Brendan A. Frett, PhD

Research Program: Developmental Therapeutics Faculty Rank: Assistant Professor Campus: University of Arkansas for Medical Sciences College: College of Pharmacy Department: Pharmaceutical Sciences

Cancer Research Interest

• Disease Site Focus: No Specific Disease Site
• Research Focus Area: Prevention, Treatment, Detection
• Type of Research: Basic
• Research Interest Statement: My cancer research efforts pertain to the design and development of multi-targeted drugs that more effectively control cancerous growth. This includes targeting the tumor, as well as the tumor microenvironment, to deter tumor growth and facilitate tumor removal. We are also actively involved in the development of therapeutic strategies to limit side effects of radio and chemotherapy. Projects completed in our laboratory are highly translational, and we believe in the mantra 'from bench to bedside'.

Contact Information

• Email Address: BAFrett@uams.edu
• Profiles Research Networking Software: View Profile

Active Grants

• NIH/Nat. Inst. of General Medical Sciences – 2P20GM109005
  “CONCURRENT TNF-ALPHA AND TGF-BETA IMPAIRMENT TO LIMIT RADIOTHERAPY-INDUCED PULMONARY FIBROSIS”
  Principal Investigator
  08/17/20 – 05/31/25

Publications

• Acharya B, Miah S, Frett B. Targeting TGF-?: triumphs and challenges. Future medicinal chemistry. 2022. PMID: 35152715.
• Zhang L, Moccia M, Briggs DC, [et al., including Frett B]. Discovery of N-Trisubstituted Pyrimidine Derivatives as Type I RET and RET Gatekeeper Mutant Inhibitors with a Novel Kinase Binding Pose. Journal of medicinal chemistry. 2022 65(2):1536-1551. PMID: 35081714.
• Zhang L, Lakkaniga NR, Bharate JB, [et al., including Frett B]. Discovery of imidazo[1,2-a]pyridine-thiophene derivatives as FLT3 and FLT3 mutants inhibitors for acute myeloid leukemia through structure-based optimization of an NEK2 inhibitor. European journal of medicinal chemistry. 2021 225:113776. PMID: 34479037.
• Saha D, Ryan KR, Lakkaniga NR, [et al., including Frett B]. Targeting Rearranged during Transfection in Cancer: A Perspective on Small-Molecule Inhibitors and Their Clinical Development. Journal of medicinal chemistry. 2021. PMID: 34402300.
• Kharbanda A, Tran P, Zhang L, [et al., including Frett B]. Discovery of 4-aminoquinolines as highly selective TGF?R1 inhibitors with an attenuated MAP4K4 profile for potential applications in immuno-oncology. European journal of medicinal chemistry. 2021 225:113763. PMID: 34419892.
• Moccia M, Yang D, Lakkaniga NR, [et al., including Frett B]. Targeted activity of the small molecule kinase inhibitor Pz-1 towards RET and TRK kinases. Scientific reports. 2021 11(1):16103. PMID: 34373541. PMCID: PMC8352932.
• Kharbanda A, Zhang L, Saha D, [et al., including Frett B]. Discovery and biological evaluation of phthalazines as novel non-kinase TGF? pathway inhibitors. European journal of medicinal chemistry. 2021 223:113660. PMID: 34246853.
• Yan W, Zhang L, Lv F, [et al., including Frett B]. Discovery of pyrazolo-thieno[3,2-d]pyrimidinylamino-phenyl acetamides as type-II pan-tropomyosin receptor kinase (TRK) inhibitors: Design, synthesis, and biological evaluation. European journal of medicinal chemistry. 2021 216:113265. PMID: 33652352.
• Frett B, Saha D, Ryan KR, [et al.]. Pyrazoloadenine Inhibitors of the RET Lung Cancer Oncoprotein Discovered via a Fragment Optimization Approach. ChemMedChem. 2021. PMID: 33559353.
• Wang J, Cheng P, Pavlyukov MS, [et al., including Frett B]. Targeting NEK2 attenuates glioblastoma growth and radioresistance by destabilizing histone methyltransferase EZH2. The Journal of clinical investigation. 2020. PMID: 33044225.
• Lakkaniga NR, Zhang L, Belachew B, [et al., including Frett B]. Discovery of SP-96, the first non-ATP-competitive Aurora Kinase B inhibitor, for reduced myelosuppression. European journal of medicinal chemistry. 2020 203:112589. PMID: 32717530.
• Yan W, Lakkaniga NR, Carlomagno F, [et al., including Frett B]. Correction to Insights into Current Tropomyosin Receptor Kinase (TRK) Inhibitors: Development and Clinical Application. Journal of medicinal chemistry. 2020 63(17):10089. PMID: 32841014.
• Wang J, Cheng P, Pavlyukov MS, [et al., including Frett B]. Targeting NEK2 attenuates glioblastoma growth and radioresistance by destabilizing histone methyltransferase EZH2. The Journal of clinical investigation. 2020 130(9):5027. PMID: 32870163. PMCID: PMC7456217.
