Multidisciplinary Training for Fostering Next-Generation Medicinal Chemists

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Learn More CiteCitationCitation and abstractCitation and referencesMore citation options ShareShare onFacebookX (Twitter)WeChatLinkedInRedditEmailJump toExpandCollapse EditorialOctober 7, 2024Multidisciplinary Training for Fostering Next-Generation Medicinal ChemistsClick to copy article linkArticle link copied!Bin Yu*Bin YuCollege of Chemistry, Pingyuan Laboratory, State Key Laboratory of Antiviral Drugs, Zhengzhou University, Zhengzhou 450001, China*e-mail: [email protected]More by Bin Yuhttps://orcid.org/0000-0002-7207-643XXiaoyun Lu*Xiaoyun LuSchool of Pharmacy, Jinan University, Guangzhou 510632, China*e-mail: [email protected]More by Xiaoyun Luhttps://orcid.org/0000-0001-7931-6873Junbiao Chang*Junbiao ChangCollege of Chemistry, Pingyuan Laboratory, State Key Laboratory of Antiviral Drugs, Zhengzhou University, Zhengzhou 450001, China*e-mail: [email protected]More by Junbiao Changhttps://orcid.org/0000-0001-6236-1256Open PDFJournal of Medicinal ChemistryCite this: J. Med. Chem. 2024, XXXX, XXX, XXX-XXXClick to copy citationCitation copied!https://pubs.acs.org/doi/10.1021/acs.jmedchem.4c02316https://doi.org/10.1021/acs.jmedchem.4c02316Published October 7, 2024 Publication History Received 27 September 2024Published online 7 October 2024editorialPublished 2024 by American Chemical Society. This publication is available under these Terms of Use. Request reuse permissionsThis publication is licensed for personal use by The American Chemical Society. ACS PublicationsPublished 2024 by American Chemical SocietyThe field of medicinal chemistry has evolved and transformed significantly in both industrial and academic sectors over the past decades, (1) seeing a paradigm shift from traditional follow-on drug discovery to innovative drug discovery, especially in developing countries like China. (2) Today, medicinal chemists work on developing not only small molecules but also biologics including peptides, conjugates such as antibody–drug conjugates (ADCs) and antibody–oligonucleotide conjugates (AOCs), etc. The progress made in drug discovery is evident from groundbreaking therapies in fields like oncology and immunotherapy. Advances in techniques such as structure-based drug design (SBDD), artificial intelligence (AI), targeted protein degradation such as proteolysis targeting chimeras (PROTACs) and molecular glues, DNA-encoded chemical libraries (DECLs), molecular editing, macrocyclization, and diversity-oriented synthesis (DOS) have significantly accelerated the drug discovery and development process and will revolutionize the practice of drug discovery and development. (3) Despite significant progress in drug discovery over the past few decades, many diseases like neurodegenerative disorders and certain cancers continue to resist current therapeutic approaches. The fact is that while various therapeutics, including small molecules and biologics, may show promise in early stages, they often end up failing in clinical trials due to efficacy or safety concerns. Therefore, policy makers and educational institutions should update the current training programs to prepare young medicinal chemists to address such challenges in modern drug discovery.While the landscape of drug discovery has expanded, organic synthesis remains a key capability and bottleneck in drug discovery projects. (4) Historically, drug discovery efforts have primarily focused on synthesizing and optimizing small molecules, especially natural products (e.g., penicillin). In 1943, Alexander Fleming stated to the Royal Society that, "The chemists will fasten on the molecule and modify it, as they have done with the sulfanilamide molecule in the last 5 years, so that derivatives of penicillin will appear more powerful, or with wider applications, and diseases now untouched will be conquered." (5) In the history of antibacterial drug discovery, chemical synthesis enabled the discovery of the first antibacterial substances. By strategically applying modern chemical synthesis techniques, scientists have created new antibiotics with improved potency and safety and a broader antibacterial spectrum. (6) Another representative example is the antimalarial drug artemisinin─its discovery led to the subsequent discovery of many derivatives with broad clinical applications. (7) In 2016, an analysis by Dean G. Brown et al. showed that the current practice of medicinal