Targeting the Glucokinase–Glucokinase Regulatory Protein Axis: Pharmacophore-Based Identification of Novel Antidiabetic Small Molecules Ajita Paliwal, Sarvesh Paliwal, Swapnil Sharma, Ashwini Kumar Mishra, Smita Jain ACS Medicinal Chemistry Letters, 2026 Diabetes is the most prevalent metabolic disorder distinguished by increased blood glucose levels. Unfortunately, none of the marketed treatments can cure the ailment. Glucokinase has recently emerged as a novel target acting in both the liver and the pancreas. The activity of this novel protein in the liver is regulated by a protein called glucokinase regulatory protein (GKRP). The study aimed to identify novel GKRP modulators and evaluate their potential as antidiabetic agents using a comprehensive approach incorporating in silico, in vitro, and in vivo methods. In the quest for novel GKRP modulators, pharmacophore models were developed using Hypogen and HipHop methodologies. The optimal pharmacophore hypothesis, featuring 1HBA, 1HY, 1HBD, and 1RA, demonstrated a root mean-square deviation of 0.88 Å and a high correlation coefficient of 0.88. Fisher’s randomization and Cat Scramble tests confirmed the statistical validity of the models, with a 95% confidence level. The validated pharmacophore model was employed in a virtual screening of the NCI database, resulting in the retrieval of key hits, including NCS 1972 and NCS 80683. These compounds were subjected to docking studies and in vitro enzyme-based GKRP modulatory assay, revealing favorable binding interactions with the GKRP active site and IC 50 of 1.60 and 3.04 nM, respectively. In vivo evaluations showed that NCS 1972 (2.5 mg/kg) significantly improved lipid profiles, reduced liver hypertrophy and adiposity, and enhanced body mass index, 0.27 ± 0.02 g/mm, 0.21 ± 0.12g/mm, 0.70 ± 2.82 g/cm 2 respectively, compared to the HFD-STZ group. Histopathological analyses demonstrated substantial cellular restoration in pancreatic and liver tissues, with NCS 1972 exhibiting superior efficacy over NCS 80683. Additionally, gene expression studies revealed that both compounds corrected HFD-STZ-induced dysregulation of glucose metabolism and inflammatory markers. These findings underscore the significant therapeutic potential of NCS 1972 in mitigating diabetes, suggesting its promise as a novel antidiabetic agent.
4-(1-Methylethoxy)-N-(2-methyl-8-quinolinyl)-benzamide (CDN1163) Attenuates Glutamate-Induced Excitotoxicity by Suppressing ER Stress and Restoring Mitochondrial Dynamics in N2a Cells Vikrant Rahi, Swapnil Sharma, Ravinder K. Kaundal ACS Chemical Neuroscience, 2026 Excessive glutamate release during excitotoxic events such as stroke and neurodegeneration leads to elevated mitochondrial reactive oxygen species (ROS) production and mitochondrial membrane depolarization, contributing to dysfunction of the sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) and subsequent endoplasmic reticulum (ER) stress. SERCA is critical for maintaining ER Ca2+ homeostasis, and its impairment exacerbates ER stress and neuronal excitotoxicity. In this study, we investigated the neuroprotective potential of CDN1163 (4-(1-methylethoxy)-N-(2-methyl-8-quinolinyl)-benzamide), a small-molecule SERCA activator, in an in vitro model of glutamate-induced toxicity using N2a cells. Glutamate exposure markedly reduced cell viability and induced apoptosis, as evidenced by increased caspase-3 and Bax expression along with suppression of the antiapoptotic protein Bcl-2. These cytotoxic effects were accompanied by excessive intracellular and mitochondrial ROS generation and dissipation of the mitochondrial membrane potential (ΔΨm), indicating mitochondrial dysfunction. Glutamate further disrupted mitochondrial quality control by impairing mitophagy initiation, reflected by reduced PINK1 and Parkin expression and altered LC3-II and phospho-p62 levels. This mitochondrial impairment coincided with pronounced ER stress, characterized by activation of unfolded protein response signaling pathways, including increased expression of BiP, p-IRE1α, XBP 1s, p-PERK, p-eIF2α, ATF4, CHOP, and ATF6, together with downregulation of SERCA1a and SERCA2b, leading to ER Ca2+ dyshomeostasis. Treatment with CDN1163 significantly reversed glutamate-induced cytotoxicity by restoring cell viability, suppressing apoptosis, reducing mitochondrial and cellular ROS, stabilizing mitochondrial membrane potential, reactivating mitophagy, and alleviating ER stress through restoration of SERCA expression and ER Ca2+ homeostasis. Collectively, these findings demonstrate that CDN1163 confers neuroprotection against glutamate-induced excitotoxic injury by targeting interconnected mitochondrial and ER stress pathways, highlighting its therapeutic potential in excitotoxic neurodegenerative conditions.
