Better understanding of biomolecules as drug target: a literature review
Abstract
Drugs are small biological therapeutic agents that play a crucial role in enhancing human health. They have been widely used in the treatment of various diseases, with conventional medicine being one of the most common approaches. However, conventional medicine has several limitations, including non-specific drug targeting, limited efficacy, low stability, poor absorption rates, and degradation due to enzymatic activity and low pH in the digestive system. Efforts to improve drug targeting have led to the development of molecular-based therapies, particularly through the use of biomolecules as drug targets. Drug targeting aims to optimize therapeutic effects by focusing on specific targets while minimizing side effects. This review article explores research findings from the PubMed database, applying specific inclusion and exclusion criteria. It discusses the types of drugs and biomolecular targets, including G protein-coupled receptors (GPCRs), enzymes, ion channel receptors, and DNA, as well as the mechanisms through which drugs interact with these targets in the treatment of various diseases. Additionally, the advantages and disadvantages of these biomolecular targets are examined. In conclusion, the four biomolecules discussed each present unique characteristics as drug targets, highlighting the importance of carefully selecting appropriate molecules based on an understanding of their functions, properties, and interactions with drugs in the body.
References
Karaman R. Commonly used drugs - uses, side effects, bioavailability & approaches to improve it. New York: Nova Science Publishers Inc., 2015; 1-293.
https://doi.org/10.13140/RG.2.1.1444.4640
Glynn J, Bhikha RAH. Herbal products and conventional drugs – an uneasy alliance. Int J Human Health Sci (IJHHS) 2018; 2(4):193.
https://doi.org/10.31344/ijhhs.v2i4.55
Karimi A, Majlesi M, Rafieian-Kopaei M. Herbal versus synthetic drugs; beliefs and facts. J Nephropharmacol, 2015; 4(1):27-30.
Patel S, Sadhu P, Kumari M, Dash DK, Jain S, Sen AK. A review on anticancer agents: conventional drugs and novel target specific inhibitors. Orient J Chem, 2023; 39(3):657-69.
https://doi.org/10.13005/ojc/390316
Nazli A, He DL, Liao D, Khan MZI, Huang C, He Y. Strategies and progresses for enhancing targeted antibiotic delivery. Adv Drug Deliv Rev, 2022; 189:114502.
https://doi.org/10.1016/j.addr.2022.114502
Vasan N, Baselga J, Hyman DM. A view on drug resistance in cancer. Nature, 2019; 575(7782):299-309.
https://doi.org/10.1038/s41586-019-1730-1
Aminu N, Bello I, Umar NM, Tanko N, Aminu A, Audu MM. The influence of nanoparticulate drug delivery systems in drug therapy. J Drug Deliv Sci Technol, 2020; 60(Suppl 1):101961.
https://doi.org/10.1016/j.jddst.2020.101961
Bhutani U, Basu T, Majumdar S. Oral drug delivery: conventional to long acting new-age designs. Eur J Pharm Biopharm 2021; 162:23-42.
https://doi.org/10.1016/j.ejpb.2021.02.008
Sivamaruthi BS, Nallasamy PK, Sivakumar S, Kesika P, Chaiyasut C. Pharmaceutical and biomedical applications of starch-based drug delivery system: A review. J Drug Deliv Sci Technol, 2022; 77(3):103890.
https://doi.org/10.1016/j.jddst.2022.103890
Farjadian F, Ghasemi A, Gohari O, Roointan A, Karimi M, Hamblin MR. Nanopharmaceuticals and nanomedicines currently on the market: challenges and opportunities. Nanomedicine (Lond) 2019; 14(1):93-126.
https://doi.org/10.2217/nnm-2018-0120
Karel P. Molecular drug targets and drug delivery. Open Access J Cancer Oncol, 2017; 1(2).
https://doi.org/10.23880/OAJCO-16000107
Laurieri N, Delgoda R. Novel targets in drug discovery. Pharmacognosy, 2017; 617-32.
https://doi.org/ 10.1016/B978-0-12-802104-0.00031-7
Gao D, Chen Q, Zeng Y, Jiang M, Zhang Y. Applications of machine learning in drug target discovery. Curr Drug Metab, 2020; 21(10):790-803.
https://doi.org/10.2174/1567201817999200728142023
Muhamadejevs R, Živković L, Dzintare M, Sjakste N. DNA-binding activities of compounds acting as enzyme inhibitors, ion channel blockers and receptor binders. Chem Biol Interact, 2021; 348:109638.
https://doi.org/10.1016/j.cbi.2021.109638
Prabahar K, Alanazi Z, Qushawy M. Targeted drug delivery system: advantages, carriers and strategies. IJPER, 2021; 55(2):346-53.
