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Personal profile

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.

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  • 12 Similar Profiles
Cycloaddition Chemical Compounds
Metabolites Chemical Compounds
Cells Chemical Compounds
Cell Line Medicine & Life Sciences
Pyrimidinones Chemical Compounds
Cycloaddition Reaction Medicine & Life Sciences
Neoplasms Medicine & Life Sciences
Peroxisome Proliferator-Activated Receptors Medicine & Life Sciences

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Projects 2009 2021

gemcitabine
Pancreatic Neoplasms
Adenocarcinoma
Therapeutics
Heterografts
Molecular Probes
Dopamine D1 Receptors
Ligands
Single-Photon Emission-Computed Tomography
Catechols
Infection
Anti-Bacterial Agents
Therapeutics
Bacteria
bolaamphiphile

A novel compound for colorectal cancer prevention

Sharma, A. & Sharma, A. K.

National Institutes of Health

7/11/143/31/17

Project: Research project

Aspirin
Colorectal Neoplasms
Hydrogen Cyanide
Inbred F344 Rats
Carcinogenesis
Lung Neoplasms
Aspirin
Hydrogen Cyanide
Anti-Inflammatory Agents
Pharmaceutical Preparations

Research Output 1993 2019

  • 2386 Citations
  • 28 h-Index
  • 96 Article
  • 3 Review article

ASR352, A potent anticancer agent: Synthesis, preliminary SAR, and biological activities against colorectal cancer bulk, 5-fluorouracil/oxaliplatin resistant and stem cells

Narayan, S., Ramisetti, S., Jaiswal, A. S., Law, B. K., Singh-Pillay, A., Singh, P., Amin, S. & Sharma, A., Jan 1 2019, In : European Journal of Medicinal Chemistry. 161, p. 456-467 12 p.

Research output: Contribution to journalArticle

oxaliplatin
Bioactivity
Stem cells
Fluorouracil
Antineoplastic Agents
1 Citation (Scopus)

Development of Isoselenocyanate Compounds' Syntheses and Biological Applications

Frieben, E. E., Amin, S. & Sharma, A., Jun 13 2019, In : Journal of Medicinal Chemistry. 62, 11, p. 5261-5275 15 p.

Research output: Contribution to journalArticle

Sulfur
Isothiocyanates
Neoplasms
Organoselenium Compounds
Glucosinolates

Identification of a novel quinoxaline-isoselenourea targeting the STAT3 pathway as a potential melanoma therapeutic

Alcolea, V., Karelia, D. N., Pandey, M. K., Plano, D., Singh, P., Palop, J. A., Amin, S., Sanmartín, C. & Sharma, A., Feb 1 2019, In : International journal of molecular sciences. 20, 3, 521.

Research output: Contribution to journalArticle

quinoxalines
STAT3 Transcription Factor
Quinoxalines
Transcription
Transducers
1 Citation (Scopus)

Leishmanicidal activity of isoselenocyanate derivatives

Fernández-Rubio, C., Larrea, E., Guerrero, J. P., Herrero, E. S., Gamboa, I., Berrio, C., Plano, D., Amin, S., Sharma, A. & Nguewa, P. A., Feb 1 2019, In : Antimicrobial agents and chemotherapy. 63, 2, e00904-18.

Research output: Contribution to journalArticle

Leishmania major
Leishmaniasis
Leishmania
Amphotericin B
Cell Cycle
2 Citations (Scopus)

Cationic amphiphilic bolaamphiphile-based delivery of antisense oligonucleotides provides a potentially microbiome sparing treatment for C. difficile

Sharma, A., Krzeminski, J., Weissig, V., Hegarty, J. P. & Stewart, D. B., Aug 1 2018, In : Journal of Antibiotics. 71, 8, p. 713-721 9 p.

Research output: Contribution to journalArticle

Antisense Oligonucleotides
Microbiota
Escherichia coli
Infection
Dysbiosis