Satyamaheshwar Peddibhotla

Satyamaheshwar Peddibhotla, Ph.D.

Research Associate Professor

Department: Pharmacodynamics
Business Phone: (352) 294-8940
Business Email: speddibhotla@ufl.edu

About Satyamaheshwar Peddibhotla

As a Research Assistant Professor in the college of Pharmacy, University of Florida, I have over 15 years of experience in synthetic/medicinal chemistry, devoted to SAR-based discovery and optimization of small molecules leads, synthesis of active pharmaceutical intermediates and proteomic probes across multiple therapeutic areas including cancer, addiction, metabolic diseases and infectious diseases. As a Senior Scientist at Sanford Burnham Prebys Medical Discovery Institute, I have led hit to lead optimization and scale up chemistry to support in vitro and in vivo studies for both phenotypic and specific target driven projects. This work contributed to 12 probes for the NIH Molecular Libraries Program (MLPCN). I have led programs to translate 4 of these probes/hits to in vivo leads under the Florida Translational Research Program (FTRP). In addition, my doctoral work focused on discovering metal-catalyzed cycloadditions aimed towards Diversity Oriented Synthesis (DOS) of heterocyclic libraries that are rich in stereochemical diversity and access novel chemical and biological space. I have also led efforts to develop a “chemical toolbox” for a direct access to natural product proteomic probes to derive SAR information and allow rapid identification of the biological targets in my post-doctoral research. This has provided me the requisite experience in data driven design of analogs, chemo- and site-selective reagent development, stereoselective synthesis, and efficient construction of heterocyclic scaffolds including metal catalyzed processes, parallel synthesis, purification, and characterization to deliver the intended molecules.

Teaching Profile

Courses Taught
2024-2025
PHA5515 Prin Med Chem-Pcol II
Teaching Philosophy
“When you teach one, two learn” Robert A. Heinlein. My teaching philosophy is based on teaching to learn, while students learn about subject matter from me, I learn how to better communicate science and engage diverse audiences from my students. My goal as teacher focuses on building knowledge, critical thinking and curiosity, key drivers of student success and to inculcate mutual respect and compassion and build good leaders of tomorrow. I encourage and challenge my students through a learner-centered and collaborative teaching practice with my students. I embrace and welcome diversity of thought, learning skills, socio-economic background and culture to foster a collaborative and inclusive environment in my classroom and workplace. I have designed, planned and organized course content, delivery, practice, assessments and utilized instructional technology and pedagogy to foster quality teaching and learning outcomes and student progress. I have sought support and advice from departmental colleagues to design and refine my classroom activities and have incorporated reflective practice based on student feedback to ensure improved outcomes. I counsel and assist students in compliance with college policies and procedures. I want to aid fruition of their academic goals, inculcate reflection, knowledge, and appreciation of self and community, making informed decisions and accountability and hope to translate their immediate goals into a lifelong goal of learning.

Research Profile

Chemokine receptors and GPCRs (G-protein coupled receptors) play crucial roles in various physiological processes, including cancer progression, immune responses, and metabolic regulation. We focus on understanding their involvement in liver and other cancers, particularly in relation to resistance mechanisms, immune modulation, tumor growth, and metastasis, is highly relevant and impactful.

Developing therapeutics targeting GPCRs holds immense potential, especially in addressing the adverse drug reactions (ADRs) associated with current therapies across multiple disease areas such as cancer, CNS disorders, cardiovascular diseases, and metabolic conditions. GPCRs are known for their druggability and diverse roles in cellular signaling, making them promising targets for novel therapeutic interventions.

In our research, we are exploring how modulation of GPCRs can enhance therapeutic efficacy, overcome resistance mechanisms, and potentially improve patient outcomes. The interdisciplinary nature of my work, spans basic drug discovery, pharmacology, molecular mechanisms and therapeutic applications and economic value, underscores its translational potential.