chemistry heavily depends on three commonly used reactions: amide bond formation, Suzuki–Miyaura coupling, and SNAr reactions (see a wish list for organic chemistry for more details at https://www.chemistryworld.com/news/the-five-reactions-on-every-organic-chemists-wish-list/3010150.article), leading to an overwhelming amount of specific molecular shapes and limited diversity in chemical space. (8) In a recent post, Abhishaike Mahajan stated that generative machine learning in chemistry is bottlenecked by synthesis as well. (9) In addition to small molecules, biologics such as ADCs also rely on chemical expertise to create linkers that couple the antibody with a small-molecule drug. (10) Thus, innovations in synthetic chemistry are key to success in all phases of drug discovery and development and will reshape the practice of drug discovery. (11)Modern synthetic chemistry techniques have enriched the toolkit for synthesis and formed the foundation of today's pharmaceutical industry. Molecular editing, a chemical version of gene editing, has opened up new opportunities for precisely modifying molecular structures. (12,13) Photochemistry has enabled the efficient synthesis of complex structures, significantly expanding the coverage of chemical space. (14) Flow chemistry techniques are increasingly utilized in drug discovery to cost-effectively access structurally diverse small-molecule analogs, including active pharmaceutical ingredients (APIs), along with previously underused or inaccessible chemistries for creating chemical diversity. (15) Rationally macrocyclizing a privileged scaffold such as pyrimidine intramolecularly (normally under the guidance of X-ray crystal structures) produces macrocyclic drugs such as pacritinib, an FDA-approved macrocycle for treating adults with myelofibrosis. (16) Deuruxolitinib, a deuterated version (H/D exchange) of ruxolitinib targeting JAK1/2, received FDA approval as a first-line treatment for adults with moderate to severe alopecia areata. (17) Adding a fluorine atom at the 2′-position enhances acidic stability, while introducing a 4′-azido group makes modified nucleosides like azvudine active against resistant HIV strains. (18) More examples are available but not exhaustively listed here. It is essential for the general public to appreciate the roles of chemistry in drug discovery practices and acknowledge that "chemists invent drugs and drugs save lives". (19)Changes in the landscape of drug discovery have impacted medicinal chemistry training. As we look ahead, training medicinal chemists becomes crucial for sustained innovation in drug discovery. (20) Traditionally, pursuing a career in medicinal chemistry involved obtaining a Ph.D. in organic chemistry and acquiring medicinal chemistry training through industry experience. There are various opinions on the content of a medicinal chemistry course, but a key component is still the ability to create and optimize molecules for enhanced drug-like properties (e.g., potency, selectivity, safety, pharmacokinetics profile, etc.). Total synthesis is believed to provide valuable training in academia for those interested in practicing modern medicinal chemistry within the pharmaceutical industry. (21) This includes the development of novel and complex drug structures like Lenacapavir (a first-in-class, long-acting HIV-1 capsid inhibitor for treating HIV-1 infection) (22) and other densely functionalized drug molecules, as well as other therapeutic modalities such as oligonucleotides, oligopeptides, oligosaccharides, and ADCs. The discipline now embraces an increasingly complex environment shaped by technological advances. In addition to conventional medicinal chemistry curricula, educational institutions should update their training programs to include property-based drug design, (23) case studies (e.g., closed-loop undergraduate training aimed at identifying boron-containing β-lactamase inhibitors), (24) and the latest techniques (e.g., AI) in drug discovery. Lectures on successful drug discovery case studies, showcasing the bench-to-bedside process, are a key component of a top-notch medicinal chemistry course (for example, the featured articles in the Drug Annotation section and article collections from different countries, as well as those categorized as Editor's Choice in the Journal of Medicinal Chemistry). There are many valuable online webinars, invited talks at international conferences, and monographs related to drug discovery for teaching purposes (details