Walker JKL, Penn RB, Hanania NA, Dickey BF, Bond RA. New perspectives regarding β(2)-adrenoceptor ligands in the treatment of asthma. Br J Pharmacol 2011; 163(1):18-28.
https://doi.org/10.1111/j.1476-5381.2010.01178.x
Pollock M, Sinha IP, Hartling L, Rowe BH, Schreiber S, Fernandes RM. Inhaled short-acting bronchodilators for managing emergency childhood asthma: an overview of reviews. Allergy 2017; 72(2):183-200.
https://doi.org/10.1111/all.13039
Miller PD, Hattersley G, Riis BJ, Williams GC, Lau E, Russo LA, et al. Effect of abaloparatide vs placebo on new vertebral fractures in postmenopausal women with osteoporosis: a randomized clinical trial. JAMA, 2016; 316(7):722-33.
https://doi.org/10.1001/jama.2016.11136
Nauck MA, Petrie JR, Sesti G, Mannucci E, Courrèges JP, Lindegaard ML, et al. A phase 2, randomized, dose-finding study of the novel once-weekly human glp-1 analog, semaglutide, compared with placebo and open-label liraglutide in patients with type 2 diabetes. Diabetes Care, 2016; 39(2):231-41.
https://doi.org/10.2337/dc15-0165
Yin J, Mobarec JC, Kolb P, Rosenbaum DM. Crystal structure of the human OX2 orexin receptor bound to the insomnia drug suvorexant. Nature, 2015; 519(7542):247-50.
https://doi.org/10.1038/nature14035
Block GA, Bushinsky DA, Cheng S, Cunningham J, Dehmel B, Drueke TB, et al. Effect of etelcalcetide vs cinacalcet on serum parathyroid hormone in patients receiving hemodialysis with secondary hyperparathyroidism: a randomized clinical trial. JAMA, 2017; 317(2):156-64.
https://doi.org/10.1001/jama.2016.19468
Ishima T, Futamura T, Ohgi Y, Yoshimi N, Kikuchi T, Hashimoto K. Potentiation of neurite outgrowth by brexpiprazole, a novel serotonin-dopamine activity modulator: a role for serotonin 5-HT1A and 5-HT2A receptors. Eur Neuropsychopharmacol, 2015; 25(4):505-11.
https://doi.org/10.1016/j.euroneuro.2015.01.014
Rymer JA, Bhatt DL, Angiolillo DJ, Diaz M, Garratt KN, Waksman R, et al. Cangrelor use patterns and transition to oral P2Y12 inhibitors among patients with myocardial infarction: initial results from the cameo registry. J Am Heart Assoc, 2022; 11(11):e024513.
https://doi.org/10.1161/JAHA.121.024513
Xiao T, Ren S, Bao J, Gao D, Sun R, Gu X, et al. Vorapaxar proven to be a promising candidate for pulmonary fibrosis by intervening in the PAR1/JAK2/STAT1/3 signaling pathway-an experimental in vitro and vivo study. Eur J Pharmacol, 2023; 943:175438.
https://doi.org/10.1016/j.ejphar.2022.175438
Kokhan VS, Anokhin PK, Abaimov DA, Shamakina IY, Soldatov VO, Deykin AV. Neurokinin-1 receptor antagonist rolapitant suppresses anxiety and alcohol intake produced by repeated withdrawal episodes. FEBS J, 2022; 289(16):5021-9.
https://doi.org/10.1111/febs.16400
Kamarova M, Baig S, Patel H, Monks K, Wasay M, Ali A, et al. Antiplatelet use in ischemic stroke. Ann Pharmacother, 2022; 56(10):1159-73.
https://doi.org/10.1177/10600280211073009
Hirota T, Fujita Y, Ieiri I. An updated review of pharmacokinetic drug interactions and pharmacogenetics of statins. Expert Opin Drug Metab Toxicol, 2020; 16(9):809-22.
