葉燈光

TK Yeh 2葉燈光  副研究員
生技與藥物研究所
Email: tkyeh@nhri.edu.tw

 

EDUCATION

  • Ph.D. Pharmaceutics, The Ohio State University, USA.
  • M.S. Pharmaceutics and Pharmaceutical Chemistry, The Ohio State University, USA
  • B.S., Pharmacy, Taipei Medical University, Taiwan

PROFESSIONAL EXPERIENCES

  • Associate Investigator, Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Taiwan
  • Assistant Investigator, Division of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Taiwan
  • Research Associate, Division of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Taiwan
  • Research Scientist, Optimum Therapeutics, LLC, Columbus, Ohio, USA
  • Postdoctoral Research Associate, The Ohio State University, USA
  • Graduate Research Associate, The Ohio State University, USA
  • Research Investigator, China Chemical and Pharmaceutical Research Center

RESEARCH INTERESTS

Dr. Yeh’s research interests are in the areas of preclinical and clinical pharmacokinetics, drug metabolism, drug interaction, drug delivery and biopharmaceutics. The projects include determination of the physical and chemical properties of a therapeutic entity, method development and validation of sensitive and specific analytical techniques for the identification and quantitation of new chemical entities and/or drugs and their metabolites in biological matrices, characterizing the in vivo pharmacokinetics and metabolism of new chemical entities and/or drugs using animal models, scaling preclinical and in-vitro data to predict events in humans for preliminary assessment of safe exposure levels, determination of the metabolite profiles of drug candidates using hepatocytes and liver microsomes containing a single enzyme, identify Phase I or Phase II enzymes responsible for metabolite formation, predict drug interactions due to inhibition or induction of drug metabolizing enzymes, regulation and function of drug-metabolizing enzymes, particularly with an interest in elucidating mechanisms of drug-drug, herb-drug and food-drug interactions and studying the role of drugs and natural products in drug induced hepatotoxicity and in cancer chemotherapy, development of intravenous and extravascular dosage formulations for synthetic organic molecules to optimize their therapeutic values, and improving the drug delivery system of drugs through the use of novel formulations (i.e. micro-and nanoparticles) to help localize the drug to target sites and minimize drug toxicity.

RESEARCH ACTIVITIES & ACCOMPLISHMENTS

Dr. Yeh is currently involved in the early stage new small molecular entities discovery at Institute of Biotechnology and Pharmaceutical Research (IBPR). He has contributed to help IBPR drug discovery team to the success of several discovery projects leading to the selection and/or termination of development candidate(s) from the pharmacokinetics and drug metabolism aspects. A significant portion of his present and previous researches has been to develop novel assay methods and formulations to evaluate pharmacokinetic properties and drug metabolites of the small chemical entities and drugs, and to integrate the in vitro and in vivo correlation to extrapolate into human clinical trials.

