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Brendan Frett

TitleAssistant Professor
InstitutionUniversity of Arkansas for Medical Sciences
DepartmentPharmaceutical Science, College of Pharmacy
DivisionPharmaceutical Science
Address200 South Cedar
Mail Slot # 522
Little Rock AR 72202
Phone501-526-0893
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    Collapse Overview 
    Collapse overview
    Dr. Brendan Frett received his Ph.D. in Pharmaceutical Sciences with an emphasis in Drug Discovery and Development from the University of Arizona in 2014. He received postdoctoral training in Medicinal Chemistry as well as Pharmaceutics at the University of Arizona. Dr. Frett has successfully transferred academic-based discoveries to pharmaceutical companies for clinical development. He is interested in pursuing translational research projects, where research completed in his laboratory can directly help patients.


    Collapse Affiliation 
    Collapse member of
    American Thyroid Association (ATA)

    Collapse Biography 
    Collapse awards and honors
    2018Envoys' Seeds of Science Award, UAMS
    2019Medical Research Endowment Award, UAMS
    2021Rho Chi Pharmacy Honor Society, Honorary Faculty Member, UAMS
    2022Pharmaceutical Sciences Faculty of the Year Award, UAMS

    Collapse Teaching 

    Collapse Research 
    Collapse research activities and funding
    P20GM152281     (MACNICOL, ANGUS)Mar 5, 2024 - Dec 31, 2028
    NIH/Nat. Inst. of General Medical Sciences
    Center for Molecular Interactions in Cancer (CMIC)
    Role: Principal Investigator
    R01CA197178     (LI, HONG-YU)Sep 30, 2015 - Aug 31, 2021
    NIH
    Selective RET Kinase and Its Mutant Inhibitors for the Treatment of Medullary Thyroid Cancer
    Role: Co-Investigator
    P20GM109005     (BOERMA, MARJAN)Jun 24, 2015 - May 31, 2025
    NIH
    Center for Studies of Host Response to Cancer Therapy
    Role: Co-Investigator

    Collapse Bibliographic 
    Collapse selected publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions. Don't see publications published under other names? Login to add alternative names.
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    1. McCrury M, Swafford K, Shuttleworth SL, Mehdi SH, Acharya B, Saha D, Naceanceno K, Byrum SD, Storey AJ, Xu YZ, Doshier C, Patel V, Post GR, De Loose A, Rodriguez A, Shultz LD, Zhan F, Yoon D, Frett B, Kendrick S. Bifunctional Inhibitor Reveals NEK2 as a Therapeutic Target and Regulator of Oncogenic Pathways in Lymphoma. Mol Cancer Ther. 2024 Mar 04; 23(3):316-329. PMID: 37816504.
      View in: PubMed
    2. Frett B, Stephens KE, Koss B, Melnyk S, Farrar J, Saha D, Roy Choudhury S. Enhancer-activated RET confers protection against oxidative stress to KMT2A-rearranged acute myeloid leukemia. Cancer Sci. 2024 Mar; 115(3):963-973. PMID: 38226414.
      View in: PubMed
    3. Acharya B, Saha D, Armstrong D, Jabali B, Hanafi M, Herrera-Rueda A, Lakkaniga NR, Frett B. Kinase inhibitor macrocycles: a perspective on limiting conformational flexibility when targeting the kinome with small molecules. RSC Med Chem. 2024 Feb 21; 15(2):399-415. PMID: 38389874.
      View in: PubMed
    4. Acharya B, Frett B. An updated patent review of rearranged during transfection (RET) kinase inhibitors (2016-present). Expert Opin Ther Pat. 2022 Oct; 32(10):1067-1077. PMID: 36198171.
      View in: PubMed
    5. Swafford K, Acharya B, Xu YZ, Raney T, McCrury M, Saha D, Frett B, Kendrick S. Targeting a Novel G-Quadruplex in the CARD11 Oncogene Promoter with Naptho(2,1-b)furan-1-ethanol,2-nitro- Requires the Nitro Group. Genes (Basel). 2022 06 25; 13(7). PMID: 35885931.
