About

Abhisheak Sharma is a trained analytical scientist, pharmacokineticist, and pharmacist whose research focuses on the pharmacokinetic studies of new chemical entities, bioactive natural products, and complex botanicals. He serves as Associate Chair and Assistant Professor of Pharmaceutics and Co-Director for the Translational Drug Development Core at the University of Florida, Gainesville. Dr. Sharma received his B. Pharm. from Mohan Lal Sukhadia University in 2006 and became a registered pharmacist in India. He earned his M. Pharm. in pharmaceutical chemistry from U. P. Technical University with a MHRD-Post-graduate fellowship, and his Ph.D. in pharmacokinetics & metabolism from CSIR-Central Drug Research Institute. His post-doctoral research was conducted at the University of Mississippi and the University of Florida. His research interests include in vivo and in vitro preclinical pharmacokinetic studies of new chemical entities and natural products, bioanalytical method development and validation, and translational development of new chemical entities to candidate drugs using PK-PD modeling and simulation. Dr. Sharma has published more than sixty peer-reviewed articles and one book chapter in the field of pharmacokinetics and drug discovery.

Research topics

• Chemistry
• Pharmacology
• Biology
• Stereochemistry
• Internal medicine
• Medicine
• Biochemistry
• Anesthesia
• Psychology

Selected publications

• Physiologically Based Pharmacokinetic Model for Clinical Translation and Prediction of Drug Interaction of the Major Kratom Alkaloid, Mitragynine

  ACS Pharmacology & Translational Science · 2026-01-13

  articleOpen accessSenior authorCorresponding

  The opioid crisis presents a significant public health issue and underscores the urgency of developing effective treatments for opioid use disorder (OUD). Mitragynine (MTG), the major active alkaloid found in kratom (Mitragyna speciosa), presents as a potential OUD therapy. A physiologically based pharmacokinetic (PBPK) model has been established to support first-in-human (FIH) dose selection and assess potential drug–drug interactions (DDIs). Extensive physicochemical and in vitro studies were performed to define MTG’s pharmacokinetic properties for the model. The model was validated through in vivo pharmacokinetic studies (intravenous and oral) in both male and female Sprague–Dawley rats, revealing sex-related pharmacokinetic differences. Further validation in nonrodent models included pharmacokinetic studies in female beagle dogs. Utilizing this model, single and multiple-dose simulations of MTG (either as the pure compound or as the major alkaloid present in kratom) administration in humans were conducted, predicting the plasma concentration–time profiles of MTG and its active metabolite, 7-hydroxymitragynine (7-HMG) to facilitate dose selection. The model also evaluates MTG’s potential as both a victim and perpetrator in drug interactions, considering its effects with CYP3A4 and CYP2D6 inhibitors and substrates. Simulation results indicate that potent CYP3A4 and CYP2D6 inhibitors have minimal impact on MTG exposure. However, coadministration with CYP3A4 inhibitors leads to a reduction in 7-HMG formation. As a perpetrator, MTG has negligible effects on CYP2D6 substrates but increases midazolam exposure by 2.2 to 2.7-fold. This comprehensive model supports the therapeutic development of MTG.

  PublisherOA PDFDOI

• Figure S2 from Oral IRAK-4 Inhibitor CA-4948 Is Blood-Brain Barrier Penetrant and Has Single-Agent Activity against CNS Lymphoma and Melanoma Brain Metastases

  2025-11-25

  articleOpen access

  <p>Supplemental Figure 2. CA-4948 affinity for murine IRAK-4.</p>

  PublisherOA PDFDOI

• Figure S3 from Oral IRAK-4 Inhibitor CA-4948 Is Blood-Brain Barrier Penetrant and Has Single-Agent Activity against CNS Lymphoma and Melanoma Brain Metastases

  2025-11-25

  articleOpen access

  <p>Supplemental Figure 3. Active IRAK-4 expression in intracranial tumors.</p>

  PublisherOA PDFDOI

• List of contributors

  Elsevier eBooks · 2025-09-27

  book-chapter
  PublisherDOI

• From Kratom to Semi‐Synthetic Opioids: The Rise and Risks of MGM‐15

  Drug Testing and Analysis · 2025-09-11 · 3 citations

  articleSenior authorCorresponding

  Kratom (Mitragyna speciosa), a plant native to Southeast Asia, has long been used for its stimulant and analgesic properties. 7-Hydroxymitragynine (7-HMG) is a potent and selective opioid agonist in vitro and demonstrates a potent opioid effect in living subjects, reversible by naloxone. It has been semi-synthesized into products that are readily available in retail and virtual shops. It is known that 7-HMG has earned the nickname "legal morphine," and has gained popularity among users seeking pain relief and/or a "high" comparable with prescription opioids. Medicinal chemistry efforts have led to synthetic 7-HMG derivatives such as MGM-15, where stereospecific saturation of the imine N(1)-C(2) double bond increases opioid receptor affinity and activity. Despite its higher in vitro opioid potency, MGM-15 is currently sold in the US for human consumption as a "research chemical" in tablet form, even though there is an absence of this being studied in humans and obviously no FDA approval. In this study, we analyzed commercially available MGM-labeled tablets using UPLC-MS/MS and subsequently evaluated the binding affinities of purified MGM-15 across multiple opioid receptors. Tablets contained an average of 10.9 ± 0.2 mg (10.7 to 11.2 mg) of MGM-15, with no naturally occurring kratom alkaloids or illicit substances detected. MGM-15 shows greater hMOR and hDOR binding affinities than 7-HMG, indicating the potential for higher opioid effects and risks, emphasizing the urgent need for more research to advise regulation and hopefully prevent misuse and harm.