Open Researcher and Contributor ID (ORCID)

0000-0001-5381-0507

Areas of Interest
  • Adverse drug reactions (ADRs)
  • Chemical biology
  • Medicinal chemistry
  • Small molecule drug discovery

Publications

2024
Discovery of small molecule guanylyl cyclase B receptor positive allosteric modulators
PNAS Nexus. 3(6) [DOI] 10.1093/pnasnexus/pgae225. [PMID] 38894878.
2023
Triazolothiadiazine derivative positively modulates CXCR4 signaling and improves diabetic wound healing.
Biochemical pharmacology. 216 [DOI] 10.1016/j.bcp.2023.115764. [PMID] 37634595.
2022
An Optimized Dihydrodibenzothiazepine Lead Compound (SBI-0797750) as a Potent and Selective Inhibitor of Plasmodium falciparum and P. vivax Glucose 6-Phosphate Dehydrogenase 6-Phosphogluconolactonase
Antimicrobial Agents and Chemotherapy. 66(4) [DOI] 10.1128/aac.02109-21. [PMID] 35266827.
2022
Discovery of Anthranilic Acid Derivatives as Difluoromethylornithine Adjunct Agents That Inhibit Far Upstream Element Binding Protein 1 (FUBP1) Function
Journal of Medicinal Chemistry. 65(22):15391-15415 [DOI] 10.1021/acs.jmedchem.2c01350. [PMID] 36382923.
2022
Discovery of Small Molecule Activators of Chemokine Receptor CXCR4 That Improve Diabetic Wound Healing.
International journal of molecular sciences. 23(4) [DOI] 10.3390/ijms23042196. [PMID] 35216311.
2021
Discovery of small molecule guanylyl cyclase A receptor positive allosteric modulators
Proceedings of the National Academy of Sciences. 118(52) [DOI] 10.1073/pnas.2109386118. [PMID] 34930837.
2020
Discovery of small molecule antagonists of chemokine receptor CXCR6 that arrest tumor growth in SK-HEP-1 mouse xenografts as a model of hepatocellular carcinoma.
Bioorganic & medicinal chemistry letters. 30(4) [DOI] 10.1016/j.bmcl.2019.126899. [PMID] 31882297.
2020
β-Arrestin-Biased Allosteric Modulator of NTSR1 Selectively Attenuates Addictive Behaviors.
Cell. 181(6):1364-1379.e14 [DOI] 10.1016/j.cell.2020.04.053. [PMID] 32470395.
2019
Discovery of β-Arrestin Biased, Orally Bioavailable, and CNS Penetrant Neurotensin Receptor 1 (NTR1) Allosteric Modulators.
Journal of medicinal chemistry. 62(17):8357-8363 [DOI] 10.1021/acs.jmedchem.9b00340. [PMID] 31390201.
2018
Repurposing antimalarial aminoquinolines and related compounds for treatment of retinal neovascularization.
PloS one. 13(9) [DOI] 10.1371/journal.pone.0202436. [PMID] 30208056.
2016
ML314: A Biased Neurotensin Receptor Ligand for Methamphetamine Abuse.
ACS chemical biology. 11(7):1880-90 [DOI] 10.1021/acschembio.6b00291. [PMID] 27119457.
2016
MondoA coordinately regulates skeletal myocyte lipid homeostasis and insulin signaling.
The Journal of clinical investigation. 126(9):3567-79 [DOI] 10.1172/JCI87382. [PMID] 27500491.
2015
Discovery of ML358, a Selective Small Molecule Inhibitor of the SKN-1 Pathway Involved in Drug Detoxification and Resistance in Nematodes.
ACS chemical biology. 10(8):1871-9 [DOI] 10.1021/acschembio.5b00304. [PMID] 25946346.
2014
Imidazole-derived agonists for the neurotensin 1 receptor.
Bioorganic & medicinal chemistry letters. 24(1):262-7 [DOI] 10.1016/j.bmcl.2013.11.026. [PMID] 24332089.
2013
Discovery of ML314, a Brain Penetrant Non-Peptidic β-Arrestin Biased Agonist of the Neurotensin NTR1 Receptor.
ACS medicinal chemistry letters. 4(9):846-851 [PMID] 24611085.
2013
Synthesis and physicochemical characterization of novel phenotypic probes targeting the nuclear factor-kappa B signaling pathway.
Beilstein journal of organic chemistry. 9:900-7 [DOI] 10.3762/bjoc.9.103. [PMID] 23766805.
2012
Discovery of a Plasmodium falciparum glucose-6-phosphate dehydrogenase 6-phosphogluconolactonase inhibitor (R,Z)-N-((1-ethylpyrrolidin-2-yl)methyl)-2-(2-fluorobenzylidene)-3-oxo-3,4-dihydro-2H-benzo[b][1,4]thiazine-6-carboxamide (ML276) that reduces parasite growth in vitro.