https://doi.org/10.1080/17425255.2020.1801634
Cutrell S, Alhomoud IS, Mehta A, Talasaz AH, Van Tassell B, Dixon DL. Ace-inhibitors in hypertension: a historical perspective and current insights. Curr Hypertens Rep, 2023; 25(9):243-50.
https://doi.org/10.1007/s11906-023-01248-2
Rao SS, Manabe N, Karasawa Y, Hasebe Y, Nozawa K, Nakajima A, et al. Comparative profiles of lubiprostone, linaclotide, and elobixibat for chronic constipation: a systematic literature review with meta-analysis and number needed to treat/harm. BMC Gastroenterol, 2024; 24(1):12.
https://doi.org/10.1186/s12876-023-03104-8
White WB, Saag KG, Becker MA, Borer JS, Gorelick PB, Whelton A, et al. Cardiovascular safety of febuxostat or allopurinol in patients with gout. N Engl J Med, 2018; 378(13):1200-10.
https://doi.org/10.1056/NEJMoa1710895
Griffith EC, Wallace MJ, Wu Y, Kumar G, Gajewski S, Jackson P, et al. The structural and functional basis for recurring sulfa drug resistance mutations in Staphylococcus aureus dihydropteroate synthase. Front Microbiol, 2018; 9:1369.
https://doi.org/10.3389/fmicb.2018.01369
Raimondi M, Randazzo O, La Franca M, Barone G, Vignoni E, Rossi D, et al. DHFR inhibitors: reading the past for discovering novel anticancer agents. Molecules, 2019; 24(6):1140.
https://doi.org/10.3390/molecules24061140
Yoshihara A, Luo Y, Ishido Y, Usukura K, Oda K, Sue M, et al. Inhibitory effects of methimazole and propylthiouracil on iodotyrosine deiodinase 1 in thyrocytes. Endocr J, 2019; 66(4):349-57.
https://doi.org/10.1507/endocrj.EJ18-0380
Makullah M, Ellis DA, Jones M, Steele C. Hematopoietic 12/15-lipoxygenase activity negatively contributes to fungal-associated allergic asthma. Am J Physiol Lung Cell Mol Physiol, 2023; 325(2):L104-13.
https://doi.org/10.1152/ajplung.00090.2023
Silverman RB. Design and Mechanism of GABA aminotransferase inactivators. Treatments for epilepsies and addictions. Chem Rev, 2018; 118(7):4037-70.
https://doi.org/10.1021/acs.chemrev.8b00009
Singhal K, Sandhir R. L-type calcium channel blocker ameliorates diabetic encephalopathy by modulating dysregulated calcium homeostasis. J Neurosci Res, 2015; 93(2):296-308.
https://doi.org/10.1002/jnr.23478
Grosskopf I, Shaish A, Charach G, Harats D, Kamari Y. Nifedipine treatment for hypertension is associated with enhanced lipolytic activity and accelerated clearance of postprandial lipemia. Horm Metab Res, 2016; 48(4):257-62.
https://doi.org/10.1055/s-0035-1565180
Huang J, Fan X, Jin X, Teng L, Yan N. Dual-pocket inhibition of Nav channels by the antiepileptic drug lamotrigine. Proc Natl Acad Sci USA, 2023; 120(41):e2309773120.
https://doi.org/10.1073/pnas.2309773120
Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, Hantel S, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med, 2016; 373(22):2117-28.
https://doi.org/10.1056/NEJMoa1504720
Lo AC, Ruiz JA, Koenig CM, Anderson BM, Olson KM, Triche EW. Effects of dalfampridine on multi-dimensional aspects of gait and dexterity in multiple sclerosis among timed walk responders and non-responders. J Neurol Sci, 2015; 356(1-2):77-82.
https://doi.org/10.1016/j.jns.2015.06.008
Zhou Q, Chen PC, Devaraneni PK, Martin GM, Olson EM, Shyng SL. Carbamazepine inhibits ATP-sensitive potassium channel activity by disrupting channel response to MgADP. Channels, 2014; 8(4):376-82.
https://doi.org/10.4161/chan.29117
Tarcha EJ, Olsen CM, Probst P, Peckham D, Muñoz-Elías EJ, Kruger JG, et al. Safety and pharmacodynamics of dalazatide, a Kv1.3 channel inhibitor, in the treatment of plaque psoriasis: A randomized phase 1b trial. PloS One, 2017; 12(7):e0180762.