SELECTED PUBLICATIONS

  1. Hesperetin promotes longevity and delays aging via activation of Cisd2 in naturally aged mice. Yeh CH, Shen ZQ, Wang TW, Kao CH, Teng YC, Yeh TK, Lu CK, Tsai TF. J Biomed Sci 2022. Jul 24: 29, 53.
  2. Synthesis and Evaluation of Small Molecule Drug Conjugates Harnessing Thioester-Linked Maytansinoids. Lo, CF;Chiu, TY;Liu, YT;Huang, LR;Yeh, TK;Huang, KH;Liu, KL;Hsu, CY;Fang, MY;Huang, YC;Hsu, TA;Chen, CT;Tsou, LK. Pharmaceutics. 2022 Jun 21;14(7):1316.
  3. Rejuvenating hepatic tumor microenvironment immunity with a phosphatidylserine-targeting small molecule drug conjugate. Huang KH, Liu YT, Pan PY, Lo CF, Liu KL, Yeh TK, Huang LR, Tsou LK. Biomed Pharmacother. 2022 May 11;151:113084
  4. Click Chemistry and Multicomponent Reaction for Linker Diversification of Zinc Dipicolylamine-Based Drug Conjugates. Tsai CH, Chiu TY, Chen CT, Hsu CY, Tsai YR, Yeh TK, Huang KH, Tsou LK. Front Chem. 2022 Feb 15;9:822587.
  5. Discovery of Potential Neuroprotective Agents against Paclitaxel-Induced Peripheral Neuropathy. Chen YF, Wu CH, Chen LH, Lee HW, Lee JC, Yeh TK, Chang JY, Chou MC, Wu HL, Lai YP, Song JS, Yeh KC, Chen CT, Lee CJ, Shia KS, Shen MR. J Med Chem. 2022 Mar 2. 65(5):4767-4782.
  6. Discovery and development of a novel N-(3-bromophenyl)-{[(phenylcarbamoyl) amino]methyl}-N-hydroxythiophene-2-carboximidamide indoleamine 2,3-dioxygenase inhibitor using knowledge-based drug design. Yeh TK†, Song JS†, Chang PW, Yu JC, Chang CH, Liao FY, Tien YW, Kuppusamy R, Li AS, Chen CH, Chen CW, Lin LM, Chang HH, Huang CH, Yao JY, Wu MH, Peng YH, Hsueh CC, Hsiao WC, Chen PH, Lin CY, Hsieh SH, Shih C, Hung MS, Wu SY, Kuo CC, Ueng SH. Eur J Med Chem. 2022, 229, 114043
  7. Discovery of BPR1R024, an Orally Active and Selective CSF1R Inhibitor that Exhibits Antitumor and Immunomodulatory Activity in a Murine Colon Tumor Model. Lee KH, Yen WC, Lin WH, Wang PC, Lai YL, Su YC, Chang CY, Wu CS, Huang YC, Yang CM, Chou LH, Yeh TK, Chen CT, Shih C, Hsieh HP.J Med Chem. 2021 Oct 14;64(19):14477-14497.
  8. Design and synthesis of novel orally selective and type II pan-TRK inhibitors to overcome mutations by property-driven optimization.. Li MC, Lin WH, Wang PC, Su YC, Chen PY, Fan CM, Chen CP, Huang CL, Chiu CH, Chang L, Chen CT, Yeh TK, Hsieh HP. Eur J Med Chem. 2021 Nov 15;224:113673.
  9. Discovery and Synthesis of a Pyrimidine-Based Aurora Kinase Inhibitor to Reduce Levels of MYC Oncoproteins. Chi YH†, Yeh TK†, Ke YY, Lin WH, Tsai CH, Wang WP, Chen YT, Su YC, Wang PC, Chen YF, Wu ZW, Yeh JY, Hung MC, Wu MH, Wang JY, Chen CP, Song JS, Shih C, Chen CT, Chang CP. J Med Chem. 2021 64(11):7312-7330.
  10. DBPR108, a novel dipeptidyl peptidase-4 inhibitor with antihyperglycemic activity. Yeh KC, Yeh TK*, Huang CY, Hu CB, Wang MH, Huang YW, Chou LH, Ho HH, Song JS, Hsu T, Jiaang WT, Chao YS, Chen CT*. Life Sci. 2021 May 5;278:119574.
