Current research in chemical biology最新文献

{"title":"XNA enzymes by evolution and design","authors":"Turnee N. Malik ,&nbsp;John C. Chaput","doi":"10.1016/j.crchbi.2021.100012","DOIUrl":"10.1016/j.crchbi.2021.100012","url":null,"abstract":"<div><p>The last decade has witnessed tremendous growth in the field of synthetic genetics, an area of synthetic biology that applies concepts that are commonly associated with the field of genetics, such as heredity and evolution, to artificial genetic polymers with novel backbone structures (XNAs). In addition to the emergence of biologically stable affinity reagents (aptamers), progress in this area has led to the discovery of XNA enzymes (XNAzymes) that are capable of mediating transphosphorylation chemistry with multiple turnover activity. This review explores the evolution and rational design of XNAzymes as well as their potential as reagents in biomedical applications.</p></div>","PeriodicalId":72747,"journal":{"name":"Current research in chemical biology","volume":"1 ","pages":"Article 100012"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666246921000124/pdfft?md5=2f1ec95fffd0528264b1aa90dca4db65&pid=1-s2.0-S2666246921000124-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44946582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Removal of ammonia and nitrates from contaminated water by using solid waste bio-adsorbents","authors":"S. Dey,&nbsp;N. Haripavan,&nbsp;S.R. Basha,&nbsp;G.V. Babu","doi":"10.1016/j.crchbi.2021.100005","DOIUrl":"https://doi.org/10.1016/j.crchbi.2021.100005","url":null,"abstract":"<div><p>The presence of pollutants in aqueous solution mainly from hazardous heavy metals and metalloids is creating an environmental and social problem. The ammonia and nitrates are one of the major groundwater contaminants present in the rural areas. A nitrate was regulated in drinking water quality mainly due to excess amounts can cause methemoglobinemia disease. Ammonia in both gaseous and liquid form can be irritating to the eyes, respiratory tract failure and skin due to its alkaline nature. The biological effects of ammonia and nitrates in humans after acute exposures are dose-related depend on their concentration; the amount is taken by the body and duration of exposure. Biosorption is a physiochemical process that occurs naturally in certain biomass which allows it to passively concentrate and bind contaminants onto its cellular structure. It is metabolically passive process not require energy and amount of contaminants in sorbent can remove is dependent on kinetic equilibrium and composition of the sorbents at cellular surface. Every biosorbent had different physical, chemical and biological properties for heavy metals removal by biosorption from the water. The oxygen functional groups are very important characteristics of biosorbents because they measured the surface properties and hence their quality as biosorbents. The analysis of isotherm data by fitting them to different models is important to find a sustainable model that can be used. From the biosorption isotherms describe how the sorbate molecules are distributed between the liquid phase and solid phase when the system reaches equilibrium. The process can be made economical by regenerating and reusing of biosorbent after removing the metals. Various bioreactors can be used in biosorption for the removal of metal ions from large volume of water.</p></div>","PeriodicalId":72747,"journal":{"name":"Current research in chemical biology","volume":"1 ","pages":"Article 100005"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.crchbi.2021.100005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91594435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Translating PROTAC chemical series optimization into functional outcomes underlying BRD7 and BRD9 protein degradation","authors":"Kristin M. Riching ,&nbsp;James D. Vasta ,&nbsp;Scott J. Hughes ,&nbsp;Vittoria Zoppi ,&nbsp;Chiara Maniaci ,&nbsp;Andrea Testa ,&nbsp;Marjeta Urh ,&nbsp;Alessio Ciulli ,&nbsp;Danette L. Daniels","doi":"10.1016/j.crchbi.2021.100009","DOIUrl":"10.1016/j.crchbi.2021.100009","url":null,"abstract":"<div><p>Proteolysis targeting chimeras (PROTACs) are complex molecules to design and optimize as degraders, primarily because the linker that bridges the two binding ligands is a highly variable element of design, yet critical for simultaneous engagement of target and E3 ligase into a ternary complex, target ubiquitination and ultimately degradation. These chemical and mechanistic complexities mean that the PROTAC design process can be a daunting endeavour, and it remains unpredictable how to best optimize them into high-quality degraders. To understand how medicinal chemistry decisions could translate into functional outcomes, here we present a retrospective and holistic mechanistic study of a two-part sequential medicinal chemistry program, termed Series 1 and 2, which previously led to the discovery of VZ185, a potent VHL-based dual BRD7 and BRD9 degrader. Analysis of the initial Series 1 compounds across three different cell lines containing endogenously tagged CRISPR HiBiT BRD7 or BRD9 revealed only partial degradation of BRD9, and no degradation of BRD7. Analysis of Series 2 PROTACs, which was designed based