are not provided here)─introduction of the latest techniques will ensure that young medicinal chemists are prepared to leverage the most recent advancements in their future drug discovery projects. (We are pleased to see that content on AI in drug discovery has been included in medicinal chemistry textbooks used in China, and there are also several Chinese monographs available on AI.) Medicinal chemists should utilize both traditional and cutting-edge techniques to design novel drugs for tomorrow's therapeutics.Although synthetic chemistry plays a crucial role in drug discovery, drug discovery is no longer solely dominated by chemists. Other key subjects such as biology and medicine are also essential, leading to increasingly blurred boundaries between these disciplines in the field of drug discovery. (25) The challenge lies in training medicinal chemists to communicate and collaborate across related disciplines. Thus, young medicinal chemists should have a basic knowledge of a variety of disciplines, including biology, pharmacology, pharmacokinetics, toxicology, computational sciences, and beyond, rather than acquiring in-depth knowledge of a specific discipline (e.g., chemistry or biology). Integrating biology into medicinal chemistry curricula is seen as an effective method to cultivate drug discovery talents. (26) Cross-disciplinary education will enable medicinal chemists to collaborate effectively with experts from other fields, fostering innovation through teamwork. With drug discovery now a multidisciplinary effort, medicinal chemistry training programs should emphasize collaborations, ensuring that young medicinal chemists can contribute effectively to multidisciplinary teams, as interdisciplinary collaboration is essential for overcoming complex challenges in drug discovery. Medicinal chemists must collaborate closely with biologists, pharmacologists, and clinicians to translate early-stage compounds into viable drug candidates. For instance, understanding disease biology helps medicinal chemists design molecules that target the right targets or pathways, while feedback from experts on pharmacokinetics and toxicity can guide lead optimization efforts (and vice versa). However, these statements may spark some debates─some may argue that young medicinal chemists should receive in-depth training within a specific discipline. Those who specialize can excel in a particular area and possess the skills needed to manage the essential aspects of medicinal chemistry.Nowadays, medicinal chemistry training faces several challenges. Medicinal chemistry is not just an academic field─it is also an applied science with significant industrial implications. A gap often exists between academic training and the practical demands of drug discovery in the pharmaceutical industry. Conventional medicinal chemistry courses frequently focus on basic principles without sufficient exposure to real-world bench-to-bedside challenges. Chemists lacking a background in medicinal chemistry need to acquire the necessary skills for an industrial environment. Internships, industrial collaborations, and problem-based learning projects (e.g., lectures on property-based drug design and optimization; for an example, see the Drug Hunter Flash Talk titled "The Medicinal Chemist's Guide to Solving ADMET Challenges" by Patrick Schnider; more talks can be found at https://drughunter.com/flashtalks) can provide valuable exposure to real-world drug discovery challenges. Partnerships with pharmaceutical companies can provide medicinal chemistry students with exposure to the realities of drug discovery. Collaborative research projects, internships, and guest lectures from industry professionals can bridge the gap between academic learning and practical application.The future of drug discovery depends on a next generation of medicinal chemists who are equipped not only with a deep understanding of chemistry but also with the ability to collaborate across disciplines and adapt to new technologies. A medicinal chemist who is willing to learn new technologies (e.g., AI (27)) will be better positioned in this evolving world. (There are many approaches to achieving this goal, for example, via distance learning. (28)) By modernizing educational programs, fostering interdisciplinary collaboration, and providing hands-on experience, we can prepare future medicinal chemists to tackle complex challenges of drug discovery and develop novel breakthrough therapies of tomorrow.Author InformationClick