Aarajana Shrestha
Dr. Shrestha is a pharmaceutical research scientist/manager experienced in the modification of a wide range of enzymes and receptors (including topoisomerase, PPARd, EWS-FLI1, and 4E-BP1) inhibitors to improve their potency and ADME profile. Her previous research was focused on the areas of chemical probes/small molecules, natural product drug discovery, and optimization of novel drugs for cancer and rare diseases. Prior to joining Larkin University, she was a postdoctoral scholar working with Dr. Jon Thorson at the Center for Pharmaceutical Research and Innovation, College of Pharmacy University of Kentucky. Dr. Shrestha holds a B. Pharm. from Pokhara University, Nepal, and an MS and PhD in Medicinal Chemistry from Yeungnam University College of Pharmacy, South Korea. From 2020 to 2021, she was National Research Foundation-Korea Research Fellow (KRF Fellow) as a drug discovery chemist at the New Drug Development Center DGMIF, K-MEDIhub. Dr. Shrestha holds 1 US patent, over 30 peer-reviewed scientific publications, and has presented her research at several conferences, including the American Chemical Society, the Gordon Research Conference, and IUPAC.
Education and Training
2021–2024: Postdoctoral Scholar (Advisor: Dr. Jon Thorson) The Center for Pharmaceutical Research and Innovation, College of Pharmacy University of Kentucky 2020–2021: NRF Research Fellow, K-MEDI hub New Drug Development Center, South Korea
2019–2020: Postdoctoral Researcher, Institute for Drug Research, Yeungnam University, South Korea
2014–2019: MS & PhD in Medicinal Chemistry (Advisor: Dr. Eung-Seok Lee), Yeungnam University College of Pharmacy, South Korea
2009–2014: B. Pharm, Pokhara University, Central Institute of Science and Technology, Nepal
Research and Scholarly Interests
Dr. Shrestha’s research is focused on the areas of chemical probes/small molecules, natural product drug discovery, and optimization of novel drugs for cancer and rare diseases. She has contributed to several interdisciplinary drug discovery teams by doing inventory management, lab management, developing standard operating procedures, ensuring compliance with safety regulations, strategic planning, patent and paper writing, mentoring undergraduate/graduate students, record keeping of experimental data using CDD and E-notebook, presenting data in department/team meetings and conferences. At Larkin University, Dr. Shrestha is dedicated to fostering collaborations that integrate computational and lab-based techniques to address complex research challenges. Additionally, she has a strong passion for various scholarly activities, with a particular focus on advancing health science education and research by promoting curiosity, creativity, inclusivity, and securing external funding opportunities.
Patent and Publications
- Total 33 Publications in peer-reviewed journals, 11 First Author, Google Scholar Citation: 732
- >7 Lectures, 11 Posters
- Co-inventor on 1 U.S. patent application
PATENT
Aarajana Shrestha, Yang Liu, Mark Leggas, Jon Thorson, Mithramycin (MTM) 2’ Oximes”. US Patent Application 63,496,407 (2024)
SELECTED PUBLICATIONS (*equal contributor)
1. Shrestha A, Liu Y, Leggas M, Thorson JS. “Discovery and Optimization of Mithramycin 2’-oximes Targeting EWS-FLI1 Transcription Factor to Treat Ewing Sarcoma” (2025) In Progress.
2. Shrestha A, Hwang SY, Kunwar S, Kadayat TM, Park S, Liu Y, Jo H, Sheen N, Seo M, Lee ES, Kwon Y “Di-indenopyrimidines as topoisomerase II-selective anticancer agents: Design, synthesis, and structure-activity relationships” Bioorg. Med. Chem. 91 (2023), 117403. Link
3. Hwang SY, Shrestha A*, Park S, Bist G, Kunwar S, Kadayat TM, Jang H, Seo M, Sheen N, Kim S, Jeon KH, Lee ES, Kwon Y “Identification of new halogen-containing 2,4-diphenyl indenopyridin-5-one derivative as a boosting agent for the anticancer responses of clinically available topoisomerase inhibitors” Eur. J. Med. Chem. 227 (2022), 113916. Link