      View in: PubMed
    6. Acharya B, Saha D, Armstrong D, Lakkaniga NR, Frett B. FLT3 inhibitors for acute myeloid leukemia: successes, defeats, and emerging paradigms. RSC Med Chem. 2022 Jul 20; 13(7):798-816. PMID: 35923716.
      View in: PubMed
    7. Acharya B, Miah S, Frett B. Targeting TGF-?: triumphs and challenges. Future Med Chem. 2022 04; 14(7):455-458. PMID: 35152715.
      View in: PubMed
    8. Zhang L, Moccia M, Briggs DC, Bharate JB, Lakkaniga NR, Knowles P, Yan W, Tran P, Kharbanda A, Wang X, Leung YK, Frett B, Santoro M, McDonald NQ, Carlomagno F, Li HY. Discovery of N-Trisubstituted Pyrimidine Derivatives as Type I RET and RET Gatekeeper Mutant Inhibitors with a Novel Kinase Binding Pose. J Med Chem. 2022 01 27; 65(2):1536-1551. PMID: 35081714.
      View in: PubMed
    9. Saha D, Ryan KR, Lakkaniga NR, Acharya B, Garcia NG, Smith EL, Frett B. Targeting Rearranged during Transfection in Cancer: A Perspective on Small-Molecule Inhibitors and Their Clinical Development. J Med Chem. 2021 08 26; 64(16):11747-11773. PMID: 34402300.
      View in: PubMed
    10. Zhang L, Lakkaniga NR, Bharate JB, Mcconnell N, Wang X, Kharbanda A, Leung YK, Frett B, Shah NP, Li HY. 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. Eur J Med Chem. 2021 Dec 05; 225:113776. PMID: 34479037.
      View in: PubMed
    11. Kharbanda A, Tran P, Zhang L, Leung YK, Li HY, Frett B. Discovery of 4-aminoquinolines as highly selective TGF?R1 inhibitors with an attenuated MAP4K4 profile for potential applications in immuno-oncology. Eur J Med Chem. 2021 Dec 05; 225:113763. PMID: 34419892.
      View in: PubMed
    12. Moccia M, Yang D, Lakkaniga NR, Frett B, McConnell N, Zhang L, Brescia A, Federico G, Zhang L, Salerno P, Santoro M, Li HY, Carlomagno F. Targeted activity of the small molecule kinase inhibitor Pz-1 towards RET and TRK kinases. Sci Rep. 2021 08 09; 11(1):16103. PMID: 34373541.
      View in: PubMed
    13. Kharbanda A, Zhang L, Saha D, Tran P, Xu K, Li MO, Leung YK, Frett B, Li HY. Discovery and biological evaluation of phthalazines as novel non-kinase TGF? pathway inhibitors. Eur J Med Chem. 2021 Nov 05; 223:113660. PMID: 34246853.
      View in: PubMed
    14. Saha D, Ryan KR, Lakkaniga NR, Smith EL, Frett B. Pyrazoloadenine Inhibitors of the RET Lung Cancer Oncoprotein Discovered by a Fragment Optimization Approach. ChemMedChem. 2021 05 18; 16(10):1605-1608. PMID: 33559353.
      View in: PubMed
    15. Yan W, Zhang L, Lv F, Moccia M, Carlomagno F, Landry C, Santoro M, Gosselet F, Frett B, Li HY. Discovery of pyrazolo-thieno[3,2-d]pyrimidinylamino-phenyl acetamides as type-II pan-tropomyosin receptor kinase (TRK) inhibitors: Design, synthesis, and biological evaluation. Eur J Med Chem. 2021 Apr 15; 216:113265. PMID: 33652352.
