Thomas Bannister

Thomas Bannister, Ph.D.

Research Professor (Sr. Scientific Director), Department Of Molecular Medicine

Department: SR-MM-BANNISTER LAB
Business Phone: (561) 228-2206
Business Email: t.bannister@ufl.edu

About Thomas Bannister

Related Links:
Additional Positions:
Core Director, Medicinal Chemistry Support
2022 – Current · Midwest AviDD (Antivial Drug Discovery) Center
ACS MEDI Division Chair (elected)
2014 – 2016 · Medicinal Chemistry Division of the American Chemical Society
ACS MEDI Long-range planning committee
2014 – 2016 · Medicinal Chemistry Division of the American Chemical Society
ACS MEDI Long-range planning committee
2009 – 2011 · medicinal Chemistry Division of the American Chemical Society
Chemstry Department Faculty
2005 – 2018 · Scripps Florida

Teaching Profile

Teaching Philosophy
I contribute lectures on medicinal chemistry to a Scripps graduate course offered in alternate years on Principles of Drug Discovery (TRBIO 450).

Research Profile

Organic/Medicinal Chemistry and Drug Discovery

The discovery of possible drug candidates is a highly collaborative endeavor, with medicinal chemistry as a core, problem-solving component. My major research efforts are joint projects with world experts in cancer biology and neuroscience, wherein my group provides the organic and medicinal chemistry expertise and drug design insights. In general, we strive to find novel ways to target poorly-treated, common, and devastating disorders that increasingly burden world health care systems.

Neuroscience studies include:

— Biased mu opioid agonists, aiming for a holy grail of sorts: to separate the robust pain relief –provided by opiates from their many unwanted side effects. This collaboration with Laura Bohn’s group has led to findings published in 2017 in Cell, with follow-up chemistry disclosure in the Journal of Medicinal Chemistry in late 2018 (featured on the cover). — NOP agonists, for post-traumatic stress disorder (PTSD) and alcohol addiction relapse therapy. — NAD-elevating neuroprotectants, for Alzheimer’s and Parkinson’s Diseases, and for ALS.

Cancer projects include:

— KLF5 inhibitors for colorectal cancer therapy. — TBK1 and IKKi dual kinase inhibitors, for hormone-refractory prostate cancer. — Inhibitors of kinases CK1delta, ASK1, and ULK1, for various cancers. — Modulators of the HIPPO-YAP pathway, for various cancers. — Other exploratory efforts include:

High-throughput screening-based “chemical probe development”, seeking first-in-class small molecules for investigating the therapeutic potential of new target proteins. Probe development efforts encompass multiple therapeutic areas, including treatments for cancers, glaucoma, amyotrophic lateral sclerosis (ALS), Alzheimer’s disease (AD), addiction, infectious diseases, and mood disorders. One chemical probe effort targets the orphan GPCR GPR151, a target that may be relevant for the development of treatments for addiction, depression, and schizophrenia.The discovery of possible drug candidates is a highly collaborative endeavor, with medicinal chemistry as a core, problem-solving component. Our major efforts are thus joint projects with world experts in cancer biology and neuroscience, wherein our group provides the organic and medicinal chemistry expertise.

Our cancer projects target unique metabolic phenotypes of tumor cells, identifying defining molecular characteristics to be exploited for the development of targeted therapies. Most tumor types have a shared reliance upon active transport of nutrients and building blocks to drive rapid cancer cell growth and to sustain survival. They also largely rely upon glycolysis for ATP production (the Warburg effect). As examples, we have created molecules to keep tumor cells from exporting lactate, the end product of glycolysis. We have also designed compounds to block amino acid transporters that are up-regulated by many tumors. We have a program targeting expression of a transcription factor that drives colon cancer progression. We also have a number of kinase inhibitor programs aimed the discovery of treatments for brain cancers, triple-negative breast cancer, hormone-resistant prostate cancer, and perhaps other forms as well. This are collaborative efforts with top TSRI cancer biologists including Derek Duckett, Joseph Kissil, Jun-li Luo, and also including John Cleveland from the Moffitt Cancer Center.

Many of our anticancer programs have a computational chemistry-directed focus, relying on molecular modeling based upon published coordinates, virtual screening, scoring, and validation of predicted hits through chemical synthesis. We use the Schrodinger suite of modeling software in these studies. For future work we may have a need to hire postdoctoral scientists with both computational and synthesis experience. Please contact me for further information.

In our neuroscience studies we are developing GPCR agonists that have targeted effects in the brain. We are exploring GPCR signaling bias in mu opioid receptor activation, aiming for a holy grail of sorts: to separate the robust pain relief provided by opiates from their many unwanted side effects. This collaboration with Laura Bohn’s group has led to pain relievers that seem to be devoid of many of the side effects of morphine and related opiates, such as respiratory suppression, heart rate effects, and GI effects (constipation). In a separate study we identified tool compound with promise in an animal model of post-traumatic stress disorder (PTSD).