  11. A highly selective and potent CXCR4 antagonist for hepatocellular carcinoma treatment. Song JS, Chang CC, Wu CH, Dinh TK, Jan JJ, Huang KW, Chou MC, Shiue TY, Yeh KC, Ke YY, Yeh TK, Ta YN, Lee CJ, Huang JK, Sung YC, Shia KS, Chen Y. Proc Natl Acad Sci U S A. 2021 Mar 30;118(13):e2015433118.
  12. Potent and orally active purine-based fetal hemoglobin inducers for treating β-thalassemia and sickle cell disease. Lai ZS, Yeh TK, Chou YC, Hsu T, Lu CT, Kung FC, Hsieh MY, Lin CH, Chen CT, James Shen CK, Jiaang WT. Eur J Med Chem. 2021 Jan 1;209:112938.
  13. BPRDP056, a novel small molecule drug conjugate specifically targeting phosphatidylserine for cancer therapy. Chen YY, Lo CF, Chiu TY, Hsu CY, Yeh TK, Chen CP, Huang CL, Huang CY, Wang MH, Huang YC, Ho HH, Chao YS, Shih JC, Tsou LK, Chen CT. Transl Oncol. 2021 Jan;14 (1):100897.
  14. Overcoming vincristine resistance in cancer: Computational design and discovery of piperine-inspired P-glycoprotein inhibitors. Syed SB, Lin SY, Arya H, Fu IH, Yeh TK, Charles MRC, Periyasamy L, Hsieh HP, Coumar MS. Chem Biol Drug Des. 2021 Jan;97(1):51-66
  15. Correction to Unique Sulfur-Aromatic Interactions Contribute to the Binding of Potent Imidazothiazole Indoleamine 2,3-Dioxygenase Inhibitors. Peng YH, Liao FY, Tseng CT, Kuppusamy R, Li AS, Chen CH, Fan YS, Wang SY, Wu MH, Hsueh CC, Chang JY, Lee LC, Shih C, Shia KS, Yeh TK, Hung MS, Kuo CC, Song JS, Wu SY, Ueng SH. J Med Chem. 2020 Jul 9;63(13):7445.
  16. Repurposing old drugs as antiviral agents for coronaviruses. Yang CW, Peng TT, Hsu HY, Lee YZ, Wu SH, Lin WH, Ke YY, Hsu TA, Yeh TK, Huang WZ, Lin JH, Sytwu HK, Chen CT, Lee SJ. Biomed J. 2020 Aug;43 (4):368-374.
  17. Artificial intelligence approach fighting COVID-19 with repurposing drugs. Ke YY, Peng TT, Yeh TK, Huang WZ, Chang SE, Wu SH, Hung HC, Hsu TA, Lee SJ, Song JS, Lin WH, Chiang TJ, Lin JH, Sytwu HK, Chen CT. Biomed J. 2020 Aug;43(4):355-362.
  18. Drug-like property optimization: Discovery of orally bioavailable quinazoline-based multi-targeted kinase inhibitors.Lin SY, Chang CF, Coumar MS, Chen PY, Kuo FM, Chen CH, Li MC, Lin WH, Kuo PC, Wang SY, Li AS, Lin CY, Yang CM, Yeh TK, Song JS, Hsu JTA, Hsieh HP. Bioorg Chem. 2020 May;98: 103689.
  19. Impacts of Intralipid on Nanodrug Abraxane Therapy and on the Innate Immune System. Chen YJ, Tsai CY, Cheng YM, Nieh SW, Yeh TK, Chen CP, Wang MH, Chou LH, Chiu TY, Liu L, Ho C, Chen CT, Liu TW. Sci Rep. 2020 Feb 18;10 (1):2838.
  20. Unique Sulfur-Aromatic Interactions Contribute to the Binding of Potent Imidazothiazole Indoleamine 2,3-Dioxygenase Inhibitors. Peng YH, Liao FY, Tseng CT, Kuppusamy R, Li AS, Chen CH, Fan YS, Wang SY, Wu MH, Hsueh CC, Chang JY, Lee LC, Shih C, Shia KS, Yeh TK, Hung MS, Kuo CC, Song JS, Wu SY, Ueng SH. J Med Chem. 2020 Feb 27;63(4):1642-1659.