      View in: PubMed
    16. Wang J, Cheng P, Pavlyukov MS, Yu H, Zhang Z, Kim SH, Minata M, Mohyeldin A, Xie W, Chen D, Goidts V, Frett B, Hu W, Li H, Shin YJ, Lee Y, Nam DH, Kornblum HI, Wang M, Nakano I. Targeting NEK2 attenuates glioblastoma growth and radioresistance by destabilizing histone methyltransferase EZH2. J Clin Invest. 2020 11 02; 130(11):6187. PMID: 33044225.
      View in: PubMed
    17. Wang J, Cheng P, Pavlyukov MS, Yu H, Zhang Z, Kim SH, Minata M, Mohyeldin A, Xie W, Chen D, Goidts V, Frett B, Hu W, Li H, Shin YJ, Lee Y, Nam DH, Kornblum HI, Wang M, Nakano I. Targeting NEK2 attenuates glioblastoma growth and radioresistance by destabilizing histone methyltransferase EZH2. J Clin Invest. 2020 09 01; 130(9):5027. PMID: 32870163.
      View in: PubMed
    18. Yan W, Lakkaniga NR, Carlomagno F, Santoro M, McDonald NQ, Lv F, Gunaganti N, Frett B, Li HY. Correction to Insights into Current Tropomyosin Receptor Kinase (TRK) Inhibitors: Development and Clinical Application. J Med Chem. 2020 Sep 10; 63(17):10089. PMID: 32841014.
      View in: PubMed
    19. Lakkaniga NR, Gunaganti N, Zhang L, Belachew B, Frett B, Leung YK, Li HY. Pyrrolo[2,3-d]pyrimidine derivatives as inhibitors of RET: Design, synthesis and biological evaluation. Eur J Med Chem. 2020 Nov 15; 206:112691. PMID: 32823007.
      View in: PubMed
    20. Lakkaniga NR, Zhang L, Belachew B, Gunaganti N, Frett B, Li HY. Discovery of SP-96, the first non-ATP-competitive Aurora Kinase B inhibitor, for reduced myelosuppression. Eur J Med Chem. 2020 Oct 01; 203:112589. PMID: 32717530.
      View in: PubMed
    21. Storey AJ, Naceanceno KS, Lan RS, Washam CL, Orr LM, Mackintosh SG, Tackett AJ, Edmondson RD, Wang Z, Li HY, Frett B, Kendrick S, Byrum SD. ProteoViz: a tool for the analysis and interactive visualization of phosphoproteomics data. Mol Omics. 2020 08 01; 16(4):316-326. PMID: 32347222.
      View in: PubMed
    22. Moccia M, Frett B, Zhang L, Lakkaniga NR, Briggs DC, Chauhan R, Brescia A, Federico G, Yan W, Santoro M, McDonald NQ, Li HY, Carlomagno F. Bioisosteric Discovery of NPA101.3, a Second-Generation RET/VEGFR2 Inhibitor Optimized for Single-Agent Polypharmacology. J Med Chem. 2020 05 14; 63(9):4506-4516. PMID: 32298114.
      View in: PubMed
    23. Lei J, Song GT, He LJ, Luo YF, Tang DY, Lin HK, Frett B, Li HY, Chen ZZ, Xu ZG. Correction: One-pot construction of functionalized aziridines and maleimides via a novel pseudo-Knoevenagel cascade reaction. Chem Commun (Camb). 2020 Feb 18; 56(14):2210. PMID: 32031562.
      View in: PubMed
    24. Lei J, Song GT, He LJ, Luo YF, Tang DY, Lin HK, Frett B, Li HY, Chen ZZ, Xu ZG. One-pot construction of functionalized aziridines and maleimides via a novel pseudo-Knoevenagel cascade reaction. Chem Commun (Camb). 2020 Feb 18; 56(14):2194-2197. PMID: 31971170.
      View in: PubMed
    25. Lakkaniga NR, Balasubramaniam M, Zhang S, Frett B, Li HY. Structural Characterization of the Aurora Kinase B "DFG-flip" Using Metadynamics. AAPS J. 2019 12 18; 22(1):14. PMID: 31853739.