on the degradation outcomes of Series 1 and in the absence of ternary complex structural information, showed the emergence of three lead compounds improved in BRD9 degradation and with additional specificity for BRD7. Biochemical analysis to interrogate ternary complex affinity and cooperativity demonstrated how subtle chemistry alterations impacted these parameters both positively and negatively, though on average, achieving only minor improvements in Series 2. In contrast, the greatest change between Series 1 and 2 was an improvement in cellular permeability, with the three lead degradation compounds showing high permeability. Lastly, cellular ubiquitination studies were performed and demonstrated the most potent degrader, VZ185, was the most robust for ubiquitination despite neither being the most permeable nor the best at forming ternary complex within the entire set. VZ185 and similarly active compounds were found to be efficacious degraders across all cell lines tested. Our mechanistic characterization provides insights that, while our structurally unguided medicinal chemistry campaign improved most notably cell permeability, increased degradation outcomes also required retaining productive ternary complex formation and target ubiquitination.</p></div>","PeriodicalId":72747,"journal":{"name":"Current research in chemical biology","volume":"1 ","pages":"Article 100009"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666246921000094/pdfft?md5=23838ac8e2c7ecabc0fa537e0fd41d9f&pid=1-s2.0-S2666246921000094-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49132347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metalloenzyme mechanisms correlated to their turnover number and metal lability","authors":"Caio B. Castro,&nbsp;Millena P. Ferreira,&nbsp;Caterina G.C. Marques Netto","doi":"10.1016/j.crchbi.2021.100004","DOIUrl":"https://doi.org/10.1016/j.crchbi.2021.100004","url":null,"abstract":"<div><p>Metalloenzymes are involved in several different reactions and the metal can display distinct roles, such as redox chemistry or substrate activation. The activation mechanism is mainly described to occur by bond polarization upon coordination to the metal center. However, the disregard of the outer sphere mechanism can have a profound impact on the mechanism proposition of reactions. In the outer sphere coordination, the metal acts as an electrostatic activator in its hydrated form. Since hydration is crucial in this mechanism, metal lability is related to the proposition of an enzyme mechanism. In this review, we will evidence the impact of metal lability in the design of metalloenzyme mechanisms from EC 1–6, correlating some of the enzymes to their biomimetic compounds.</p></div>","PeriodicalId":72747,"journal":{"name":"Current research in chemical biology","volume":"1 ","pages":"Article 100004"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.crchbi.2021.100004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91594436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Untangling the bioactive properties of therapeutic deep eutectic solvents based on natural terpenes","authors":"Eduardo Silva ,&nbsp;Filipe Oliveira ,&nbsp;Joana M. Silva ,&nbsp;Rui L. Reis ,&nbsp;Ana Rita C. Duarte","doi":"10.1016/j.crchbi.2021.100003","DOIUrl":"10.1016/j.crchbi.2021.100003","url":null,"abstract":"<div><p>Treatment of microbial-related infections remains a clinical challenge that has been slowly aggravating over recent years, due to the dissemination of resistance against currently applied treatment protocols. In this current scenario, the design of novel treatment approaches is of great importance, being a prominent focus of the scientific community. In recent years deep eutectic systems (DES) have gained the attention of the scientific community due to their remarkable physicochemical and biological properties, versatility, and compliance with the green chemistry metrics. In this work, DES containing a monoterpenoid (thymol (THY) and menthol (ME)) in combination with ibuprofen (IBU) were formulated and characterized via thermal analyses and NMR spectroscopy. The biological activity of the most promising formulations was then explored, with focus on its antimicrobial and anticancer activity. Both ME and THY-based formulations presented relevant antibacterial activity against the panel of microorganisms tested. Among the THY-based formulation tested, THY:IBU 3:1 M ratio, showed the highest antibacterial activity, affecting all tested microorganisms, while ME:IBU 3:1 M ratio was only effective against Gram-positive bacteria and <em>Candida albicans</em>. Furthermore, both ME and THY-based formulations revealed cytotoxic effect towards the cancer cell model used (HT29), where ME:IBU 3:1 stood out as the most selective towards cancer cells without compromising normal cells viability. Overall, the results obtained highlight the potential use of terpene-based THEDES formulations that, due to their enhanced thermal properties, may represent a versatile alternative in several biomedical applications where an effective antimicrobial or anticancer therapeutic action remains a challenge.