https://doi.org/10.1371/journal.pone.0180762
Shen W, Alshehri M, Desale S, Wilcox C. The effect of amiloride on proteinuria in patients with proteinuric kidney disease. Am J Nephrol, 2021; 52(5):368-77.
https://doi.org/10.1159/000515809
Balestrini A, Joseph V, Dourado M, Reese RM, Shields SD, Rougé L, et al. A TRPA1 inhibitor suppresses neurogenic inflammation and airway contraction for asthma treatment. J Exp Med, 2021; 218(4):e20201637.
https://doi.org/10.1084/jem.20201637
Bruen C, Al-Saadi M, Michelson EA, Tanios M, Mendoza-Ayala R, Miller J, et al. Auxora vs. placebo for the treatment of patients with severe COVID-19 pneumonia: a randomized-controlled clinical trial. Crit Care, 2022; 26(1):101.
https://doi.org/10.1186/s13054-022-03964-8
Lau CH, Seow KM, Chen KH. The molecular mechanisms of actions, effects, and clinical implications of PARP inhibitors in epithelial ovarian cancers: a systematic review. Int J Mol Sci 2022; 23(15):8125.
https://doi.org/10.3390/ijms23158125
Yap TA, Fontana E, Lee EK, Spigel DR, Højgaard M, Lheureux S, et al. Camonsertib in DNA damage response-deficient advanced solid tumors: phase 1 trial results. Nat Med, 2023; 29(6):1400-11.
https://doi.org/10.1038/s41591-023-02399-0
Gu L, Hickey RJ, Malkas LH. Therapeutic targeting of DNA replication stress in cancer. Genes (Basel), 2023; 14(7):1346.
https://doi.org/10.3390/genes14071346
Lachowiez C, DiNardo CD, Konopleva M. Venetoclax in acute myeloid leukemia - current and future directions. Leuk Lymphoma, 2020; 61(6):1313-22.
https://doi.org/10.1080/10428194.2020.1719098
Hoy SM. Talazoparib: first global approval. Drugs, 2018; 78(18):1939-46.
https://doi.org/10.1007/s40265-018-1026-z
Han M, Deng C. BDNF as a pharmacogenetic target for antipsychotic treatment of schizophrenia. Neurosci Lett, 2020; 726:133870.
https://doi.org/10.1016/j.neulet.2018.10.015
Okajima D, Yasuda S, Maejima T, Karibe T, Sakurai K, Aida T, et al. Datopotamab deruxtecan, a novel TROP2-directed antibody-drug conjugate, demonstrates potent antitumor activity by efficient drug delivery to tumor cells. Mol Cancer Ther 2021; 20(12):2329-40.
https://doi.org/10.1158/1535-7163
Shi GM, Huang XY, Wu D, Sun HC, Liang F, Ji Y, et al. Toripalimab combined with lenvatinib and GEMOX is a promising regimen as first-line treatment for advanced intrahepatic cholangiocarcinoma: a single-center, single-arm, phase 2 study. Signal Transduct Target Ther, 2023; 8(1):106.
https://doi.org/10.1038/s41392-023-01317-7
Sakata Y, Sakata S, Oya Y, Tamiya M, Suzuki H, Shibaki R, et al. Osimertinib as first-line treatment for advanced epidermal growth factor receptor mutation-positive non-small-cell lung cancer in a real-world setting (OSI-FACT). Eur J Cancer, 2021; 159:144-53.
https://doi.org/10.1016/j.ejca.2021.09.041
Gu L, Hickey RJ, Malkas LH. Therapeutic targeting of dna replication stress in cancer. Genes (Basel), 2023; 14(7):1346.
https://doi.org/10.3390/genes14071346
Zhang X, Yu W, Li Y, Wang A, Cao H, Fu Y. Drug development advances in human genetics‐based targets. Med Comm, 2024; 5(2):e481.
https://doi.org/10.1002/mco2.481
Ritter JM, Flower RJ, Henderson G, Loke YK, MacEwan D, Rang HP. Rang & Dale’s Pharmacology. Elsevier Health Sciences; 2018.