to copy section linkSection link copied!Corresponding AuthorsBin Yu, J. Med. Chem. Early Career Board, College of Chemistry, Pingyuan Laboratory, State Key Laboratory of Antiviral Drugs, Zhengzhou University, Zhengzhou 450001, China, https://orcid.org/0000-0002-7207-643X, Email: [email protected]Xiaoyun Lu, J. Med. Chem. Editorial Advisory Board, School of Pharmacy, Jinan University, Guangzhou 510632, China, https://orcid.org/0000-0001-7931-6873, Email: [email protected]Junbiao Chang, College of Chemistry, Pingyuan Laboratory, State Key Laboratory of Antiviral Drugs, Zhengzhou University, Zhengzhou 450001, China, https://orcid.org/0000-0001-6236-1256, Email: [email protected]NotesViews expressed in this editorial are those of the authors and not necessarily the views of the ACS.AcknowledgmentsClick to copy section linkSection link copied!The authors acknowledge financial support from the National Scientific and Technological Innovation 2030 Major Project (no. 2023ZD0507704) and National Natural Science Foundation of China (nos. 22277110 and 82473761). We apologize for not citing all relevant work and omitting some important topics, and we sincerely thank everyone dedicated to medicinal chemistry education and drug discovery.ReferencesClick to copy section linkSection link copied! This article references 28 other publications. 1 Looking back and moving forward in medicinal chemistry. Nat. Commun. 2023, 14 (1), 4299. DOI: 10.1038/s41467-023-39949-6 Google ScholarThere is no corresponding record for this reference.2Yu, B.; Ouyang, L. Journal of Medicinal Chemistry Collection: Drug Discovery in China. J. Med. Chem. 2024, 67 (17), 14700– 14701, DOI: 10.1021/acs.jmedchem.4c01922 Google ScholarThere is no corresponding record for this reference.3Gong, Q.; Song, J.; Song, Y.; Tang, K.; Yang, P.; Wang, X.; Zhao, M.; Ouyang, L.; Rao, L.; Yu, B.; Zhan, P.; Zhang, S.; Zhang, X. New techniques and strategies in drug discovery (2020–2024 update). Chin. Chem. Lett. 2024, 110456 DOI: 10.1016/j.cclet.2024.110456 Google ScholarThere is no corresponding record for this reference.4Blakemore, D. C.; Castro, L.; Churcher, I.; Rees, D. C.; Thomas, A. W.; Wilson, D. M.; Wood, A. Organic synthesis provides opportunities to transform drug discovery. Nat. 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There is also a need for new reactions that enable non-traditional disconnections, more C-H bond activation and late-stage functionalization, as well as stereoselectively substituted aliph. heterocyclic ring synthesis, C-X or C-C bond formation. We also emphasize that syntheses compatible with biomacromols. will find increasing use, while new technologies such as machine-assisted approaches and artificial intelligence for synthesis planning have the potential to dramatically accelerate the drug-discovery process. We believe that increasing collaboration between academic and industrial chemists is crucial to address the challenges outlined here. >> More from SciFinder ®https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXos1Sktrk%253D&md5=f6269ea8193e28416fd86fe8afbcea3f5Sheehan, J. C. 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Chem. synthesis enabled the development of the first antibacterial substances, organoarsenicals and sulfa drugs, but these were soon outshone by a host of more powerful and vastly more complex antibiotics from nature: penicillin, streptomycin, tetracycline, and erythromycin, among others. These primary defences are now significantly less effective as an unavoidable consequence of rapid evolution of resistance within pathogenic bacteria, made worse by widespread misuse of antibiotics. For decades medicinal chemists replenished the arsenal of antibiotics by semisynthetic and to a lesser degree fully synthetic routes, but economic factors have led to a subsidence of this effort, which places society on the precipice of a disaster. We believe that the strategic application of modern chem. synthesis to antibacterial drug discovery must play a crit. role if a crisis of global proportions is to be averted. >> More from SciFinder ®https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhtV2jurnO&md5=4e2740493583670d655c91b1e9eee67f7Wang, J.; Xu, C.; Wong, Y. K.; Li, Y.; Liao, F.; Jiang, T.; Tu, Y. Artemisinin, the Magic Drug Discovered from Traditional Chinese Medicine. Engineering 2019, 5 (1), 32– 39, DOI: 10.1016/j.eng.2018.11.011 Google ScholarThere is no corresponding record for this reference.8Brown, D. G.; Boström, J. Analysis