Journal of medicinal chemistry. 55(16):7262-72 [DOI] 10.1021/jm300833h. [PMID] 22813531.
2011
Identification of Inhibitors of NOD1-Induced Nuclear Factor-κB Activation.
ACS medicinal chemistry letters. 2(10):780-785 [PMID] 22003428.
2010
Chemical biology strategy reveals pathway-selective inhibitor of NF-kappaB activation induced by protein kinase C.
ACS chemical biology. 5(3):287-99 [DOI] 10.1021/cb9003089. [PMID] 20141195.
2010
Inhibition of protein kinase C-driven nuclear factor-kappaB activation: synthesis, structure-activity relationship, and pharmacological profiling of pathway specific benzimidazole probe molecules.
Journal of medicinal chemistry. 53(12):4793-7 [DOI] 10.1021/jm1000248. [PMID] 20481485.
2010
Mild arming and derivatization of natural products via an In(OTf)3-catalyzed arene iodination.
Organic letters. 12(9):2104-7 [DOI] 10.1021/ol100587j. [PMID] 20387852.
2009
3-Substituted-3-hydroxy-2-oxindole, an Emerging New Scaffold for Drug Discovery with Potential Anti-Cancer and other Biological Activities
Current Bioactive Compounds. 5(1):20-38 [DOI] 10.2174/157340709787580900.
2008
Small molecules can selectively inhibit ephrin binding to the EphA4 and EphA2 receptors.
The Journal of biological chemistry. 283(43):29461-72 [DOI] 10.1074/jbc.M804103200. [PMID] 18728010.
2007
Simultaneous arming and structure/activity studies of natural products employing O-H insertions: an expedient and versatile strategy for natural products-based chemical genetics.
Journal of the American Chemical Society. 129(40):12222-31 [PMID] 17880073.
2006
Sensitization of cancer cells to DNA damaging agents by imidazolines.
Journal of the American Chemical Society. 128(28):9137-43 [PMID] 16834387.
2004
Sensitization of tumor cells toward chemotherapy: enhancing the efficacy of camptothecin with imidazolines.
Chemistry & biology. 11(12):1689-99 [PMID] 15610853.
2004
Stereoselective synthesis of highly substituted Delta1-pyrrolines: exo-selective 1,3-dipolar cycloaddition reactions with azlactones.
Journal of the American Chemical Society. 126(40):12776-7 [PMID] 15469263.
2003
Efficient two-step synthesis of methylphytylbenzoquinones: precursor intermediates in the biosynthesis of vitamin E
Tetrahedron Letters. 44(2):237-239 [DOI] 10.1016/s0040-4039(02)02564-9.
2003
Multicomponent Synthesisof Highly Substituted Imidazolines via a Silicon Mediated 1,3-DipolarCycloaddition
Synthesis. 2003(09):1433-1440 [DOI] 10.1055/s-2003-40196.
2002
Highly Diastereoselective Multicomponent Synthesis of Unsymmetrical Imidazolines
Organic Letters. 4(20):3533-3535 [DOI] 10.1021/ol026703y.

Grants

May 2022 ACTIVE
Preclinical development of CXCR6 antagonists to target sorafenib resistance in Hepatocellular Carcinoma
Role: Principal Investigator
Funding: NATL INST OF HLTH NCI
May 2022 ACTIVE
Novel Therapeutics for Cardiovascular Disease
Role: Co-Investigator
Funding: MAYO CLINIC via NATL INST OF HLTH NHLBI
Oct 2021 – Sep 2022
Optimize Guanyl Cyclase Receptor A Potentiators to IND-enabling Studies as Potential Cardiovascular Therapeutics
Role: Co-Project Director/Principal Investigator
Funding: ALLOROCK

Education

MS (Pharmacy – Applied Pharmacoeconomics)
2020-2022 · University of Florida, College of Pharmacy
Post-doctoral Researcher (Chemical Biology)
2005-2007 · Texas A & M University
Ph.D. (Organic/Medicinal Chemistry)
2004 · Michigan State University
MSc (Chemistry)
1995-1997 · Indian Institute of Technology, Mumbai
BSc (Chemistry)
1992-1995 · University of Mumbai

Contact Details

Phones:
Business:
(352) 294-8940
Emails:
Addresses:
Business Mailing:
PO Box 100487
GAINESVILLE FL 32610