Researcher Profile

Researcher Profile

Arun Sharma, PhD

Arun Sharma, PhD

Associate Professor, Department of Pharmacology
Scientific Program:Experimental Therapeutics
aks14@psu.edu

Research Interests

The major focus of Dr. Arun Sharma’s lab is the design and development of novel small drug-like molecules as potential cancer therapeutic and preventive agents, and testing them in various in vitro and in vivo cancer models.

This effort has resulted in the development of some potent anti-cancer agents and understanding of their efficacy, toxicity, pharmacokinetics, and mechanisms of action. The main strategies adapted for designing new agents include optimization of

  • naturally occurring agents;
  • existing drugs or agents that fail in clinical trials; and
  • lead compounds obtained from chemical library screening, to enhance potency, bioavailability and therapeutic/chemopreventive index.

An example of natural product optimization includes the development of ISC-4, an isosteric selenium analog of isothiocyanates that occur naturally in cruciferous vegetables. ISC-4 was shown to be a PI3K/Akt pathway inhibitor that effectively inhibited tumor growth in melanoma and colon cancer xenograft models, alone and in combination with standard of care. Further optimization of ISC-4 structure has now led to a dual Akt pathway/topoisomerase II inhibitor NISC-6 as a potential melanoma therapeutic.

Through extensive structure-activity studies based on Selenium-NSAID hybrid molecules, Dr. Sharma’s lab has recently discovered two potent small molecules: Se-Aspirin, published recently and already commercially available; and AS-10, a bis-aspirinyl-selenazolidine analog which has shown great potential as a cancer therapeutic, particularly for pancreatic cancer. p-XS-Asp, another Se-aspirin hybrid molecule developed recently, is orally bioavailable and effective in preventing against NNK induced lung tumorigenesis.

Apart from developing anti-cancer compounds, Dr. Sharma’s lab is also focusing on developing "smart antibiotics." The emphasis is on designing and synthesizing cationic bolaamphiphiles (CABs) as carrier compounds that can transport antisense oligonucleotide (ASO) into C. difficile to selectively target the genetic material in C. difficile.

  • Neoplasms
  • Cell Line
  • Therapeutics
  • Melanoma
  • Growth
  • Cycloaddition Reaction
  • Apoptosis
  • Selenium
  • Peroxisome Proliferator-Activated Receptors
  • Environmental Pollutants
  • Ligands
  • Pyrimidinones

Recent Publications

2019

Narayan, S, Ramisetti, S, Jaiswal, AS, Law, BK, Singh-Pillay, A, Singh, P, Amin, S & Sharma, A 2019, 'ASR352, A potent anticancer agent: Synthesis, preliminary SAR, and biological activities against colorectal cancer bulk, 5-fluorouracil/oxaliplatin resistant and stem cells', European Journal of Medicinal Chemistry, vol. 161, pp. 456-467. https://doi.org/10.1016/j.ejmech.2018.10.052
Frieben, EE, Amin, S & Sharma, A 2019, 'Development of Isoselenocyanate Compounds' Syntheses and Biological Applications', Journal of Medicinal Chemistry, vol. 62, no. 11, pp. 5261-5275. https://doi.org/10.1021/acs.jmedchem.8b01698
Alcolea, V, Karelia, DN, Pandey, MK, Plano, D, Singh, P, Palop, JA, Amin, S, Sanmartín, C & Sharma, A 2019, 'Identification of a novel quinoxaline-isoselenourea targeting the STAT3 pathway as a potential melanoma therapeutic' International journal of molecular sciences, vol. 20, no. 3, 521. https://doi.org/10.3390/ijms20030521
Fernández-Rubio, C, Larrea, E, Guerrero, JP, Herrero, ES, Gamboa, I, Berrio, C, Plano, D, Amin, S, Sharma, A & Nguewa, PA 2019, 'Leishmanicidal activity of isoselenocyanate derivatives', Antimicrobial agents and chemotherapy, vol. 63, no. 2, e00904-18. https://doi.org/10.1128/AAC.00904-18

