylases (HDACs) are able to regulate gene expression, and inhibitors of the HDACs (HDACIs) hold promise in the treatment of cancer as well as a variety of neurodegenerative diseases. To investigate the potential for isoform selectivity in the inhibition of HDACs, we prepared a small series of 2,4'-diaminobiphenyl ligands functionalized at the para-amino group with an appendage containing either a hydroxamate or a mercaptoacetamide group and coupled to an amino acid residue at the ortho-amino group. A smaller series of substituted phenylthiazoles was also explored. Some of these newly synthesized ligands show low-nanomolar potency in HDAC inhibition assays and display micromolar to low-nanomolar IC(50) values in tests against five pancreatic cancer cell lines. The isoform selectivity of these ligands for class I HDACs (HDAC1-3 and 8) and class IIb HDACs (HDAC6 and 10) together with QSAR studies of their correlation with lipophilicity are presented. Of particular interest is the selectivity of the mercaptoacetamides for HDAC6.
  ChemMedChem 04/2008; 3(3):487-501. · 3.15 Impact Factor