  21. Protective effects of 10, 11-dihydro-5H-dibenzo [b,f]azepine hydroxamates on vascular cognitive impairment. Kaur N, Fang YC, Lee HY, Singh A, Nepali K, Lin MH, Yeh TK, Lai MJ, Chan L, Tu YK, Banerjee S, Hu CJ, Liou JP. Eur J Med Chem. 2020 Feb 1; 187:111915..
  22. Identification of a Multitargeted Tyrosine Kinase Inhibitor for the Treatment of Gastrointestinal Stromal Tumors and Acute Myeloid Leukemia. Lin WH, Wu SY, Yeh TK, Chen CT, Song JS, Shiao HY, Kuo CC, Hsu T, Lu CT, Wang PC, Wu TS, Peng YH, Lin HY, Chen CP, Weng YL, Kung FC, Wu MH, Su YC, Huang KW, Chou LH, Hsueh CC, Yen KJ, Kuo PC, Huang CL, Chen LT, Shih C, Tsai HJ, Jiaang WT. J Med Chem. 2019 Dec 26;62(24):11135-11150.
  23. Discovery of a Furanopyrimidine-Based Epidermal Growth Factor Receptor Inhibitor (DBPR112) as a Clinical Candidate for the Treatment of Non-Small Cell Lung Cancer. Lin SY, Chang Hsu Y, Peng YH, Ke YY, Lin WH, Sun HY, Shiao HY, Kuo FM, Chen PY, Lien TW, Chen CH, Chu CY, Wang SY, Yeh KC, Chen CP, Hsu TA, Wu SY, Yeh TK, Chen CT, Hsieh HP. J Med Chem. 2019 Nov 27;62(22):10108-10123.
  24. BPR1M97, a dual mu opioid receptor/nociceptin-orphanin FQ peptide receptor agonist, produces potent antinociceptive effects with safer properties than morphine. Chao PK, Chang HF, Chang WT, Yeh TK, Ou LC, Chuang JY, Tsu-An Hsu J, Tao PL, Loh HH, Shih C, Ueng SH, Yeh SH.Neuropharmacology. 2020 Apr; 166:107678.
  25. Linker Optimization and Therapeutic Evaluation of Phosphatidylserine-Targeting Zinc Dipicolylamine-based Drug Conjugates. Liu YW, Chen YY, Hsu CY, Chiu TY, Liu KL, Lo CF, Fang MY, Huang YC, Yeh TK, Pak KY, Gray BD, Hsu TA, Huang KH, Shih C, Shia KS, Chen CT, Tsou LK. J Med Chem. 2019 Jul 11;62(13):6047-6062.
  26. Discovery of Conformational Control Inhibitors Switching off the Activated c-KIT and Targeting a Broad Range of Clinically Relevant c-KIT Mutants. Wu TS, Lin WH, Tsai HJ, Hsueh CC, Hsu T, Wang PC, Lin HY, Peng YH, Lu CT, Lee LC, Tu CH, Kung FC, Shiao HY, Yeh TK, Song JS, Chang JY, Su YC, Chen LT, Chen CT, Jiaang WT, Wu SY. J Med Chem. 2019 Apr 25;62 (8):3940-3957.
  27. Delta-opioid receptor antagonist naltrindole reduces oxycodone addiction and constipation in mice. Yang PP, Yeh TK, Loh HH, Law PY, Wang Y, Tao PL.Eur J Pharmacol. 2019 Jun 5; 852:265-273.
  28. Synthesis and evaluation of novel 7H-pyrrolo-[2,3-d]pyrimidine derivatives as potential anticancer agents. Liu YM, Chen CH, Yeh TK, Liou JP. Future Med Chem. 2019 May;11(9):959-974.
  29. A novel, potent, and orally bioavailable thiazole HCV NS5A inhibitor for the treatment of hepatitis C virus. Yeh TK, Kang IJ, Hsu TA, Lee YC, Lee CC, Hsu SJ, Tian YW, Yang HY, Chen CT, Chao YS, Yueh A, Chern JH. Eur J Med Chem. 2019 Apr 1; 167:245-268.
  30. Synthesis and biological evaluation of N-glucosyl indole derivatives as sodium-dependent glucose co-transporter 2 inhibitors. Chu KF, Song JS, Chen CT, Yeh TK, Hsieh TC, Huang CY, Wang MH, Wu SH, Yao CH, Chao YS, Lee JC. Bioorg Chem. 2019 Mar; 83:520-525.

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