Other exploratory efforts use medicinal chemistry in concert with high-throughput screening or following HTS campaigns, where we seek to discover and optimize “chemical probes”, or first-in-class small molecules that should prove useful for investigating the therapeutic potential of new target proteins. Such probe development efforts encompass multiple therapeutic areas, including treatments for ALS, Parkinson’s Disease, addiction, infectious diseases, cancers, glaucoma, and mood disorders.

One such chemical probe effort, a collaboration with Patsy McDonald, targets the orphan GPCR GPR151, a target that may be relevant for the development of treatments for addiction, depression, and schizophrenia. In a collaboration with Sathya Puthanveettil we are investigating the potential of facilitating the function of kinesin motor proteins as a novel approach to therapies for Alzheimer’s disease (AD) and frontal temporal dementia (FTD), which are poorly-treated, common, and devastating disorders that increasingly burden world health care systems. In a collaboration with Corinne Lasmezas, we are developing compounds that rescue neurons from toxicity of protein aggregates, relevant for developing new therapies for ALS and Parkinson’s Disease.

As you can tell, collaborative drug discovery research is order of the day in my lab!

Members of my group benefit from interactions not only with other chemists but with top biologists and pharmacologists, as they partake in project team meetings as well as in our weekly chemistry group meetings. My research is funded currently by 8 NIH grants on which I am a co-principal investigator and 8 others NIH grants where I am a named investigator or co-investigator.

On occasion I have openings for outstanding postdoctoral fellows in my labs. As mentioned above, an especially good fit would be a postdoc with lab synthesis experience and with prior expertise in using the Schrodinger suite of molecular modeling software, to aid our virtual screening-based efforts. Our postdoctoral scientists collaborate with a team of biological co-investigators, applying knowledge and experience in modern organic, heterocyclic, and/or medicinal chemistry toward an ongoing drug discovery effort. Excellent communication skills, good synthetic organic chemistry laboratory skills, ability to work in the US, and familiarity with modern synthetic techniques and instrumentation are required in this role. Contact me for further details.

Open Researcher and Contributor ID (ORCID)