Santos R, Ursu O, Gaulton A, Bento AP, Donadi RS, Bologa CG, et al. A comprehensive map of molecular drug targets. Nat Rev Drug Discov, 2016; 16(1):19-34.
https://doi.org/10.1038/nrd.2016.230
Cacace A, Banks M, Spicer T, Civoli F, Watson J. An ultra-HTS process for the identification of small molecule modulators of orphan G-protein-coupled receptors. Drug Discov Today, 2003; 8(17):785-92.
https://doi.org/10.1016/s1359-6446(03)02809-5
Mansfield R, Able S, Griffin P, Irvine B, James I, Macartney M, Dorr P. CCR5 pharmacology methodologies and associated applications. Methods Enzymol, 2009; 460:17-55.
https://doi.org/10.1016/s0076-6879(09)05202-1
Tuteja N. Signaling through G protein coupled receptors. Plant Signal Behav, 2009; 4(10):942-7.
https://doi.org/10.4161/psb.4.10.9530
Baldwin JM. Structure and function of receptors coupled to G proteins. Curr Opin Cell Biol, 1994; 6(2):180-90.
https://doi: 10.1016/0955-0674(94)90134-1
Hauser AS, Attwood MM, Rask-Andersen M, Schiöth HB, Gloriam DE. Trends in GPCR drug discovery: new agents, targets and indications. Nat Rev Drug Discov, 2017; 16(12):829-42.
https://doi.org/10.1038/nrd.2017.178
Cheng L, Xia F, Li Z, Shen C, Yang Z, Hou H, et al. Structure, function and drug discovery of GPCR signaling. Mol Biomed, 2023; 4(1):46.
https://doi.org/10.1186/s43556-023-00156-w
Wang L, Zhou C, Zhu D, Wang X, Fang L, Zhong J, et al. Serotonin-1A receptor alterations in depression: a meta-analysis of molecular imaging studies. BMC Psychiatry, 2016; 16(1):319.
https://doi.org/10.1186/s12888-016-1025-0
Zięba A, Stępnicki P, Matosiuk D, Kaczor AA. Overcoming depression with 5-HT2A receptor ligands. Int J Mol Sci, 2021; 23(1):10.
https://doi.org/10.3390/ijms23010010
Cattaneo M. P2Y12 receptors: structure and function. J Thromb Haemost, 2015; 13 Suppl 1:S10-6.
https://doi.org/10.1111/jth.12952
Wang L, Wang J, Xu J, Qin W, Wang Y, Luo S, et al. The role and molecular mechanism of P2Y12 receptors in the pathogenesis of atherosclerotic cardiovascular diseases. Appl Sci, 2021; 11(19):9078.
https://doi.org/10.3390/app11199078
Alexander SPH, Benson HE, Faccenda E, Pawson AJ, Sharman JL, Spedding M, et al. The concise guide to PHARMACOLOGY 2013/14: G protein-couple receptors. Br J Pharmacol, 2013; 170(8):1459-581.
https://doi.org/10.1111/bph.12445
Pal K, Melcher K, Xu HE. Structure and mechanism for recognition of peptide hormones by Class B G-protein-coupled receptors. Acta Pharmacol Sin, 2012; 33(3):300-11.
https://doi.org/10.1038/aps.2011.170
Esbrit P, Alcaraz MJ. Current perspectives on parathyroid hormone (PTH) and PTH-related protein (PTHrP) as bone anabolic therapies. Biochem Pharmacol, 2013; 85(10):1417-23.
https://doi.org/10.1016/j.bcp.2013.03.002
Canalis E, Giustina A, Bilezikian JP. Mechanisms of anabolic therapies for osteoporosis. N Engl J Med, 2007; 357(9):905-16.
https://doi.org/10.1056/NEJMra067395
Wright SC, Kozielewicz P, Kowalski-Jahn M, Petersen J, Bowin CF, Slodkowicz G, et al. A conserved molecular switch in Class F receptors regulates receptor activation and pathway selection. Nat Commun, 2019; 10(1):667.
https://doi.org/10.1038/s41467-019-08630-2
Schulte G, Kozielewicz P. Structural insight into class F receptors - What have we learnt regarding agonist-induced activation? Basic Clin Pharmacol Toxicol, 2020; 126(Suppl 6):17-24.
https://doi.org/10.1111/bcpt.13235
Cho YM, Merchant CE, Kieffer TJ. Targeting the glucagon receptor family for diabetes and obesity therapy. Pharmacol Ther, 2012; 135(3):247-78.