• Lakkaniga NR, Gunaganti N, Zhang L, [et al., including Frett B]. Pyrrolo[2,3-d]pyrimidine derivatives as inhibitors of RET: Design, synthesis and biological evaluation. European journal of medicinal chemistry. 2020 206:112691. PMID: 32823007.
• Moccia M, Frett B, Zhang L, [et al.]. Bioisosteric Discovery of NPA101.3, a Second-Generation RET/VEGFR2 Inhibitor Optimized for Single-Agent Polypharmacology. Journal of medicinal chemistry. 2020 63(9):4506-4516. PMID: 32298114.
• Storey AJ, Naceanceno KS, Lan RS, [et al., including Frett B]. ProteoViz: a tool for the analysis and interactive visualization of phosphoproteomics data. Molecular omics. 2020. PMID: 32347222.
• Lei J, Song GT, He LJ, [et al., including Frett B]. Correction: One-pot construction of functionalized aziridines and maleimides via a novel pseudo-Knoevenagel cascade reaction. Chemical communications (Cambridge, England). 2020 56(14):2210. PMID: 32031562.
• Lei J, Song GT, He LJ, [et al., including Frett B]. One-pot construction of functionalized aziridines and maleimides via a novel pseudo-Knoevenagel cascade reaction. Chemical communications (Cambridge, England). 2020 56(14):2194-2197. PMID: 31971170.
• Saha D, Kharbanda A, Yan W, [et al., including Frett B]. The Exploration of Chirality for Improved Druggability within the Human Kinome. Journal of medicinal chemistry. 2020 63(2):441-469. PMID: 31550151.
• Lakkaniga NR, Boerma M, Balasubramaniam M, [et al., including Frett B]. Structural Characterization of the Aurora Kinase B "DFG-flip" Using Metadynamics. The AAPS journal. 2019 22(1):14. PMID: 31853739.
• Yan W, Lakkaniga NR, Carlomagno F, [et al., including Frett B]. Insights into Current Tropomyosin Receptor Kinase (TRK) Inhibitors: Development and Clinical Application. Journal of medicinal chemistry. 2019 62(4):1731-1760. PMID: 30188734.
• Gunaganti N, Kharbanda A, Lakkaniga NR, [et al., including Frett B]. Catalyst free, C-3 functionalization of imidazo[1,2-a]pyridines to rapidly access new chemical space for drug discovery efforts. Chemical communications (Cambridge, England). 2018 54(92):12954-12957. PMID: 30375586. PMCID: PMC6284400.
• Frett B, McConnell N, Kharbanda A, [et al.]. Selective, C-3 Friedel-Crafts acylation to generate functionally diverse, acetylated Imidazo[1,2-a]pyridine derivatives. Tetrahedron. 2018 74(35):4592-4600. PMID: 30344351. PMCID: PMC6192254.
• He LJ, Yang DL, Li SQ, [et al., including Frett B]. Facile construction of fused benzimidazole-isoquinolinones that induce cell-cycle arrest and apoptosis in colorectal cancer cells. Bioorganic & medicinal chemistry. 2018 26(14):3899-3908. PMID: 29921474. PMCID: PMC6718200.
• Lei J, Meng JP, Tang DY, [et al., including Frett B]. Recent advances in the development of polycyclic skeletons via Ugi reaction cascades. Molecular diversity. 2018 22(2):503-516. PMID: 29340996.
• Bharate JB, McConnell N, Naresh G, [et al., including Frett B]. Rational Design, Synthesis and Biological Evaluation of Pyrimidine-4,6-diamine derivatives as Type-II inhibitors of FLT3 Selective Against c-KIT. Scientific reports. 2018 8(1):3722. PMID: 29487300. PMCID: PMC5829162.
• McConnell N, Frett B, Li H. Microwave-assisted green synthesis of anilines, phenols, and benzenediamines without transition metals, ligands, or organic solvents. Green chemistry letters and reviews. 2018 11(3):286-295. PMID: 30984284. PMCID: PMC6457683.
• McConnell N, Xu Z, Kumarasamy V, [et al., including Frett B]. Synthesis of Constrained Heterocycles Employing Two Post-Ugi Cyclization Methods for Rapid Library Generation with In Cellulo Activity. ChemistrySelect. 2017 2(35):11821-11825. PMID: 30140731. PMCID: PMC6103208.
• Wang J, Cheng P, Pavlyukov MS, [et al., including Frett B]. Targeting NEK2 attenuates glioblastoma growth and radioresistance by destabilizing histone methyltransferase EZH2. The Journal of clinical investigation. 2017 127(8):3075-3089. PMID: 28737508. PMCID: PMC5531394.
• Xi JB, Fang YF, Frett B, [et al.]. 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. European journal of medicinal chemistry. 2017 126:1083-1106. PMID: 28039836.
• Fang Y, Frett B, Kong Y, [et al.]. Preclinical activity of MBM-5 in gastrointestinal cancer by inhibiting NEK2 kinase activity. Oncotarget. 2016 7(48):79327-79341. PMID: 27764815. PMCID: PMC5346717.
• Frett B, Carlomagno F, Moccia ML, [et al.]. Fragment-Based Discovery of a Dual pan-RET/VEGFR2 Kinase Inhibitor Optimized for Single-Agent Polypharmacology. Angewandte Chemie (International ed. in English). 2015 54(30):8717-21. PMID: 26126987. PMCID: PMC4535927.