0000-0003-0683-8886

Publications

2022
Identification of potent small molecule inhibitors of SARS-CoV-2 entry.
SLAS discovery : advancing life sciences R & D. [DOI] 10.1016/j.slasd.2021.10.012. [PMID] 35058179.
2021
Comparison of morphine, oxycodone and the biased MOR agonist SR-17018 for tolerance and efficacy in mouse models of pain.
Neuropharmacology. [DOI] 10.1016/j.neuropharm.2020.108439. [PMID] 33345829.
2021
Discovery and Optimization of Selective Inhibitors of Meprin α (Part I).
Pharmaceuticals (Basel, Switzerland). [DOI] 10.3390/ph14030203. [PMID] 33671080.
2021
Discovery and Optimization of Selective Inhibitors of Meprin α (Part II).
Pharmaceuticals (Basel, Switzerland). [DOI] 10.3390/ph14030197. [PMID] 33673639.
2021
G protein signaling–biased mu opioid receptor agonists that produce sustained G protein activation are noncompetitive agonists
Proceedings of the National Academy of Sciences. [DOI] 10.1073/pnas.2102178118. [PMID] 34819362.
2021
Identification of Potential Modulators of the RGS7/Gβ5/R7BP Complex.
SLAS discovery : advancing life sciences R & D. [DOI] 10.1177/24725552211020679. [PMID] 34112017.
2021
Identification of Small-Molecule Inhibitors of Neutral Ceramidase (nCDase) via Target-Based High-Throughput Screening.
SLAS discovery : advancing life sciences R & D. [DOI] 10.1177/2472555220945283. [PMID] 32734807.
2020
A G protein signaling-biased agonist at the μ-opioid receptor reverses morphine tolerance while preventing morphine withdrawal.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. [DOI] 10.1038/s41386-019-0491-8. [PMID] 31443104.
2020
Oregano Oil and Its Principal Component, Carvacrol, Inhibit HIV-1 Fusion into Target Cells.
Journal of virology. [DOI] 10.1128/JVI.00147-20. [PMID] 32461309.
2020
Rescue of mutant gonadotropin-releasing hormone receptor function independent of cognate receptor activity.
Scientific reports. [DOI] 10.1038/s41598-020-67473-w. [PMID] 32601341.
2019
Native Directed Site-Selective δ-C(sp3)–H and δ-C(sp2)–H Arylation of Primary Amines
ACS Catalysis. [DOI] 10.1021/acscatal.8b04927.
2018
A Rapid Phenotypic Whole-Cell Screening Approach for the Identification of Small-Molecule Inhibitors That Counter β-Lactamase Resistance in Pseudomonas aeruginosa.
SLAS discovery : advancing life sciences R & D. [DOI] 10.1177/2472555217728489. [PMID] 28850797.
2018
Chemical validation and optimization of pharmacoperones targeting vasopressin type 2 receptor mutant.
The Biochemical journal. [DOI] 10.1042/BCJ20180065. [PMID] 30068530.
2018
Identification of Novel, Structurally Diverse, Small Molecule Modulators of GPR119.
Assay and drug development technologies. [DOI] 10.1089/adt.2018.849. [PMID] 30019946.
2018
Optimization of a Series of Mu Opioid Receptor (MOR) Agonists with High G Protein Signaling Bias
Journal of Medicinal Chemistry. [DOI] 10.1021/acs.jmedchem.8b01136. [PMID] 30199635.
2018
Site-Selective γ-C(sp3 )-H and γ-C(sp2 )-H Arylation of Free Amino Esters Promoted by a Catalytic Transient Directing Group.
Chemistry (Weinheim an der Bergstrasse, Germany). [DOI] 10.1002/chem.201802465. [PMID] 29775502.
2017
Bias Factor and Therapeutic Window Correlate to Predict Safer Opioid Analgesics.
Cell. [DOI] 10.1016/j.cell.2017.10.035. [PMID] 29149605.
2017
Pharmacoperone rescue of vasopressin 2 receptor mutants reveals unexpected constitutive activity and coupling bias.
PloS one. [DOI] 10.1371/journal.pone.0181830. [PMID] 28767678.
2016
Discovery of an enzyme and substrate selective inhibitor of ADAM10 using an exosite-binding glycosylated substrate.
Scientific reports. [DOI] 10.1038/s41598-016-0013-4. [PMID] 28442704.
2016
Exploiting the co-reliance of tumours upon transport of amino acids and lactate: Gln and Tyr conjugates of MCT1 inhibitors.
MedChemComm. [PMID] 27347360.
2016
Identification of Potential Pharmacoperones Capable of Rescuing the Functionality of Misfolded Vasopressin 2 Receptor Involved in Nephrogenic Diabetes Insipidus.
Journal of biomolecular screening. [DOI] 10.1177/1087057116653925. [PMID] 27280550.
2016
ML264, A Novel Small-Molecule Compound That Potently Inhibits Growth of Colorectal Cancer.
Molecular cancer therapeutics. [DOI] 10.1158/1535-7163.MCT-15-0600. [PMID] 26621868.
2016
Receptor antagonism/agonism can be uncoupled from pharmacoperone activity.
Molecular and cellular endocrinology. [DOI] 10.1016/j.mce.2016.07.003. [PMID] 27389877.
2016
Synthesis and Cytoxicity of Sempervirine and Analogues.
The Journal of organic chemistry. [DOI] 10.1021/acs.joc.6b00022. [PMID] 26828413.
2015
Identification of potent inhibitors of the Trypanosoma brucei methionyl-tRNA synthetase via high-throughput orthogonal screening.
Journal of biomolecular screening. [DOI] 10.1177/1087057114548832. [PMID] 25163684.
2015
Identification of small molecules that disrupt signaling between ABL and its positive regulator RIN1.
PloS one. [DOI] 10.1371/journal.pone.0121833. [PMID] 25811598.