      View in: PubMed
    26. Saha D, Kharbanda A, Yan W, Lakkaniga NR, Frett B, Li HY. The Exploration of Chirality for Improved Druggability within the Human Kinome. J Med Chem. 2020 01 23; 63(2):441-469. PMID: 31550151.
      View in: PubMed
    27. Gunaganti N, Kharbanda A, Lakkaniga NR, Zhang L, Cooper R, Li HY, Frett B. Catalyst free, C-3 functionalization of imidazo[1,2-a]pyridines to rapidly access new chemical space for drug discovery efforts. Chem Commun (Camb). 2018 Nov 15; 54(92):12954-12957. PMID: 30375586.
      View in: PubMed
    28. Yan W, Lakkaniga NR, Carlomagno F, Santoro M, McDonald NQ, Lv F, Gunaganti N, Frett B, Li HY. Insights into Current Tropomyosin Receptor Kinase (TRK) Inhibitors: Development and Clinical Application. J Med Chem. 2019 02 28; 62(4):1731-1760. PMID: 30188734.
      View in: PubMed
    29. Frett B, McConnell N, Kharbanda A, Naresh G, Rounseville B, Warner C, Chang J, Debolske N, Li HY. Selective, C-3 Friedel-Crafts acylation to generate functionally diverse, acetylated Imidazo[1,2-a]pyridine derivatives. Tetrahedron. 2018 Aug 30; 74(35):4592-4600. PMID: 30344351.
      View in: PubMed
    30. McConnell N, Frett B, Li H. Microwave-assisted green synthesis of anilines, phenols, and benzenediamines without transition metals, ligands, or organic solvents. Green Chem Lett Rev. 2018; 11(3):286-295. PMID: 30984284.
      View in: PubMed
    31. He LJ, Yang DL, Li SQ, Zhang YJ, Tang Y, Lei J, Frett B, Lin HK, Li HY, Chen ZZ, Xu ZG. Facile construction of fused benzimidazole-isoquinolinones that induce cell-cycle arrest and apoptosis in colorectal cancer cells. Bioorg Med Chem. 2018 08 07; 26(14):3899-3908. PMID: 29921474.
      View in: PubMed
    32. Bharate JB, McConnell N, Naresh G, Zhang L, Lakkaniga NR, Ding L, Shah NP, Frett B, Li HY. Rational Design, Synthesis and Biological Evaluation of Pyrimidine-4,6-diamine derivatives as Type-II inhibitors of FLT3 Selective Against c-KIT. Sci Rep. 2018 02 27; 8(1):3722. PMID: 29487300.
      View in: PubMed
    33. Lei J, Meng JP, Tang DY, Frett B, Chen ZZ, Xu ZG. Recent advances in the development of polycyclic skeletons via Ugi reaction cascades. Mol Divers. 2018 May; 22(2):503-516. PMID: 29340996.
      View in: PubMed
    34. McConnell N, Xu Z, Kumarasamy V, Sun D, Frett B, Li HY. Synthesis of Constrained Heterocycles Employing Two Post-Ugi Cyclization Methods for Rapid Library Generation with In Cellulo Activity. ChemistrySelect. 2017 12 11; 2(35):11821-11825. PMID: 30140731.
      View in: PubMed
    35. Wang J, Cheng P, Pavlyukov MS, Yu H, Zhang Z, Kim SH, Minata M, Mohyeldin A, Xie W, Chen D, Goidts V, Frett B, Hu W, Li H, Shin YJ, Lee Y, Nam DH, Kornblum HI, Wang M, Nakano I. Targeting NEK2 attenuates glioblastoma growth and radioresistance by destabilizing histone methyltransferase EZH2. J Clin Invest. 2017 Aug 01; 127(8):3075-3089. PMID: 28737508.
      View in: PubMed
    36. Xi JB, Fang YF, Frett B, Zhu ML, Zhu T, Kong YN, Guan FJ, Zhao Y, Zhang XW, Li HY, Ma ML, 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 Jan 27; 126:1083-1106. PMID: 28039836.
