July 19, 2019

Brendan Frett, Ph.D.

Assistant Professor of Pharmaceutical Sciences
UAMS College of Pharmacy

Research Interest Statement

Dr. Frett’s research focuses on small molecule drug design and developing enabling chemical methodologies to expedite the drug discovery process. In particular, he is interested in generating small molecules that have been strategically designed to modulate two or more targets in a given disease. Because of heterogeneity within cancer, multi-targeted approaches are of particular interest to extended cancer remissions to precision medicine. Dr. Frett examines the design of new therapies in the context of both the tumor and the tumor microenvironment to identify comprehensive approaches to target malignances.

Furthermore, Dr. Frett is investigating strategies to mitigate side effects to radiotherapy. Analogous to signaling within the tumor, radiation treatment activates a variety of deleterious processes in normal tissue. Using a similar, multi-targeted approach, Dr. Frett is designing countermeasures to limit radiation damage to normal tissue.

Dr. Frett’s Grants

NCI – 1 R41 CA224830

Preclinical studies of selective and orally bioavailable Aurora B inhibitors for the treatment of AML

07/03/2018 – 01/02/2020

Role: PI (Multi-PI with Hong Yu-Li, PhD [UAMS] and Monica Guzman, PhD [Weill Cornell Medical College]

Recipient Organization: Synactix Pharmaceuticals, Inc.

$299,975*

 

American Thyroid Association

Dual Inhibition of RET and Aurora B to Study the Simultaneous Regulation of Multiple Oncogene Pathways in Medullary Thyroid Cancer

07/01/2018 – 06/30/2020

$25,000*

 

UAMS College of Pharmacy Seed Grant

Simultaneous Control of Multiple Oncogenes with a Single Molecule: Proof of Concept Studies in Thyroid Cancer

10/1/2018 – 9/30/2019

$16,200*

 

UAMS Foundation/Medical Research Endowment

Development of Molecular Tools to Simultaneously Control Catalytic Activity and Expression Profiles of Oncogene Products

01/01/2019 -12/31/2019

$15,000*

 

UAMS Winthrop P. Rockefeller Cancer Institute Seeds of Science Small Grant

B. Frett, Ph.D., and S. Kendrick, Ph.D.

PROTAC Strategies to Target the Multifaceted Nek2 Kinase in Lymphoma and other Malignancies

02-01-2019 to 01-31-2020

$50,000*

*cancer-related annual direct costs

Dr. Frett’s UAMS Collaborators

Samantha Kendrick, Ph.D., Department of Biochemistry and Molecular Biology

Aime T. Franco, Ph.D., Department of Physiology and Biophysics

Dr. Frett’s External Collaborators

Monica Guzman, Ph.D., Weill Cornell Medical College

Bilal Bin Hafeez, Ph.D., University of Texas Rio Grande Valley

Opportunities for Collaboration

I am eager for opportunities to collaborate with colleagues at UAMS. My scientific expertise is in medicinal chemistry, which can be useful in identifying novel cancer biology or innovative therapies. I encourage anyone to stop by to discuss new ideas, projects or collaborations.

You May Not Know That …

I am an amateur horologist and animal lover. From time to time, you may see me running around Little Rock with my two dogs.

Recent Cancer-Related Publications

Saha, D.; Kharbanda, A.; Essien, N.; Zhang, L.; Cooper, R.; Basak, D.; Kendrick, S.; Frett, B.*; Li, H. Intramolecular cyclization of imidazo[1,2-a]pyridine via a silver mediated/palladium catalyzed C-H activation strategy. Org. Chem. Front. (2019), 6 (13), 2234-2239.

Naresh, G.; Kharbanda, A.; Lakkaniga, N.R.; Zhang, L.; Cooper, R.; Li, H.; Frett, B.* Catalyst free, C-3 Functionalization of Imidazo[1,2-a]pyridines to Rapidly Access New Chemical Space for Drug Discovery Efforts, ChemComm (2018) DOI: 10.1039/C8CC07063F

Wei, Y.; Lakkaniga, N.R.; Carlomagno, F.; Santoro, M.; McDonald, N.; Lv, F.; Naresh, G.; Frett, B.*; Li, H. Insights into Current Tropomyosin Receptor Kinase (TRK) Inhibitors: Development and Clinical Application, J Med Chem (2018) DOI: 10.1021/acs.jmedchem.8b01092

Song, G.T.; McConnell N.; Chen, Z.; Yao, X.F.; Huang, J.H.; Lei, J.; Zhu, J.; Lin, H.K.; Frett, B.; Li, H.; Xu, Z. Diversity-Oriented Synthesis of Functionalized Imidazopyridine Analogues with Anti-cancer Activity through a Transition-Metal Free, One-Pot Cascade Reaction, Adv. Synth. Catal. (2018). https://doi.org/10.1002/adsc.201800728

He, L.J.; Yang, D.L.; Li, S.Q.; Zhang, Y.J.; Tang, Y.; Lei, J.; Frett, B.; Lin, H.K.; Li, H.; Chen, Z.Z.; Xu, Z. Facile construction of fused benzimidazole-isoquinolinones that induce cell-cycle arrest and apoptosis in colorectal cancer cells, Bioorganic & Medicinal Chemistry (2018). https://doi.org/10.1016/j.bmc.2018.06.010

Bharate, J.B.; McConnell, N.; Naresh, G.; Zhang, L.; Lakkaniga, N.R.; Ding, L.; Shah, N.P.; Frett, B.; Li, H. Rational Design, Synthesis and Biological Evaluation or Pyrimidine-4,6-diamine derivative as Type-II inhibitors of FLT3 Selective Against c-KIT, Sci. Rep (2018) 8, 3722.

Wang, J.; Cheng, P.; Pavliukov, M.S.; Zhang, Zhuo; Kim, S.-H.; Minata, M.; Mohyeldin, A.; Xie, W.; Chen, D.; Goidts, V.; Frett, B.; Hu, W.; Li, H.; Shin, Y.J.; Lee, Y.; Nam, D.H.; Wang, M.D.; Nakano, I. Targeting NEK2 attenuates glioblastoma growth and radio-resistance viade-stabilizing EZH2, J. Clin. Invest. (2017) 127, 3075-3089.

Xi J.; Fang, Y.; Frett, B.*; Zhu, M.-L.; Zhu, T.; Kong, Y.-N.; Guan, F.-J.; Zhao, Y.; Zhang, X.-W.; Li, H.; Ma, M.; Hu, W., Structure-based design and synthesis of imidazo[1,2-a]pyridine derivatives as novel and potent Nek2 inhibitors with in vitro and in vivo antitumor activities, Eur. J. Med. Chem. (2017) 126, 1083-1106.