2015
One-pot directed alkylation/deprotection strategy for the synthesis of substituted pyrrole[3,4-d]pyridazinones.
European journal of organic chemistry. [PMID] 26257580.
2015
Preparation of tetrasubstituted pyrimido[4,5-d]pyrimidine diones.
Tetrahedron letters. [PMID] 27087706.
2015
Selective Targeting of Extracellular Insulin-Degrading Enzyme by Quasi-Irreversible Thiol-Modifying Inhibitors.
ACS chemical biology. [DOI] 10.1021/acschembio.5b00334. [PMID] 26398879.
2014
Blocking lactate export by inhibiting the Myc target MCT1 Disables glycolysis and glutathione synthesis.
Cancer research. [DOI] 10.1158/0008-5472.CAN-13-2034. [PMID] 24285728.
2014
Grubbs cross-metathesis pathway for a scalable synthesis of γ-keto-α,β-unsaturated esters.
The Journal of organic chemistry. [DOI] 10.1021/jo4023606. [PMID] 24393145.
2014
Sequential Sonagashira and Larock indole synthesis reactions in a general strategy to prepare biologically active β-carboline-containing alkaloids.
Organic letters. [DOI] 10.1021/ol5029783. [PMID] 25393979.
2014
Synthesis and structure-activity relationships of pteridine dione and trione monocarboxylate transporter 1 inhibitors.
Journal of medicinal chemistry. [DOI] 10.1021/jm500640x. [PMID] 25068893.
2013
Amino acid derived quinazolines as Rock/PKA inhibitors.
Bioorganic & medicinal chemistry letters. [DOI] 10.1016/j.bmcl.2013.01.109. [PMID] 23416002.
2013
Amygdala-dependent fear is regulated by Oprl1 in mice and humans with PTSD.
Science translational medicine. [DOI] 10.1126/scitranslmed.3005656. [PMID] 23740899.
2013
Hydroxyquinoline-derived compounds and analoguing of selective Mcl-1 inhibitors using a functional biomarker.
Bioorganic & medicinal chemistry. [DOI] 10.1016/j.bmc.2013.08.017. [PMID] 23993674.
2012
Small-molecule inhibitors of bacterial AddAB and RecBCD helicase-nuclease DNA repair enzymes.
ACS chemical biology. [DOI] 10.1021/cb300018x. [PMID] 22443934.
2011
Discovery and optimization of indole and 7-azaindoles as Rho kinase (ROCK) inhibitors (part-II).
Bioorganic & medicinal chemistry letters. [DOI] 10.1016/j.bmcl.2011.09.084. [PMID] 22018789.
2011
Discovery and optimization of indoles and 7-azaindoles as Rho kinase (ROCK) inhibitors (part-I).
Bioorganic & medicinal chemistry letters. [DOI] 10.1016/j.bmcl.2011.09.083. [PMID] 22004718.
2011
Identification of small-molecule inhibitors of the colorectal cancer oncogene Krüppel-like factor 5 expression by ultrahigh-throughput screening.
Molecular cancer therapeutics. [DOI] 10.1158/1535-7163.MCT-11-0550. [PMID] 21885866.
2011
Synthesis and biological evaluation of 4-quinazolinones as Rho kinase inhibitors.
Bioorganic & medicinal chemistry letters. [DOI] 10.1016/j.bmcl.2011.01.039. [PMID] 21349713.
2010
The development of benzimidazoles as selective rho kinase inhibitors.
Bioorganic & medicinal chemistry letters. [DOI] 10.1016/j.bmcl.2010.01.124. [PMID] 20167489.
2008
Benzimidazole- and benzoxazole-based inhibitors of Rho kinase.
Bioorganic & medicinal chemistry letters. [DOI] 10.1016/j.bmcl.2008.10.095. [PMID] 18996009.
2008
Chroman-3-amides as potent Rho kinase inhibitors.
Bioorganic & medicinal chemistry letters. [DOI] 10.1016/j.bmcl.2008.10.080. [PMID] 18990570.
2006
Design, synthesis, and biological evaluation of peptidomimetic inhibitors of factor XIa as novel anticoagulants.
Journal of medicinal chemistry. [PMID] 17181160.
1975
In vitro activity of tobramycin and gentamicin against Enterobacteriaceae and gentamicin-resistant, carbenicillin-resistant Pseudomonas aeruginosa.
Current therapeutic research, clinical and experimental. [PMID] 805033.
1974
Comparison of the in vitro activity of BL-P1654 with gentamicin and carbenicillin against Pseudomonas aeruginosa.
Antimicrobial agents and chemotherapy. [PMID] 4157347.
1969
In vitro susceptibility of Pseudomonas aeruginosa to carbenicillin and the combination of carbenicillin and gentamicin.
Applied microbiology. [PMID] 4984762.

Grants

Apr 2022 ACTIVE
Identification of novel anthelmintics through a target-based screen of a parasite ion channel
Role: Co-Investigator
Funding: MEDICAL COLLEGE OF WISCONSIN via NATL INST OF HLTH NIAID
Apr 2022 ACTIVE
Development of New Casein Kinase 1 Inhibitor for the Treatment of Brain Cancers
Role: Principal Investigator
Funding: H LEE MOFFITT CANCER CTR via NATL INST OF HLTH NCI
Apr 2022 ACTIVE
Synthesis and Evaluation of Functionally Biased Opioid Analgesics
Role: Principal Investigator
Funding: NATL INST OF HLTH NIDA
Apr 2022 ACTIVE
Therapeutic Targeting of Casein Kinase-1-delta in Primary Metastatic Breast Cancer
Role: Principal Investigator
Funding: H LEE MOFFITT CANCER CTR via NATL INST OF HLTH NCI

Contact Details

Phones:
Business:
(561) 228-2206
Emails:
Addresses:
Business Mailing:
Location A229
130 SCRIPPS WAY BLDG 2A2
Jupiter FL 33458
Business Street:
Location A229
130 SCRIPPS WAY BLDG 2A2
Jupiter FL 33458