MC-350013 and Corylin Emerge as Promising Neuroprotective Agents through Dual Targeting of xCT and GLT-1

Abraham MJ, Murtola T, Schulz R, Páll S, Smith JC, Hess B, Lindahl E (2015) GROMACS: high performance molecular simulations through multi-level parallelism from laptops to supercomputers. SoftwareX 1:19–25

Article  Google Scholar 

Abulseoud OA, Alasmari F, Hussein AM, Sari Y (2022) Ceftriaxone as a novel therapeutic agent for hyperglutamatergic states: bridging the gap between preclinical results and clinical translation. Front Neurosci 16:841036

Article  PubMed  PubMed Central  Google Scholar 

Ahamad S, Gupta D, Kumar V (2022) Targeting SARS-CoV-2 nucleocapsid oligomerization: insights from molecular docking and molecular dynamics simulations. J Biomol Struct Dyn 40(6):2430–2443

Article  CAS  PubMed  Google Scholar 

Aldakheel FM, Alduraywish SA, Dabwan KH (2025) Integrating machine learning driven virtual screening and molecular dynamics simulations to identify potential inhibitors targeting PARP1 against prostate cancer. Sci Rep 15(1):12764

Article  CAS  PubMed  PubMed Central  Google Scholar 

Alotaibi A, Travaglianti S, Wong W, Abou-Gharbia M, Childers W, Sari Y (2024) Effects of MC-100093 on ethanol drinking and the expression of astrocytic glutamate transporters in the mesocorticolimbic brain regions of male and female alcohol-preferring rats. Neuroscience 552:89–99

Article  CAS  PubMed  PubMed Central  Google Scholar 

Alsedfy MY, Ebnalwaled A, Moustafa M, Said AH (2024) Investigating the binding affinity, molecular dynamics, and ADMET properties of curcumin-IONPs as a mucoadhesive bioavailable oral treatment for iron deficiency anemia. Sci Rep 14(1):22027

Article  CAS  PubMed  PubMed Central  Google Scholar 

Alshehri MM, Danazumi AU, Alshammari MK, Bello RO, Alghazwni MK, Alshehri AM, Alshlali OM, Umar HI (2024) Repurposing the inhibitors of MMP-9 and SGLT-2 against ubiquitin specific protease 30 in parkinson’s disease: computational modelling studies. J Biomol Struct Dyn 42(3):1307–1318

Article  CAS  PubMed  Google Scholar 

Altevogt BM, Davis M, Pankevich DE (2011) Glutamate-Related biomarkers in drug development for disorders of the nervous system: Workshop summary. National Academies Press

Google Scholar 

Broni E, Striegel A, Ashley C, Sakyi PO, Peracha S, Velazquez M, Bebla K, Sodhi M, Kwofie SK, Ademokunwa A (2023) Molecular docking and dynamics simulation studies predict potential anti-ADAR2 inhibitors: implications for the treatment of cancer, neurological, immunological and infectious diseases. Int J Mol Sci 24(7):6795

Article  CAS  PubMed  PubMed Central  Google Scholar 

Dahlmanns M, Dahlmanns JK, Savaskan N, Steiner H-H, Yakubov E (2023) Glial glutamate transporter-mediated plasticity: system xc-/xCT/SLC7A11 and EAAT1/2 in brain diseases. Front Biosci-Landmark 28(3):57

Article  CAS  Google Scholar 

Daina A, Michielin O, Zoete V (2017) SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci Rep 7(1):42717

Article  PubMed  PubMed Central  Google Scholar 

Domínguez-González D, Romero-Llopis B, Roldán-Lázaro M, Baquero L, Noverques R, Pallardó FV, Navarro JA, Gonzalez-Cabo P (2024) Regulatory drugs of glutamate transporter 1 (EAAT2/GLT-1) expression and activity: role in quenching oxidative damage. Redox Experimental Medicine 2024

Duan L, Guo X, Cong Y, Feng G, Li Y, Zhang JZH (2019) Accelerated molecular dynamics simulation for helical proteins folding in explicit water. Front Chem 7:540. https://doi.org/10.3389/fchem.2019.00540

Fontana IC, Souza DG, Souza DO, Gee A, Zimmer ER, Bongarzone S (2023) A medicinal chemistry perspective on excitatory amino acid transporter 2 dysfunction in neurodegenerative diseases. J Med Chem 66(4):2330–2346

Article  CAS  PubMed  PubMed Central  Google Scholar 

García-Bueno B, Caso JR (2016) Cannabis, cannabinoid receptors, and stress-induced excitotoxicity. Neuropathology of drug addictions and substance misuse. Elsevier, pp 731–737

Green JL, Dos Santos WF, Fontana ACK (2021) Role of glutamate excitotoxicity and glutamate transporter EAAT2 in epilepsy: opportunities for novel therapeutics development. Biochem pharmacol 193:114786

Gupta A, Chaudhary N, Aparoy P (2018) MM-PBSA and per-residue decomposition energy studies on 7-Phenyl-imidazoquinolin-4 (5H)-one derivatives: identification of crucial site points at microsomal prostaglandin E synthase-1 (mPGES-1) active site. Int J Biol Macromol 119:352–359