mRNA-Based Therapeutics: Advances in Drug Delivery, Comparative Innovations, and Biomedical Applications Radhika Joshi, Swapnil Sharma, Devesh U. Kapoor, Bhupendra G. Prajapati, Kampanart Huanbutta, Pornsak Sriamornsak Molecular Pharmaceutics, 2026 mRNA-based therapeutics represent a major advancement in modern medicine, offering programmable and nonintegrating treatment options for infectious diseases, malignancies, and hereditary disorders. This review addresses the chronological evolution, structural optimization, and delivery challenges of mRNA drugs, highlighting developments such as nucleoside modifications and lipid nanoparticle (LNP) platforms that improve the stability and promote cellular entry. Comparative analysis highlights the benefits of mRNA over DNA-, siRNA-, and protein-based medicine in safety, scalability, and rapid rearrangement. Applications vary from COVID-19 vaccines to individualized cancer immunotherapy and protein replacement strategies. New methods, including self-amplifying mRNA (saRNA), CRISPR-Cas9 gene editing, and tissue-specific delivery systems, enhance the therapeutic potential. While mRNA technology faces challenges in terms of immunogenicity, multiple dosing, and durability of safety considerations, it offers unparalleled precision, transient expression, and swift manufacturability. This review emphasizes the comparative design principles of mRNA delivery systems, bridging formulation innovation with translational biomedical applications. By integrating lipid-based and nonlipid nanocarrier insights, it highlights critical advances shaping next-generation mRNA therapeutics.
Biomedical Applications of Alginates Payal Kesharwani, Swapnil Sharma, Vishal Chaudhary, Rajat Goyal, Rupesh K. Gautam Biopolymers for Biomedical Applications, 2024
Biogenic or Green Synthesis of Magnetic Nanoparticles Sanjana Tewari, Manisha Bhardwaj, Sonia Saini, Vivek Sharma, Swapnil Sharma, Jaya Dwivedi Functionalized Magnetic Nanoparticles for Theranostic Applications, 2024
Barriers to targeted drug delivery strategies in brain Brain Tumor Targeting Drug Delivery Systems Advanced Nanoscience for Theranostics Applications, 2023
Theranostic liposome for brain tumor diagnosis and treatment Brain Tumor Targeting Drug Delivery Systems Advanced Nanoscience for Theranostics Applications, 2023
Machine Learning and Deep Learning in Bioinformatics Swati Paliwal, Ashish Sharma, Smita Jain, Swapnil Sharma Bioinformatics and Computational Biology Technological Advancements Applications and Opportunities, 2023
Colloidosome as an Efficient Novel Drug Delivery System: An Update Advanced Pharmaceutical Herbal Nanoscience Targeted Drug Delivery System Part II, 2022
Fabrication and characterization of self-microemulsifying mouth dissolving film for effective delivery of piroxicam Indian Journal of Pharmaceutical Sciences, 2019
Formulation and development of risperidone loaded niosomes for improved bioavailability: In vitro and in vivo study Acta Poloniae Pharmaceutica Drug Research, 2017
A new self microemulsifying mouth dissolving film Seema Venkatrao Pattewar, Sanjay Bhaskar Kasture, Vishal Vivek Pande, Swapnil K. Sharma Indian Journal of Pharmaceutical Education and Research, 2016
Phytochemical analysis and antibacterial screening of Calendula officinalis (L) and Catharanthus roseus (L.) against pathogenic bacteria Indian Drugs, 2016
Novel C3 substituted 1,4 benzodiazepine derivatives as potent CCKA antagonists Der Pharma Chemica, 2015
Novel oxoketene dithioacetal based protocols to the synthesis of a series of 3- amino acids and sulpha drugs embellished analogues of the privileged 1, 4 benzodiazepines for their possible use as CCKA antagonists Der Pharma Chemica, 2015