4. Kunwar S, Lee SM, Shrestha A, Park P H, Lee ES “Potent inhibitory activity of hydroxylated 2-benzylidene-3, 4-dihydronaphthalen-1 (2H)-ones on LPS-stimulated reactive oxygen species production in RAW 264.7 macrophages” Bioorg. Med. Chem. Lett. 73 (2022), 128921. Link
5. Shrestha A, Kim N, Lee SJ, Jeon YH, Song JJ, An H, Cho SJ, Kadayat TM, Chin J “Targeting NSD Family of Histone Lysine Methyltransferases: Recent Progress and Perspective” J. Med. Chem. 64 (2021), 14913-14929 Link
6. Kadayat TM, Kim DE, Lee SB, Jung K, park SE, Hong JY, Kim J, Shrestha A, Kim DS, An H, Kim N, Hwang JJ, Cho SJ, Chin J “Antioxidative and Anti-inflammatory activity of Psiguadial B and its halogenated analogues as potential neuroprotective agents” Bioorg. Chem. 113 (2021), 105027. Link
7. Kadayat TM, Shrestha A*, Jeon YH, Kim J, An H, Cho SJ, Chin J Targeting Peroxisome Proliferator-activated Receptor delta (PPARd) agonist: A Medicinal Chemistry Perspective J. Med. Chem. 63 (2020), 10109-10134. Link
8. Shrestha A, Kadayat TM Drug Discovery and Development Strategies for COVID-19 Europasian J. Med. Sci. 2 (2020), 1-5. Link
9. Kadayat TM, Park S, Shrestha A, Jo H, Hwang SY, Katila P, Kwon Y, Lee ES Discovery and Biological Evaluations of Halogenated 2,4-Diphenyl Indeno[1,2-b]pyridinol Derivatives as Potent Topoisomerase IIα-targeted Chemotherapeutic Agents for Breast Cancer J. Med. Chem. 62 (2019), 8194-8234. Link
10. Shrestha A, Park S, Shin S, Kadayat TM, Bist G, Katila P, Kwon Y, Lee ES Design, synthesis, biological evaluation, structure-activity relationship study, and mode of action of 2-phenol-4,6-dichlorophenyl-pyridines Bioorg. Chem. 79 (2018), 1-18. Link
11. Shrestha A, Jo H, Kwon Y, Lee ES Design, synthesis, and structure-activity relationships of new benzofuro[3,2-b]pyridin-7-ols as DNA topoisomerase II inhibitors Bioorg. Med. Chem. Lett. 28 (2018), 566-571. Link
12. Shrestha A, Park S, Jang HJ, Katila P, Shrestha R, Kwon Y, Lee ES A new phenolic series of indenopyridinone as topoisomerase inhibitors: Design, synthesis, and structure-activity relationships Bioorgan. Med. Chem. 26 (2018), 5212-5223. Link
13. Shrestha A, Oh HJ, Kim MJ, Pun NT, Thapa Magar TB, Bist G, Choi HS, Park PH, Lee ES Design, synthesis, and structure-activity relationship study of halogen containing 2-benzylidene-1-indanone derivatives for inhibition of LPS-stimulated ROS production in RAW 264.7 macrophages Eur. J. Med. Chem. 133 (2017), 121-138. Link
14. Shrestha A, Park PH, Lee ES Hydroxyl- and Halogen-containing Chalcones for the
Inhibition of LPS-stimulated ROS Production in RAW 264.7 Macrophages: Design, Synthesis and Structure–Activity Relationship Study Bull. Korean Chem. Soc. 40 (2018), 729-734. Link
15. Jeon KH, Park C, Kadayat TM, Shrestha A, Lee ES, Kwon Y A novel indeno[1,2-b]pyridinone derivative, a DNA intercalative human topoisomerase IIa catalytic inhibitor, for caspase 3-independent anticancer activity Chem. Commun. 53 (2017), 6864-6867. Link
16. Thapa RK, Nguyen HT, Gautam M, Shrestha A, Lee ES, Ku SK, Choi HG, Yong CS, Kim JO Hydrophobic binding peptide-conjugated hybrid lipid-mesoporous silica nanoparticles for effective chemo-photothermal therapy of pancreatic cancer Drug Deliv. 24 (2017), 1690-1702. Link
17. Bist G, Park S, Song C, Thapa Magar TB, Bist G, Shrestha A, Kwon Y, Lee ES Dihydroxylated 2,6-diphenyl-4-chlorophenylpyridines: Topoisomerase I and IIa dual inhibitors with DNA non-intercalative catalytic activity Eur. J. Med. Chem. 133 (2017), 69-84. Link
18. Kadayat TM, Banskota S, Gurung P, Bist G, Thapa Magar TB, Shrestha A, Kim JA, Lee ES Discovery and structure-activity relationship studies of 2- benzylidene-2,3-dihydro-1H-inden-1-one and benzofuran-3(2H)-one derivatives as a novel class of potential therapeutics for inflammatory bowel disease Eur. J. Med. Chem. 137 (2017), 575-597. Link 19. Kadayat TM, Park S, Jun K-Y, Magar TBT, Bist G, Shrestha A, Na Y, Kwon Y, Lee ES Novel 2-aryl-4-(4′-hydroxyphenyl)-5H-indeno [1, 2-b] pyridines as potent DNA non-intercalative topoisomerase catalytic inhibitors Eur. J. Med. Chem. 125 (2017), 14-28.