2018

Sharma, A, Krzeminski, J, Weissig, V, Hegarty, JP & Stewart, DB 2018, 'Cationic amphiphilic bolaamphiphile-based delivery of antisense oligonucleotides provides a potentially microbiome sparing treatment for C. difficile', Journal of Antibiotics, vol. 71, no. 8, pp. 713-721. https://doi.org/10.1038/s41429-018-0056-9
Ruberte, AC, Plano, D, Encío, I, Aydillo, C, Sharma, A & Sanmartín, C 2018, 'Novel selenadiazole derivatives as selective antitumor and radical scavenging agents', European Journal of Medicinal Chemistry, vol. 157, pp. 14-27. https://doi.org/10.1016/j.ejmech.2018.07.063
Wu, W, Karelia, D, Pramanik, K, Amin, S, Sharma, A, Jiang, C & Lu, J 2018, 'Phenylbutyl isoselenocyanate induces reactive oxygen species to inhibit androgen receptor and to initiate p53-mediated apoptosis in LNCaP prostate cancer cells', Molecular Carcinogenesis, vol. 57, no. 8, pp. 1055-1066. https://doi.org/10.1002/mc.22825
Pal, D, Tyagi, A, Chandrasekaran, B, Alattasi, H, Ankem, MK, Sharma, A & Damodaran, C 2018, 'Suppression of Notch1 and AKT mediated epithelial to mesenchymal transition by Verrucarin J in metastatic colon cancer', Cell Death and Disease, vol. 9, no. 8, 798. https://doi.org/10.1038/s41419-018-0810-8
Chandrasekaran, B, Pal, D, Kolluru, V, Tyagi, A, Baby, B, Dahiya, NR, Youssef, K, Alatassi, H, Ankem, MK, Sharma, A & Damodaran, C 2018, 'The chemopreventive effect of withaferin A on spontaneous and inflammation-associated colon carcinogenesis models', Carcinogenesis, vol. 39, no. 12, pp. 1537-1547. https://doi.org/10.1093/carcin/bgy109

2017

Ramisetti, SR, Oña-Ruales, JO, Wise, SA, Amin, S & Sharma, A 2017, 'An Efficient Synthesis of Dibenzo[a,l]tetracene and Dibenzo[a,j]tetracene and Their Identification in a Coal Tar Extract' Polycyclic Aromatic Compounds, pp. 1-11. https://doi.org/10.1080/10406638.2017.1362013
Ramisetti, SR, Pandey, MK, Lee, S, Karelia, D, Narayan, S, Amin, S & Sharma, A 2018, 'Design and synthesis of novel thiobarbituric acid derivatives targeting both wild-type and BRAF-mutated melanoma cells', European Journal of Medicinal Chemistry, vol. 143, pp. 1919-1930. https://doi.org/10.1016/j.ejmech.2017.11.006
Karelia, DN, Sk, UH, Singh, P, Gowda, ASP, Pandey, MK, Ramisetti, SR, Amin, S & Sharma, A 2017, 'Design, synthesis, and identification of a novel napthalamide-isoselenocyanate compound NISC-6 as a dual Topoisomerase-IIα and Akt pathway inhibitor, and evaluation of its anti-melanoma activity', European Journal of Medicinal Chemistry, vol. 135, pp. 282-295. https://doi.org/10.1016/j.ejmech.2017.04.052
Plano, D, Alcolea, V, Sanmartín, C & Sharma, A 2017, 'Methods of selecting combination therapy for colorectal cancer patients: a patent evaluation of US20160025730A1', Expert Opinion on Therapeutic Patents, vol. 27, no. 5, pp. 527-538. https://doi.org/10.1080/13543776.2017.1315103
Chandrasekaran, B, Tyagi, A, Sharma, A, Cai, L, Ankem, M & Damodaran, C 2017, 'Molecular insights: Suppression of EGFR and AKT activation by a small molecule in non-small cell lung cancer', Genes and Cancer, vol. 8, no. 9-10, pp. 713-724. https://doi.org/10.18632/genesandcancer.154
Narayan, S, Jaiswal, AS, Sharma, R, Nawab, A, Duckworth, LV, Law, BK, Zajac-Kaye, M, George, TJ, Sharma, J, Sharma, A & Hromas, RA 2017, 'NSC30049 inhibits Chk1 pathway in 5-FU-resistant CRC bulk and stem cell populations', Oncotarget, vol. 8, no. 34, pp. 57246-57264. https://doi.org/10.18632/oncotarget.19778