Application of chalcone in synthesis of 1-(1, 5-benzodiazepino) substituted analogues of indole Rasayan Journal of Chemistry, 2015
Novel approach of aceclofenac fast dissolving tablet Pakistan Journal of Pharmaceutical Sciences, 2015
In vitro antioxidant and alpha-Amylase, alpha-glucosidase inhibitory activity of flowers of calotropis gigantean Indian Drugs, 2014
Comparative in-vitro transcorneal permeation studies of aqueous drop of esmolol HCL through excised goat, sheep, and buffalo corneas Pharmacologyonline, 2013
Genesis of axenfeld rieger syndrome: A review International Journal of Pharmaceutical Sciences Review and Research, 2012
Chiari Frommel syndrome - an exhaustive review International Journal of Pharmaceutical Sciences Review and Research, 2012
Synthesis and antimicrobial studies of oxazolidinone derivatives International Journal of Pharmaceutical Sciences Review and Research, 2012
Polypharmacological activities of bergenia species International Journal of Pharmaceutical Sciences Review and Research, 2012
Antioxidant potential and protection of pancreatic β- cells by Calotropis gigantea in streptozocin induced diabetic rats. Journal of Complementary Integrative Medicine, 2012
First report on laxative activity of CUCUMIS SATIVUS International Journal of Pharmaceutical Sciences Review and Research, 2012
Phytochemistry, traditional uses and cancer chemopreventive activity of Amla (Phyllanthus emblica): The Sustainer Journal of Applied Pharmaceutical Science, 2012
Evaluation of green tea on lipid profile of hypercholesterolemic patients: A case study Pharmacologyonline, 2011
Evaluation of combined herbalextractof Withania somnifera, Ocimum sanctum and Tinospora cordifolia as an chemoprotectivein cancer Pharmacologyonline, 2011
First report on laxative activity of Citrullus lanatus Pharmacologyonline, 2011
Analgesic and antipyretic activities of aqueous extract of leaves of Carissa carandas linn Pharmacologyonline, 2011
Latest developments in biomaterial interfaces and drug delivery: challenges, innovations, and future outlook S Patel, SD Salaman, DU Kapoor, R Yadav, S Sharma Zeitschrift für Naturforschung C 80 (9-10), 431-456 , 2025 2025 Citations: 6
Nyctanthes arbor-tristis Improves Blood Pressure via Endothelial Pathway: In Silico, Ex Vivo, and In Vivo Evidence A Chaturvedi, K Verma, S Jain, P Sharma, V Paliwal, S Paliwal, S Sharma Cell Biochemistry and Biophysics 83 (2), 1861-1877 , 2025 2025 Citations: 2
Identification of Sirtuin 1-Targeted Anti-Alzheimer Agents Using Structure-Based Drug Design and Multi-Database Screening: Identification of Sirtuin 1-Targeted Anti-Alzheimer … P Chandola, S Jain, R Singh, MC Jamali, J Dwivedi, S Sharma Indian Journal of Chemistry (IJC) 63 (12), 1240-1249 , 2024 2024
Biogenic or green synthesis of magnetic nanoparticles S Tewari, M Bhardwaj, S Saini, V Sharma, S Sharma, J Dwivedi Functionalized Magnetic Nanoparticles for Theranostic Applications, 39-68 , 2024 2024 Citations: 1
Functionalized Magnetic Nanoparticles for Chemotherapy Applications P Kesharwani, S Jain, K Verma, J Dwivedi, S Sharma Functionalized Magnetic Nanoparticles for Theranostic Applications, 377-416 , 2024 2024 Citations: 1
Multifunctional Cellulose-Based Adsorbent from Waste Wood Wool for Heavy Metal Removal and Bacterial Disinfection: Insights into Adsorption Behavior, and DFT Calculations M Bhardwaj, S Jaiswal, N Misra, N Kumari, S Shukla, J Dwivedi, ... 2024
Carbon nanodots: An illuminating paradigm in production, characterization, and oncological targeting methodologies—a review BG Prajapati, V Pandey, S Sharma, S Patel, DP Shah, DU Kapoor BioNanoScience 14 (4), 4322-4341 , 2024 2024 Citations: 12