20. Thapa P, Kadayat TM, Park S, Shin S, Magar TBT, Bist G, Shrestha A, Na Y, Kwon Y, Lee ES “Synthesis and biological evaluation of 2-phenol-4-chlorophenyl-6-aryl pyridines as topoisomerase II inhibitors and cytotoxic agents” Bioorg. Chem. 66 (2016), 145-159.
21. Karki R, Song C, Kadayat TM, Thapa Magar TB, Bist G, Shrestha A, Na Y, Kwon Y, Lee ES “Topoisomerase I and II inhibitory activity, cytotoxicity, and structure-activity relationship study of dihydroxylated 2,6-diphenyl-4-aryl pyridines” Bioorg. Med. Chem. 23 (2015), 3638-3658.
For complete list of published work: PubMed: https://pubmed.ncbi.nlm.nih.gov/?term=aarajana%20shrestha&sort=date&ac=yes
Selected Oral Presentations and Invited Lectures
1. Shrestha A, Mithramycin-Oxime AK-B46 for Treating Children Cancer. Global Korea Scholarship (GKS) Alumni Nepal Symposium (Nov 10, 2024, Kathmandu, Nepal).
2. Shrestha A, Discovery of AK-B46 for the treatment of bone cancer in children and younger adults. Society of Postdoctoral Scholar Annual Research Talk Competition (Sept 18, 2024, Lexington USA).
3. Shrestha A, Gordon Research Conference-High Throughput Chemistry and Chemical Biology (July 30 – August 4, 2023, New London, NH, USA).
4. Shrestha A, Gordon Research Seminar-Medicinal Chemistry (August 5-6, 2023, New London, NH, USA).
5. Shrestha A, Leggas M, Thorson JS. Optimization of Mithramycin 2’-oximes targeting EWS-FLI1 transcription factor to treat Ewing Sarcoma. 2023 Therapeutics Outcomes Discovery & Delivery (TODD) Symposium (April 12, 2023, Lexington, KY, USA)
6. Shrestha A, Discovery of Flexible and Rigid Analogues of Trisubstituted Pyridine as Topoisomerase Inhibitors. Kathmandu University Pharma Symposium (Dec 19, 2019 Kathmandu, Nepal).
7. Shrestha A, Design and Synthesis of 2,4-Diphenyl-5H-indeno[1,2-b]pyridin-5-ones as novel topoisomerase targeted antiproliferative agents. 47th IUPAC World Chemistry Congress (July 6-11, 2019, Paris, France).
8. Shrestha A, Synthesis of halogen containing 2-benzylidene-1-indanones for inhibition of ROS production 11th AFMC International Medicinal Chemistry Congress, (Oct 21-25, 2017, Melbourne, Australia).
9. Shrestha A, Synthesis of Chlorinated 2,4,6- Triphenyl Pyridines as Topoisomerase I and II Inhibitors, 10th AFMC International Medicinal Chemistry Congress (Oct 15-19, 2015, Jeju, South Korea).
Awards and Honors
2023 Gordon Research Seminar in Medicinal Chemistry, $500 travel award
2020 Korea Research Fellowship 2020 by Korea Ministry of Science and ICT, ~$40,000
2019 IUPAC World Chemistry Congress 2019, Paris, France, ~$2,000 travel grant
2016 Yeungnam University Outstanding International Student’s Scholarship, ~$16,000
2014 10th Symposium of Pharmaceutical Society of Korea, Medicinal Chemistry, Young Scientist Best Presentation Award, ~$200 travel award
2014 Pokhara University Dean’s Award 2014
2011 CIST College Excellent Student Scholarship 2011
Research Fellowship Award
National Research Foundation-Korea Research Fellowship (KRF-2020H1D3A1A02081263) by the Korea Ministry of Science and ICT (2020–2022); Research Title: Rational design of hybrid inhibitors and maximizing their target proteins-degrading abilities using in-situ biorthogonal reactions; Fund: ~US$ 160,000
Scholarly and Professional Services
1. Vice-President (2023-2024), University of Kentucky Society of Postdoctoral Scholars (UK SOPS). Planned and executed SOPS annual activities.
2. Reviewer (2022-Current), Bioorg. Chem.; Bioorg. Med. Chem. Lett. 3. Editor (2019-2021), Europasian J. Med. Sci.
4. Coordinator (2018-2019), Korea Woman Scientists and Engineers, Smart Sister Program. Organized networking and professional development events for young women in science.
5. Lab Manager (2017-2019), Institute of Drug Research, Yeungnam University, South Korea
6. President (2016-2017), Society of Nepalese Students in Korea (SONSIK). Integrated, represented, and empowered >1,000 Nepalese students and scholars to in South Korea.
7. Member (2014-Current), American Chemical Society