https://doi.org/10.1016/j.pharmthera.2012.05.009
Akhtar N, Ahad A, Khar RK, Jaggi M, Aqil M, Iqbal Z, et al. The emerging role of P-glycoprotein inhibitors in drug delivery: a patent review. Expert Opin Ther Pat, 2011; 21(4):561-76.
https://doi.org/10.1517/13543776.2011.561784
Dimitrov D. Virus entry: molecular mechanisms and biomedical applications. Nat Rev Microbiol, 2004; 2(2):109-22.
https://doi.org/10.1038/nrmicro817
Abdulkhalek S, Hrynyk, Szewczuk M. A novel G-protein-coupled receptor-signaling platform and its targeted translation in human disease. Res Reports Biochem, 2013; 2013(3):17-30.
https://doi.org/10.2147/RRBC.S28430
Pan X, Veroniaina H, Su N, Sha K, Jiang F, Wu Z, et al. Applications and developments of gene therapy drug delivery systems for genetic diseases. Asian J Pharm Sci, 2021; 16(6):687-703.
https://doi.org/10.1016/j.ajps.2021.05.003
Mugumbate G, Jackson GE, van der Spoel D. Open conformation of adipokinetic hormone receptor from the malaria mosquito facilitates hormone binding. Peptides, 2011; 32(3):553-9.
https://doi.org/10.1016/j.peptides.2010.08.017
Rufer AC. Drug discovery for enzymes. Drug Discov Today, 2021; 26(4):875-86.
https://doi.org/10.1016/j.drudis.2021.01.006
Agarwal P, Huckle J, Newman J, Reid DL. Trends in small molecule drug properties: A developability molecule assessment perspective. Drug Discov Today, 2022; 27(12):103366.
https://doi.org/10.1016/j.drudis.2022.103366
Rask-Andersen M, Almén MS, Schiöth HB. Trends in the exploitation of novel drug targets. Nat Rev Drug Discov, 2011; 10(8):579-90.
https://doi.org/10.1038/nrd3478
Ouertani A, Neifar M, Ouertani R, Mosbah A, Masmoudi A, Cherif A. Effectiveness of enzyme inhibitors in biomedicine and pharmacotherapy. Adv Tissue Engin Regen Med, 2019; 5(2):85-90.
https://doi.org/10.15406/atroa.2019.05.00104
Deodhar M, Al Rihani SB, Arwood MJ, Darakjian L, Dow P, Turgeon J, et al. Mechanisms of CYP450 inhibition: understanding drug-drug interactions due to mechanism-based inhibition in clinical practice. Pharmaceutics, 2020; 12(9):846.
https://doi.org/10.3390/pharmaceutics12090846
Hong SJ, Lee YJ, Lee SJ, Hong BK, Kang WC, Lee JY, et al. Treat-to-target or high-intensity statin in patients with coronary artery disease: a randomized clinical trial. JAMA, 2023; 329(13):1078-87.
https://doi.org/10.1001/jama.2023.2487
Rothwell PM, Algra A, Chen Z, Diener HC, Norrving B, Mehta Z. Effects of aspirin on risk and severity of early recurrent stroke after transient ischaemic attack and ischaemic stroke: time-course analysis of randomised trials. Lancet, 2016; 388(10042):365-75.
https://doi.org/10.1016/S0140-6736(16)30468-8
Turberville A, Semple H, Davies G, Ivanov D, Holdgate GA. A perspective on the discovery of enzyme activators. SLAS Discov, 2022; 27(8):419-27.
https://doi.org/10.1016/j.slasd.2022.09.001
Peng LH, Fang JY, Dai N, Shen XZ, Yang YL, Sun J, et al. Efficacy and safety of linaclotide in patients with irritable bowel syndrome with constipation: Chinese sub‐cohort analysis of a phase III, randomized, double‐blind, placebo‐controlled trial. J Dig Dis, 2022; 23(2):99-110.
https://doi.org/10.1111/1751-2980.13081
Singh K, Gupta JK, Pathak D, Kumar S. The use of enzyme inhibitors in drug discovery: current strategies and future prospects. Currt Enzyme Inhib, 2023; 19(3):157-66.
https://doi.org/10.2174/1573408019666230731113105
de la Fuente M, Lombardero L, Gómez-González A, Solari C, Angulo-Barturen I, Acera A, et al. Enzyme therapy: current challenges and future perspectives. Int J Mol Sci, 2021; 22(17):9181.