BACE1 inhibitors: A promising therapeutic approach for the management of Alzheimer’s disease R Arya, S Jain, S Paliwal, K Madan, S Sharma, A Mishra, P Tiwari, ... Asian Pacific Journal of Tropical Biomedicine 14 (9), 369-381 , 2024 2024 Citations: 13
Nano-mediated molecular targeting in diagnosis and mitigation of Wilson disease A Chaturvedi, S Sharma, R Shukla Molecular Neurobiology 61 (7), 4240-4258 , 2024 2024 Citations: 5
Tissue regeneration properties of hydrogels derived from biological macromolecules: A review P Kesharwani, A Alexander, R Shukla, S Jain, A Bisht, K Kumari, K Verma, ... International Journal of Biological Macromolecules 271, 132280 , 2024 2024 Citations: 43
One-pot synthesis of condensed azepines K Bhardwaj, S Jaiswal, A Bhardwaj, D Kishore, J Dwivedi, S Sharma Current Organic Chemistry 28 (11), 815-829 , 2024 2024 Citations: 12
Harnessing polyelectrolyte complexes for precision cancer targeting: a comprehensive review BG Prajapati, JB Sharma, S Sharma, ND Trivedi, M Gaur, DU Kapoor Medical Oncology 41 (6), 145 , 2024 2024 Citations: 14
Green synthesized AgNPs as a probe for colorimetric detection of Hg (II) ions in aqueous medium and fluorescent imaging in liver cell lines and its antibacterial activity S Tewari, S Sahani, N Yaduvanshi, R Painuli, N Sankararamakrishnan, ... Discover Nano 19 (1), 78 , 2024 2024 Citations: 14
Biomedical applications of alginates P Kesharwani, S Sharma, V Chaudhary, R Goyal, RK Gautam Biopolymers for Biomedical Applications, 53-86 , 2024 2024 Citations: 3
Gelatin-based Hydrogels for Drug Delivery: A Recent Update D Kapoor, K Verma, S Jain, S Sharma Biomaterial-based Hydrogels: Therapeutics Carrier and Tissue Regeneration, 67-87 , 2024 2024 Citations: 10
Current insight on the role of glucokinase and glucokinase regulatory protein in diabetes A Paliwal, V Paliwal, S Jain, S Paliwal, S Sharma Mini Reviews in Medicinal Chemistry 24 (7), 674-688 , 2024 2024 Citations: 18
Preparation, evaluation, and in vitro studies of sustained-release topical hydrogel of Curcuma longa L. targeting skin disorders A Narwaria, AK Chakrabarty, S Bishayee, S Mohanty, D Banerjee, ... International Journal of Ayurveda Research 5 (2), 94-107 , 2024 2024 Citations: 4
Neuroprotective Effects of Carotenoid Rich Verbesina encelioides Flower Extract in Scopolamine Induced Memory Impaired Rats Mimicking Alzheimer’s Disease A Dey, N Srivastava, S Sharma, V Verma, L Rao, M Chaudhary, S Jain, ... Preprints , 2024 2024
Tinospora cordifolia ameliorates paclitaxel-induced neuropathic pain in albino rats P Joshi, S Patel, A Paliwal, S Jain, K Verma, J Dwivedi, S Sharma Journal of Ethnopharmacology 321, 117559 , 2024 2024 Citations: 8
Insights on synthetic strategies and structure-activity relationship of donepezil and its derivatives S Patel, S Jain, R Gururani, S Sharma, J Dwivedi Medicinal Chemistry Research 33 (3), 370-405 , 2024 2024 Citations: 19
MOST CITED SCHOLAR PUBLICATIONS
Biomedical applications of hydrogels in drug delivery system: An update P Kesharwani, A Bisht, A Alexander, V Dave, S Sharma Journal of Drug Delivery Science and Technology 66, 102914 , 2021 2021 Citations: 336
Ethosomes and ultradeformable liposomes for transdermal delivery of clotrimazole: a comparative assessment RGS Maheshwari, RK Tekade, PA Sharma, G Darwhekar, A Tyagi, ... Saudi pharmaceutical journal 20 (2), 161-170 , 2012 2012 Citations: 292
Lipid-polymer hybrid nanoparticles: Development & statistical optimization of norfloxacin for topical drug delivery system V Dave, RB Yadav, K Kushwaha, S Yadav, S Sharma, U Agrawal Bioactive materials 2 (4), 269-280 , 2017 2017 Citations: 170
Diversified potentials of Ocimum sanctum Linn (Tulsi): An exhaustive survey E Singh, S Sharma, J Dwivedi, S Sharma J Nat Prod Plant Resour 2 (1), 39-48 , 2012 2012 Citations: 142
