Brendan Andrew Frett, PhD

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

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 – 1P20GM152281
  “Center for Molecular Interactions in Cancer (CMIC)”
  Co-Investigator
  3/5/2024 – 12/31/2028
• NIH/Nat. Inst. of General Medical Sciences – 2P20GM109005
  “Concurrent Tnf-Alpha and Tgf-Beta Impairment To Limit Radiotherapy-Induced Pulmonary Fibrosis”
  Principal Investigator
  8/17/2020 – 5/31/2025

Recent Publications

• Waldrip ZJ, Acharya B, Armstrong D, [et al., including Frett B]. Discovery of the DNA-PKcs inhibitor DA-143 which exhibits enhanced solubility relative to NU7441. Scientific reports. 2024 14(1):19999. PMID: 39198533. PMCID: PMC11358143.
• Acharya B, Saha D, Garcia Garcia N, [et al., including Frett B]. Discovery of 9H-pyrimido[4,5-b]indole derivatives as dual RET/TRKA inhibitors. Bioorganic & medicinal chemistry. 2024 106:117749. PMID: 38744018. PMCID: PMC11144469.
• Acharya B, Saha D, Armstrong D, [et al., including Frett B]. Kinase inhibitor macrocycles: a perspective on limiting conformational flexibility when targeting the kinome with small molecules. RSC medicinal chemistry. 2024 15(2):399-415. PMID: 38389874. PMCID: PMC10880908.
• Frett B, Stephens KE, Koss B, [et al.]. Enhancer-activated RET confers protection against oxidative stress to KMT2A-rearranged acute myeloid leukemia. Cancer science. 2024. PMID: 38226414. PMCID: PMC10920984.
• McCrury M, Swafford K, Shuttleworth SL, [et al., including Frett B]. Bifunctional inhibitor reveals NEK2 as a therapeutic target and regulator of oncogenic pathways in lymphoma. Molecular cancer therapeutics. 2023. PMID: 37816504. PMCID: PMC10932871.
• Acharya B, Frett B. An updated patent review of rearranged during transfection (RET) kinase inhibitors (2016-present). Expert opinion on therapeutic patents. 2022 32(10):1067-1077. PMID: 36198171.
• Acharya B, Saha D, Armstrong D, [et al., including Frett B]. FLT3 inhibitors for acute myeloid leukemia: successes, defeats, and emerging paradigms. RSC medicinal chemistry. 2022 13(7):798-816. PMID: 35923716. PMCID: PMC9298189.
• Swafford K, Acharya B, Xu YZ, [et al., including Frett B]. 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. 2022 13(7). PMID: 35885931. PMCID: PMC9321325.
• Acharya B, Miah S, Frett B. Targeting TGF-β: 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. PMCID: PMC10536133.
• 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. PMCID: PMC9697126.
• 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. PMCID: PMC8585723.
• Kharbanda A, Tran P, Zhang L, [et al., including Frett B]. Discovery of 4-aminoquinolines as highly selective TGFβR1 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 TGFβ pathway inhibitors. European journal of medicinal chemistry. 2021 223:113660. PMID: 34246853. PMCID: PMC9472513.
• 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 by a Fragment Optimization Approach. ChemMedChem. 2021. PMID: 33559353. PMCID: PMC9969764.
• 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. PMCID: PMC7598038.
• 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. PMCID: PMC10536156.
• 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. PMCID: PMC7901654.
• 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. PMCID: PMC7423749.
• 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.
• 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.
• 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. PMCID: PMC10536157.
• 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. PMCID: PMC7905835.