of Past and Present Synthetic Methodologies on Medicinal Chemistry: Where Have All the New Reactions Gone?. J. Med. Chem. 2016, 59 (10), 4443– 4458, DOI: 10.1021/acs.jmedchem.5b01409 Google Scholar8Analysis of Past and Present Synthetic Methodologies on Medicinal Chemistry: Where Have All the New Reactions Gone?Brown, Dean G.; Bostrom, JonasJournal of Medicinal Chemistry (2016), 59 (10), 4443-4458CODEN: JMCMAR; ISSN:0022-2623. (American Chemical Society) A review. An anal. of chem. reactions used in current medicinal chem. (2014), three decades ago (1984), and in natural product total synthesis has been conducted. The anal. revealed that of the current most frequently used synthetic reactions, none were discovered within the past 20 years and only two in the 1980s and 1990s (Suzuki-Miyaura and Buchwald-Hartwig). This suggests an inherent high bar of impact for new synthetic reactions in drug discovery. The most frequently used reactions were amide bond formation, Suzuki-Miyaura coupling, and SNAr reactions, most likely due to com. availability of reagents, high chemoselectivity, and a pressure on delivery. The authors show that these practices result in overpopulation of certain types of mol. shapes to the exclusion of others using simple PMI plots. The authors hope that these results will help catalyze improvements in integration of new synthetic methodologies as well as new library design. >> More from SciFinder ®https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhvVeqsrzM&md5=fd56ba8418f6d4e8c271f4e977ee2a939Mahajan, A. Generative ML in chemistry is bottlenecked by synthesis. Owl Posting, Sept 16, 2024. https://www.owlposting.com/p/generative-ml-in-chemistry-is-bottlenecked (accessed Sept 24, 2024).Google ScholarThere is no corresponding record for this reference.10Sasso, J. M.; Tenchov, R.; Bird, R.; Iyer, K. A.; Ralhan, K.; Rodriguez, Y.; Zhou, Q. A. The Evolving Landscape of Antibody-Drug Conjugates: In Depth Analysis of Recent Research Progress. Bioconjugate Chem. 2023, 34 (11), 1951– 2000, DOI: 10.1021/acs.bioconjchem.3c00374 Google ScholarThere is no corresponding record for this reference.11Campos, K. R.; Coleman, P. J.; Alvarez, J. C.; Dreher, S. D.; Garbaccio, R. M.; Terrett, N. K.; Tillyer, R. D.; Truppo, M. D.; Parmee, E. R. The importance of synthetic chemistry in the pharmaceutical industry. Science 2019, 363 (6424), eaat0805 DOI: 10.1126/science.aat0805 Google ScholarThere is no corresponding record for this reference.12Ma, C.; Lindsley, C. W.; Chang, J.; Yu, B. Rational Molecular Editing: A New Paradigm in Drug Discovery. J. Med. Chem. 2024, 67 (14), 11459– 11466, DOI: 10.1021/acs.jmedchem.4c01347 Google ScholarThere is no corresponding record for this reference.13Li, E. Q.; Lindsley, C. W.; Chang, J.; Yu, B. Molecular Skeleton Editing for New Drug Discovery. J. Med. Chem. 2024, 67 (16), 13509– 13511, DOI: 10.1021/acs.jmedchem.4c01841 Google ScholarThere is no corresponding record for this reference.14Zhu, W. F.; Empel, C.; Pelliccia, S.; Koenigs, R. M.; Proschak, E.; Hernandez-Olmos, V. Photochemistry in Medicinal Chemistry and Chemical Biology. J. Med. Chem. 2024, 67 (6), 4322– 4345, DOI: 10.1021/acs.jmedchem.3c02109 Google ScholarThere is no corresponding record for this reference.15Mansfield, A. Creating chemical diversity with flow chemistry. Drug Discovery & Development, Mar 21, 2024. https://www.drugdiscoverytrends.com/flow-chemistry-expands-chemical-diversity-drug-discovery(accessed Sept 24, 2024).Google ScholarThere is no corresponding record for this reference.16William, A. D.; Lee, A. C.; Blanchard, S.; Poulsen, A.; Teo, E. L.; Nagaraj, H.; Tan, E.; Chen, D.; Williams, M.; Sun, E. T.; Goh, K. C.; Ong, W. C.; Goh, S. K.; Hart, S.; Jayaraman, R.; Pasha, M. K.; Ethirajulu, K.; Wood, J. M.; Dymock, B. W. Discovery of the macrocycle 11-(2-pyrrolidin-1-yl-ethoxy)-14,19-dioxa-5,7,26-triaza-tetracyclo[19.3.1.1(2,6).1(8,12)]heptacosa-1(25),2(26),3,5,8,10,12(27),16,21,23-decaene (SB1518), a potent Janus kinase 2/fms-like tyrosine kinase-3 (JAK2/FLT3) inhibitor for the treatment of myelofibrosis and lymphoma. J. Med. Chem. 2011, 54 (13), 4638– 4658, DOI: 10.1021/jm200326p Google Scholar16Discovery of the Macrocycle 11-(2-Pyrrolidin-1-yl-ethoxy)-14,19-dioxa-5,7,26-triaza-tetracyclo[19.3.1.1(2,6).1(8,12)]heptacosa-1(25),2(26),3,5,8,10,12(27),16,21,23-decaene (SB1518), a Potent Janus Kinase 2/Fms-Like Tyrosine Kinase-3 (JAK2/FLT3) Inhibitor for the Treatment of Myelofibrosis and LymphomaWilliam, Anthony D.; Lee, Angeline C.