  PublisherDOI

• Discovery of CRBN-recruiting PROTAC degraders of the METTL3-METTL14 complex

  Medicinal Chemistry Research · 2025-09-05 · 3 citations

  articleOpen access

  Abstract METTL3 and METTL14, key components of the m 6 A writer complex, are frequently overexpressed in various malignancies, including acute myeloid leukemia (AML), where aberrant methylation has been linked to the upregulation of oncogenic transcription. Therefore, targeting the METTL3/METTL14 complex represents a potential therapeutic approach for AML. Although several METTL3 inhibitors have been discovered, their SAM-competitive mode of action often results in reduced cellular potency, prompting interest in alternative strategies such as targeted protein degradation. In this article, we expand upon reported METTL3/METTL14 complex degraders through exploration of CRBN-recruiting proteolysis-targeting chimeras (PROTACs) from multiple exit vectors of UZH2, a reported METTL3 inhibitor. The most potent PROTAC, 4j , demonstrated sub-micromolar degradation potency in MV4.11 cells with DC 50 values of 0.44 µM for METTL3 and 0.13 µM for METTL14. Notably, 4j showed enhanced cytotoxicity in MV4.11 cells compared to well-validated METTL3 inhibitors, underscoring the therapeutic potential of targeted degradation of the METTL3/METTL14 complex in AML.

  PublisherOA PDFDOI

• Figure S5 from Oral IRAK-4 Inhibitor CA-4948 Is Blood-Brain Barrier Penetrant and Has Single-Agent Activity against CNS Lymphoma and Melanoma Brain Metastases

  2025-11-25

  articleOpen access

  <p>Supplemental Figure 5: Chromatogram of CA-4948.</p>

  PublisherOA PDFDOI

• Uncaria attenuata and its main corynanthean alkaloid, villocarine A, exert antinociceptive effects in rats via activation of central μ-opioid receptors

  Journal of Ethnopharmacology · 2025-08-15 · 2 citations

  article
  PublisherDOI

• Figure S7 from Oral IRAK-4 Inhibitor CA-4948 Is Blood-Brain Barrier Penetrant and Has Single-Agent Activity against CNS Lymphoma and Melanoma Brain Metastases

  2025-11-25

  articleOpen access

  <p>Supplemental Figure 7. Pattern of pNF-κB expression in human CNS tumors.</p>

  PublisherOA PDFDOI

• Dual Opioid–Neuropeptide FF Small Molecule Ligands Demonstrate Analgesia with Reduced Tolerance Liabilities

  Molecules · 2025-07-03

  articleOpen access

  Neuropeptide FF (NPFF) receptor antagonists prevent morphine-mediated antinociceptive tolerance, and compounds with dual mu opioid receptor (MOR) agonist and NPFF antagonist activity produce antinociception without tolerance. Compounds synthesized showed affinities in radioligand competition binding assays in the nM and µM range at the opioid and NPFF receptors, respectively, and displayed substitution-dependent functional profiles in the [35S]GTPγS functional assay. From six compounds screened in vivo for antinociception and ability to prevent NPFF-induced hyperalgesia in mouse warm water tail withdrawal tests, compound 22b produced dose-dependent MOR-mediated antinociception with an ED50 value (and 95% confidence interval) of 6.88 (4.71–9.47) nmol, i.c.v., and also prevented NPFF-induced hyperalgesia. Meanwhile, 22b did not demonstrate the respiratory depression, hyperlocomotion, or impaired intestinal transit of morphine. Moreover, repeated treatment with 22b produced a 1.6-fold rightward shift in antinociceptive dose response, significantly less acute antinociceptive tolerance than morphine. Evaluated for microsomal stability in vitro and in vivo pharmacokinetic profile, 22b showed suitable microsomal stability paired in vivo with a large apparent volume of distribution and a clearance smaller than the hepatic flow in rats, suggesting no extra-hepatic metabolism. In conclusion, the present study confirms that dual-action opioid–NPFF ligands may offer therapeutic promise as analgesics with fewer liabilities of use.

  PublisherDOI

Frequent coauthors

• Christopher R. McCurdy

  172 shared

• Raju S. Kanumuri

  University of Florida

  168 shared

• Jawahar Lal

  139 shared

• Swati Jaiswal

  91 shared

• Mahendra Shukla

  84 shared

• Lance Richard McMahon

  Texas Tech University

  75 shared

• Francisco León

  University of Florida

  75 shared

• Shyam H. Kamble

  Syngene International (India)

  74 shared

Labs

• Translational Drug Development CorePI

Education

• Other, Pharmacy

  Mohan Lal Sukhadia University

  2006

• Other, Pharmaceutical Chemistry

  U. P. Technical University

• Ph.D., Pharmacokinetics & Metabolism

  CSIR-Central Drug Research Institute

Awards & honors

• Teaching & Service Award 2025 UF College of Pharmacy
• Media Excellence Award 2024 UF College of Pharmacy
• UF/IFAS High Impact Research Publication Award 2021 UF-Insti…
• Champions of CUR 2020 UF Center for Undergraduate Research
• Translational Research in Addiction Travel Award 2017