https://doi.org/10.3390/ijms22179181
Bagal SK, Brown AD, Cox PJ, Omoto K, Owen RM, Pryde DC, et al. Ion channels as therapeutic targets: A drug discovery perspective. J Med Chem, 2013; 56(3):593-624.
https://doi.org/10.1021/jm3011433
Imbrici P, Liantonio A, Camerino GM, De Bellis M, Camerino C, Mele A, et al. Therapeutic approaches to genetic ion channelopathies and perspectives in drug discovery. Front Pharmacol, 2016; 7:121.
https://doi.org/10.3389/fphar.2016.00121
Connick P, De Angelis F, Parker RA, Plantone D, Doshi A, John N, et al. Multiple Sclerosis-Secondary Progressive Multi-Arm Randomisation Trial (MS-SMART): A multiarm phase IIb randomised, double-blind, placebo-controlled clinical trial comparing the efficacy of three neuroprotective drugs in secondary progressive multiple sclerosis. BMJ Open, 2018; 8(8):e021944.
https://doi.org/10.1136/bmjopen-2018-021944
Ma K, Cheng Z, Jiang H, Lin Z, Liu C, Liu X, et al. Expert consensus on ion channel drugs for chronic pain treatment in China. J Pain Res, 2024; 17:953-63.
https://doi.org/10.2147/JPR.S445171
Corry B, Thomas M. Mechanism of ion permeation and selectivity in a voltage gated sodium channel. J Am Chem Soc, 2012; 134(3):1840-6.
https://doi.org/10.1021/ja210020h
Zamponi GW. Targeting voltage-gated calcium channels in neurological and psychiatric diseases. Nat Rev Drug Discov, 2016; 15(1):19-34.
https://doi.org/10.1038/nrd.2015.5
Guo M, Shen W, Zhou M, Song Y, Liu J, Xiong W, et al. Safety and efficacy of carbamazepine in the treatment of trigeminal neuralgia: A metanalysis in biomedicine. Math Biosci Eng, 2024; 21(4):5335-59.
https://doi.org/10.3934/mbe.2024235
Zhang M, Gao CX, Ma KT, Li L, Dai ZG, Wang S, et al. A meta-analysis of therapeutic efficacy and safety of gabapentin in the treatment of postherpetic neuralgia from randomized controlled trials. Biomed Res Int, 2018; 2018:7474207.
https://doi.org/10.1155/2018/7474207
Lemoine D, Jiang R, Taly A, Chataigneau T, Specht A, Grutter T. Ligand-gated ion channels: New insights into neurological disorders and ligand recognition. Chem Rev, 2012; 12(12):6285-318.
https://doi.org/10.1021/cr3000829
Keramidas A, Moorhouse AJ, Schofield PR, Barry PH. Ligand-gated ion channels: Mechanisms underlying ion selectivity. Prog Biophys Mol Biol, 2004; 86(2):161-204.
https://doi.org/10.1016/j.pbiomolbio.2003.09.002
Tariot PN, Farlow MR, Grossberg GT, Graham SM, McDonald S, Gregel I. Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil: a randomized controlled trial. JAMA, 2004; 291(3):317-24.
https://doi.org/10.1001/jama.291.3.317
Levinson SR, Luo S, Henry MA. The role of sodium channels in chronic pain. Muscle Nerve, 2012; 46(2):155-65.
https://doi.org/10.1002/mus.23314
Palomino-Doza J, Rahman TJ, Avery PJ, Mayosi BM, Farrall M, Watkins H, et al. Ambulatory blood pressure is associated with polymorphic variation in P2X receptor genes. Hypertension, 2008; 52(5):980-5.
https://doi.org/10.1161/HYPERTENSIONAHA.108.113282
Singh S, Malik BK, Sharma DK. Molecular drug targets and structure-based drug design: A holistic approach. Bioinformation, 2006; 1(8):314-20.
https://doi.org/10.6026/97320630001314
Nurmagfirah N. Asam nukleat, protein, enzim, reseptor sebagai target kerja obat dan tranduksi signal. Makasar: Universitas Islam Negeri (UIN) Alauddin, 2014.
Zhang X, Yu W, Li Y, Wang A, Cao H, Fu Y. Drug development advances in human genetics‐based targets. MedComm, 2024; 5(2):e481.