Article  CAS  PubMed  Google Scholar 

Hakami AY, Sari Y (2017) β-lactamase inhibitor, clavulanic acid, attenuates ethanol intake and increases glial glutamate transporters expression in alcohol preferring rats. Neurosci Lett 657:140

Article  CAS  PubMed  PubMed Central  Google Scholar 

Hammad AM, Sari Y (2020) Effects of cocaine exposure on astrocytic glutamate transporters and relapse-like ethanol-drinking behavior in male alcohol-preferring rats. Alcohol Alcohol 55(3):254–263

Article  CAS  PubMed  PubMed Central  Google Scholar 

Hodos RA, Kidd BA, Shameer K, Readhead BP, Dudley JT (2016) In silico methods for drug repurposing and pharmacology. Wiley Interdiscip Rev Syst Biol Med 8(3):186–210

Article  PubMed  PubMed Central  Google Scholar 

Huang M-Y, Tu C-E, Wang S-C, Hung Y-L, Su C-C, Fang S-H, Chen C-S, Liu P-L, Cheng W-C, Huang Y-W (2018) Corylin inhibits LPS-induced inflammatory response and attenuates the activation of NLRP3 inflammasome in microglia. BMC complementary and alternative medicine 18(1):221

Article  PubMed  PubMed Central  Google Scholar 

Islam MT, Aktaruzzaman M, Barai C, Rafi FI, Hasan AR, Tasnim T, Sarder P, Albadrani GM, Al-Ghadi MQ, Sayed AA (2025) In silico screening of naturally derived dietary compounds as potential butyrylcholinesterase inhibitors for Alzheimer’s disease treatment. Sci Rep 15(1):17134

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kato T, Kusakizako T, Jin C, Zhou X, Ohgaki R, Quan L, Xu M, Okuda S, Kobayashi K, Yamashita K (2022) Structural insights into inhibitory mechanism of human excitatory amino acid transporter EAAT2. Nat Commun 13(1):4714

Article  CAS  PubMed  PubMed Central  Google Scholar 

Knackstedt LA, Wu L, Rothstein J, Vidensky S, Gordon J, Ramanjulu M, Dunman P, Blass B, Childers W, Abou-Gharbia M (2021) MC-100093, a novel β-lactam glutamate transporter-1 enhancer devoid of antimicrobial properties, attenuates cocaine relapse in rats. J Pharmacol Exp Ther 378(2):51–59

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kumari R, Kumar R, Consortium OSDD, Lynn A (2014) g_mmpbsa A GROMACS tool for high-throughput MM-PBSA calculations. J Chem Inf Model 54(7):1951–1962

Article  CAS  PubMed  Google Scholar 

Kurniawan J, Ishida T (2022) Protein model quality estimation using molecular dynamics simulation. ACS Omega 7(28):24274–24281. https://doi.org/10.1021/acsomega.2c01475

Lee SG, Su ZZ, Emdad L, Gupta P, Sarkar D, Borjabad A, Volsky DJ, Fisher PB (2008) Mechanism of ceftriaxone induction of excitatory amino acid transporter-2 expression and glutamate uptake in primary human astrocytes. J Biol Chem 283(19):13116–13123. https://doi.org/10.1074/jbc.M707697200

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lemkul JA (2024) Introductory tutorials for simulating protein dynamics with GROMACS. J Phys Chem B 128(39):9418–9435

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lewerenz J, Albrecht P, Tien MLT, Henke N, Karumbayaram S, Kornblum HI, Wiedau-Pazos M, Schubert D, Maher P, Methner A (2009) Induction of Nrf2 and xCT are involved in the action of the neuroprotective antibiotic ceftriaxone in vitro. J Neurochem 111(2):332–343

Article  CAS  PubMed  Google Scholar 

Lewerenz J, Hewett SJ, Huang Y, Lambros M, Gout PW, Kalivas PW, Massie A, Smolders I, Methner A, Pergande M, Smith SB, Ganapathy V, Maher P (2013) The cystine/glutamate antiporter system x(c)(-) in health and disease: from molecular mechanisms to novel therapeutic opportunities. Antioxid Redox Signal 18(5):522–555. https://doi.org/10.1089/ars.2011.4391

Article  CAS  PubMed  Google Scholar 

Magi S, Piccirillo S, Amoroso S, Lariccia V (2019) Excitatory amino acid transporters (EAATs): glutamate transport and beyond. Int J Mol Sci 20(22):5674

Article  CAS  PubMed  PubMed Central  Google Scholar 

Mahamba L, Isa MA, Kappo AP (2025) In Silico identification of potential inhibitors for the universal stress G4LZI3 protein from schistosoma mansoni using molecular Docking and molecular dynamics simulation analyses. Aspects Mol Med 100084

Neves D, Salazar IL, Almeida RD, Silva RM (2023) Molecular mechanisms of ischemia and glutamate excitotoxicity. Life Sci 328:121814

Article  CAS  PubMed 

Comments (0)

No login
gif