2016

Hegarty, JP, Krzeminski, J, Sharma, A, Guzman-Villanueva, D, Weissig, V & Stewart, D 2016, 'Bolaamphiphile-based nanocomplex delivery of phosphorothioate gapmer antisense oligonucleotides as a treatment for Clostridium difficile', International Journal of Nanomedicine, vol. 11, pp. 3607-3619. https://doi.org/10.2147/IJN.S109600
Alcolea, V, Plano, D, Encío, I, Palop, JA, Sharma, A & Sanmartín, C 2016, 'Chalcogen containing heterocyclic scaffolds: New hybrids with antitumoral activity', European Journal of Medicinal Chemistry, vol. 123, pp. 407-418. https://doi.org/10.1016/j.ejmech.2016.07.042
Plano, D, Karelia, DN, Pandey, MK, Spallholz, JE, Amin, S & Sharma, A 2016, 'Design, Synthesis, and Biological Evaluation of Novel Selenium (Se-NSAID) Molecules as Anticancer Agents', Journal of Medicinal Chemistry, vol. 59, no. 5, pp. 1946-1959. https://doi.org/10.1021/acs.jmedchem.5b01503
Kaur, G, Mahajan, MP, Pandey, MK, Singh, P, Ramisetti, SR & Sharma, A 2016, 'Design, synthesis, and anti-breast cancer evaluation of new triarylethylene analogs bearing short alkyl- and polar amino-/amido-ethyl chains', Bioorganic and Medicinal Chemistry Letters, vol. 26, no. 8, pp. 1963-1969. https://doi.org/10.1016/j.bmcl.2016.03.008
Narayan, S, Jaiswal, AS, Law, BK, Kamal, MA, Sharma, A & Hromas, RA 2016, 'Interaction between APC and Fen1 during breast carcinogenesis' DNA Repair, vol. 41, pp. 54-62. https://doi.org/10.1016/j.dnarep.2016.04.003
Alcolea, V, Plano, D, Karelia, DN, Palop, JA, Amin, S, Sanmartín, C & Sharma, A 2016, 'Novel seleno- and thio-urea derivatives with potent in vitro activities against several cancer cell lines', European Journal of Medicinal Chemistry, vol. 113, pp. 134-144. https://doi.org/10.1016/j.ejmech.2016.02.042

2015

Oña-Ruales, JO, Sharma, A & Wise, SA 2015, 'Identification and quantification of six-ring C26H16 cata-condensed polycyclic aromatic hydrocarbons in a complex mixture of polycyclic aromatic hydrocarbons from coal tar', Analytical and Bioanalytical Chemistry, vol. 407, no. 30, pp. 9165-9176. https://doi.org/10.1007/s00216-015-9084-5
Dick, TE, Hengst, J, Fox, TE, Colledge, AL, Kale, VP, Sung, S, Sharma, A, Amin, S, Loughran, TP, Kester, M, Wang, H-G & Yun, J 2015, 'The apoptotic mechanism of action of the sphingosine kinase 1 selective inhibitor SKI-178 in human acute myeloid leukemia cell lines' Journal of Pharmacology and Experimental Therapeutics, vol. 352, no. 3, pp. 494-508. https://doi.org/10.1124/jpet.114.219659

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