      View in: PubMed
    37. Frett B, Carlomagno F, Moccia ML, Brescia A, Federico G, De Falco V, Admire B, Chen Z, Qi W, Santoro M, Li HY. Fragment-Based Discovery of a Dual pan-RET/VEGFR2 Kinase Inhibitor Optimized for Single-Agent Polypharmacology. Angew Chem Int Ed Engl. 2015 Jul 20; 54(30):8717-21. PMID: 26126987.
      View in: PubMed
    38. Wang Y, Frett B, McConnell N, Li HY. Metal-free, efficient hydrazination of imidazo[1,2-a]pyridine with diethyl azodicarboxylate in neutral media. Org Biomol Chem. 2015 Mar 14; 13(10):2958-64. PMID: 25611884.
      View in: PubMed
    39. Frett B, McConnell N, Smith CC, Wang Y, Shah NP, Li HY. Computer aided drug discovery of highly ligand efficient, low molecular weight imidazopyridine analogs as FLT3 inhibitors. Eur J Med Chem. 2015 Apr 13; 94:123-31. PMID: 25765758.
      View in: PubMed
    40. Frett B, Moccia M, Carlomagno F, Santoro M, Li HY. Identification of two novel RET kinase inhibitors through MCR-based drug discovery: design, synthesis and evaluation. Eur J Med Chem. 2014 Oct 30; 86:714-23. PMID: 25232968.
      View in: PubMed
    41. Frett B, McConnell N, Wang Y, Xu Z, Ambrose A, Li HY. Identification of pyrazine-based TrkA inhibitors: design, synthesis, evaluation, and computational modeling studies. Medchemcomm. 2014 Oct 01; 5(10):1507-1514. PMID: 26843921.
      View in: PubMed
    42. Li F, Frett B, Li HY. Selective Reduction of Halogenated Nitroarenes with Hydrazine Hydrate in the Presence of Pd/C. Synlett. 2014 Jun; 25(10):1403-1408. PMID: 26843785.
      View in: PubMed
    43. Wang Y, Frett B, Li HY. Efficient access to 2,3-diarylimidazo[1,2-a]pyridines via a one-pot, ligand-free, palladium-catalyzed three-component reaction under microwave irradiation. Org Lett. 2014 Jun 06; 16(11):3016-9. PMID: 24854606.
      View in: PubMed
    44. Frett B, Brown RV, Ma M, Hu W, Han H, Li HY. Therapeutic melting pot of never in mitosis gene a related kinase 2 (Nek2): a perspective on Nek2 as an oncology target and recent advancements in Nek2 small molecule inhibition. J Med Chem. 2014 Jul 24; 57(14):5835-44. PMID: 24517277.
      View in: PubMed
    45. Frett B, Wang Y, Li HY. Targeting the K-Ras/PDEd protein-protein interaction: the solution for Ras-driven cancers or just another therapeutic mirage? ChemMedChem. 2013 Oct; 8(10):1620-2. PMID: 23939923.
      View in: PubMed
    46. Roberts SA, Saha B, Frett B, Li HY. (Z)-N-tert-Butyl-2-(4-meth-oxy-anilino)-N'-(4-meth-oxy-phen-yl)-2-phenyl-acetimidamide. Acta Crystallogr Sect E Struct Rep Online. 2013 Jun 01; 69(Pt 6):o902. PMID: 23795077.
      View in: PubMed
    47. Wang Y, Kaiser CE, Frett B, Li HY. Targeting mutant KRAS for anticancer therapeutics: a review of novel small molecule modulators. J Med Chem. 2013 Jul 11; 56(13):5219-30. PMID: 23566315.
      View in: PubMed
    48. Gunawan S, Ayaz M, De Moliner F, Frett B, Kaiser C, Patrick N, Xu Z, Hulme C. Synthesis of Tetrazolo-Fused Benzodiazepines and Benzodiazepinones by a Two-Step Protocol Using an Ugi-Azide Reaction for Initial Diversity Generation. Tetrahedron. 2012 Jul 08; 68(27-28):5606-5611. PMID: 22923851.
      View in: PubMed
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