Flurbiprofen loaded ethosomes-transdermal delivery of anti-inflammatory effect in rat model S Paliwal, A Tilak, J Sharma, V Dave, S Sharma, R Yadav, S Patel, ... Lipids in health and disease 18 (1), 133 , 2019 2019 Citations: 129
Fluoride: A review of pre-clinical and clinical studies D Sharma, A Singh, K Verma, S Paliwal, S Sharma, J Dwivedi Environmental toxicology and pharmacology 56, 297-313 , 2017 2017 Citations: 124
Coating technologies in pharmaceutical product development D Kapoor, R Maheshwari, K Verma, S Sharma, P Ghode, RK Tekade Drug delivery systems, 665-719 , 2020 2020 Citations: 91
Clitoria ternatea Mediated Synthesis of Graphene Quantum Dots for the Treatment of Alzheimer’s Disease K Tak, R Sharma, V Dave, S Jain, S Sharma ACS Chemical Neuroscience 11 (22), 3741-3748 , 2020 2020 Citations: 90
Polypharmacological activities of Bergenia species KM Ruby, R Chauhan, S Sharma, J Dwivedi International Journal of Pharmaceutical Sciences Review and Research 13 (1 … , 2012 2012 Citations: 89
Formulation of risperidone loaded proniosomes for effective transdermal delivery: An in-vitro and in-vivo study S Sambhakar, S Paliwal, S Sharma, B Singh Bulletin of faculty of pharmacy, Cairo University 55 (2), 239-247 , 2017 2017 Citations: 78
Curcumin: an insight into molecular pathways involved in anticancer activity P Joshi, S Joshi, D Semwal, A Bisht, S Paliwal, J Dwivedi, S Sharma Mini reviews in medicinal chemistry 21 (17), 2420-2457 , 2021 2021 Citations: 72
The synthetic and biological attributes of pyrazole derivatives: A review J Dwivedi, S Sharma, S Jain, A Singh Mini Reviews in Medicinal Chemistry 18 (11), 918-947 , 2018 2018 Citations: 70
Cedrus deodara (Roxb. ex D. Don) G. Don: A review of traditional use, phytochemical composition and pharmacology A Bisht, S Jain, A Misra, J Dwivedi, S Paliwal, S Sharma Journal of ethnopharmacology 279, 114361 , 2021 2021 Citations: 69
Neuroprotective role of oral vitamin D supplementation on consciousness and inflammatory biomarkers in determining severity outcome in acute traumatic brain injury patients: a … S Sharma, A Kumar, A Choudhary, S Sharma, L Khurana, N Sharma, ... Clinical drug investigation 40 (4), 327-334 , 2020 2020 Citations: 69
Green Synthesis of Colloidal Copper Nanoparticles Capped with Tinospora cordifolia and Its Application in Catalytic Degradation in Textile Dye: An Ecologically … P Sharma, S Pant, P Poonia, S Kumari, V Dave, S Sharma Journal of Inorganic and Organometallic Polymers and Materials 28 (6), 2463-2472 , 2018 2018 Citations: 68
Metabolic syndrome: the constellation of co-morbidities, a global threat K Madan, S Paliwal, S Sharma, S Kesar, N Chauhan, M Madan Endocrine, Metabolic & Immune Disorders-Drug Targets (Formerly Current Drug … , 2023 2023 Citations: 65
Green synthesis and characterization of silver nanoparticles by Allium cepa L. to produce silver nano‐coated fabric and their antimicrobial evaluation P Sharma, S Pant, S Rai, RB Yadav, S Sharma, V Dave Applied organometallic chemistry 32 (3), e4146 , 2018 2018 Citations: 62
GSK-3β and its inhibitors in Alzheimer's disease: a recent update N Chauhan, S Paliwal, S Jain, K Verma, S Paliwal, S Sharma Mini reviews in medicinal chemistry 22 (22), 2881-2895 , 2022 2022 Citations: 61
Microparticulate and nanotechnology mediated drug delivery system for the delivery of herbal extracts SK Dubey, S Parab, VPK Achalla, A Narwaria, S Sharma, ... Journal of Biomaterials Science, Polymer Edition 33 (12), 1531-1554 , 2022 2022 Citations: 56
A facile one pot synthesis of novel pyrimidine derivatives of 1, 5-benzodiazepines via domino reaction and their antibacterial evaluation A Misra, S Jain, D Kishore, V Dave, KR Reddy, V Sadhu, J Dwivedi, ... Journal of microbiological methods 163, 105648 , 2019 2019 Citations: 55