-H.; Blanchard, Stephanie; Poulsen, Anders; Teo, Ee Ling; Nagaraj, Harish; Tan, Evelyn; Chen, Dizhong; Williams, Meredith; Sun, Eric T.; Goh, Kee Chuan; Ong, Wai Chung; Goh, Siok Kun; Hart, Stefan; Jayaraman, Ramesh; Pasha, Mohammed Khalid; Ethirajulu, Kantharaj; Wood, Jeanette M.; Dymock, Brian W.Journal of Medicinal Chemistry (2011), 54 (13), 4638-4658CODEN: JMCMAR; ISSN:0022-2623. (American Chemical Society) Discovery of the activating mutation V617F in Janus Kinase 2 (JAK2V617F), a tyrosine kinase critically involved in receptor signaling, recently ignited interest in JAK2 inhibitor therapy as a treatment for myelofibrosis (MF). Herein, we describe the design and synthesis of a series of small mol. 4-aryl-2-aminopyrimidine macrocycles and their biol. evaluation against the JAK family of kinase enzymes and FLT3. The most promising leads were assessed for their in vitro ADME properties culminating in the discovery of I, a potent JAK2 (IC50 = 23 and 19 nM for JAK2WT and JAK2V617F, resp.) and FLT3 (IC50 = 22 nM) inhibitor with selectivity against JAK1 and JAK3 (IC50 = 1280 and 520 nM, resp.). Further profiling of I in preclin. species and mouse xenograft and allograft models is described. Compd. I (SB1518) was selected as a development candidate and progressed into clin. trials where it is currently in phase 2 for MF and lymphoma. >> More from SciFinder ®https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXns1ent7c%253D&md5=1fa1a5250cae6ec8c59db67e593fb1f617 Sun Pharma announces US FDA filing acceptance of new drug application (NDA) for deuruxolitinib. News release, Sun Pharma. Oct 6, 2023. https://sunpharma.com/wp-content/uploads/2023/10/Sun-Pharma-Announces-US-FDA-Filing-Acceptance-for-Deuruxolitnib.pdf ( accessed Sept 24, 2024).Google ScholarThere is no corresponding record for this reference.18Chang, J. 4′-Modified Nucleosides for Antiviral Drug Discovery: Achievements and Perspectives. Acc. Chem. Res. 2022, 55 (4), 565– 578, DOI: 10.1021/acs.accounts.1c00697 Google ScholarThere is no corresponding record for this reference.19Weaver, D. F. Chemists Invent Drugs and Drugs Save Lives. ChemMedChem 2024, 19 (12), e202400074 DOI: 10.1002/cmdc.202400074 Google ScholarThere is no corresponding record for this reference.20Lombardino, J. G.; Lowe, J. A., 3rd. The role of the medicinal chemist in drug discovery--then and now. Nat. Rev. Drug Discovery 2004, 3 (10), 853– 862, DOI: 10.1038/nrd1523 Google ScholarThere is no corresponding record for this reference.21Pennington, L. D. Total Synthesis as Training for Medicinal Chemistry. ACS Med. Chem. Lett. 2024, 15 (2), 156– 158, DOI: 10.1021/acsmedchemlett.3c00556 Google ScholarThere is no corresponding record for this reference.22Ma, C.; Chang, J.; Yu, B. Sunlenca®(Lenacapavir): a first-in-class, long-acting HIV-1 capsid inhibitor for treating highly multidrug-resistant HIV-1 infection. Acta Pharm. Sin B 2024, DOI: 10.1016/j.apsb.2024.08.009 Google ScholarThere is no corresponding record for this reference.23Pennington, L. D.; Hesse, M. J.; Koester, D. C.; McAtee, R. C.; Qunies, A. M.; Hu, D. X. Property-Based Drug Design Merits a Nobel Prize. J. Med. Chem. 2024, 67 (14), 11452– 11458, DOI: 10.1021/acs.jmedchem.4c01345 Google ScholarThere is no corresponding record for this reference.24Liang, G. Q.; Deng, J.; Wu, C. X.; Li, W. J.; Hu, Y. F.; Song, Y. Q.; Yin, X. C.; He, Q.; Xiao, Y. C.; Li, G. B. Design, Synthesis, and Biological Evaluation of Boron-Containing β-Lactamase Inhibitors: Closed-Loop Education Experiences in an Undergraduate Medicinal Chemistry Course. J. Chem. Educ. 2023, 100 (2), 803– 810, DOI: 10.1021/acs.jchemed.2c00692 Google Scholar24Design, Synthesis and Biological Evaluation of Boron-Containing β-Lactamase Inhibitors: Closed-loop Education Experiences in an Undergraduate Medicinal Chemistry CourseLiang, Guo-Qing; Deng, Ji; Wu, Cheng-Xu; Li, Wen-Jing; Hu, Yu-Fei; Song, Yu-Qian; Yin, Xiao-Chen; He, Qin; Xiao, You-Cai; Li, Guo-BoJournal of Chemical Education (2023), 100 (2), 803-810CODEN: JCEDA8; ISSN:0021-9584. (American Chemical Society and Division of Chemical Education, Inc.) Medicinal chem. is an integrated discipline that primarily concerns the design, discovery, synthesis, identification and interpretation of biol. active compds. at the mol. level. To assist undergraduates in understanding the core subjects of medicinal chem., we introduced a closed-loop education mode combining fundamentals of theor. and exptl. aspects in an undergraduate medicinal chem. exptl. course.