</p></div>","PeriodicalId":72747,"journal":{"name":"Current research in chemical biology","volume":"1 ","pages":"Article 100003"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.crchbi.2021.100003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"102537562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Benefits and pitfalls: Epigenetic modulators in prostate cancer intervention","authors":"Neha Upadhyay ,&nbsp;Kalpana Tilekar ,&nbsp;Jessica D. Hess ,&nbsp;Vadim S. Pokrovsky ,&nbsp;Renato J. Aguilera ,&nbsp;Ramaa C S","doi":"10.1016/j.crchbi.2021.100006","DOIUrl":"10.1016/j.crchbi.2021.100006","url":null,"abstract":"<div><p>Prostate cancer is a common malignancy in men worldwide. In the initial treatment, ADT has been used as the cornerstone, but unfortunately, mainstream patients transition to the refractory state of prostate cancer, i.e., CRPC. Thus, newer therapeutics are required for the treatment of patients un or less responsive to ADT. Epigenetic aberrations, namely, DNA methylation and histone modifications are the ultimate chauffeurs of prostate cancer with an emerging role to erase the roadmaps to this disease. However, more robust clinical evidence would be indispensable to put forward reliable therapeutics with the scope to effectively combat this disease. In this review, we have described the present status of epigenetic biomarkers and their clinical impacts on prostate cancer. We have also comprehensively deliberated the role of different epigenetic master regulators involved in the management of disease, appropriate treatment landscape, and the recent preclinical and ongoing clinical evaluations in prostate adenocarcinoma.</p></div>","PeriodicalId":72747,"journal":{"name":"Current research in chemical biology","volume":"1 ","pages":"Article 100006"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.crchbi.2021.100006","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54038649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microwave-assisted extraction and matrix solid-phase dispersion as green analytical chemistry sample preparation techniques for the valorisation of mango processing waste","authors":"Mateus L. Segatto ,&nbsp;Karine Zanotti ,&nbsp;Vânia G. Zuin","doi":"10.1016/j.crchbi.2021.100007","DOIUrl":"10.1016/j.crchbi.2021.100007","url":null,"abstract":"<div><p>Food supply chain waste is consisted not only by the visible part generated in commercial and consumer steps, but also by the residues generated during harvesting and processing of food-related plants. A great part of these materials is unavoidable, meaning that they cannot be prevented trough waste reduction policies currently being pushed to achieve better food distribution and end hunger across the globe. Valorising this waste stream may help increasing stability in the food sector, having not only a financial gain, but also an environmental and social positive impact. Mango Processing Waste (MPW) is one of the examples of how such residues are poorly explored, as its large volumes contain several valuable substances, such as bioactive compounds, that can be used in the food industry as ingredients and as nutraceuticals, pesticides in agriculture, biocides and other uses. The flavonol hyperoside and the xanthone mangiferin are the main secondary metabolites found in MPW, being reported to have biological activities that range from antioxidant to pesticidal and pharmacological potential uses. In a broader context considering the use of MPW in a biorefinery and circular economy concepts, sustainable processes are required to meet future sustainability parameters. Therefore, Microwave-Assisted Extraction (MAE) and Matrix Solid-Phase Dispersion (MPSD), two sample preparation techniques, were discussed and studied as proposed green and sustainable methodologies for the extraction of mangiferin and hyperoside from MPW. Doehlert and Box-Behnken experimental designs were used to help assessing the influences of the variables of each technique, allowing to employ a Response Surface Methodology (RSM) to visualize the best conditions and calculate optimum parameters. Fast extraction was achieved using MAE, which obtained maximum response of 261.39 mg kg⁻¹ of mangiferin and 244.44 mg kg⁻¹ of hyperoside. Higher yields were obtained using MSPD methodology, with an extraction yield of 352.90 mg kg⁻¹ and 398.52 mg kg⁻¹ of mangiferin and hyperoside, respectively. The conditions that allowed maximum simultaneous extraction concentrations were calculated using the desirability function. MAE and MSPD methodologies were compared, with an overall conclusion that both were adequate for the determination of the two analytes and can be further studied to be used in higher scales.</p></div>","PeriodicalId":72747,"journal":{"name":"Current research in chemical biology","volume":"1 ","pages":"Article 100007"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666246921000070/pdfft?md5=1f1906f3275fc872950b7f9f88e759ec&pid=1-s2.0-S2666246921000070-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54038668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of an AchillesTAG degradation system and its application to control CAR-T activity","authors":"Gesine K. Veits ,&nbsp;Christina S. Henderson ,&nbsp;Abigail Vogelaar ,&nbsp;Scott J. Eron ,&nbsp;Linda Lee ,&nbsp;Ashley Hart ,&nbsp;Richard W. Deibler ,&nbsp;Joelle Baddour ,&nbsp;W. Austin Elam ,&nbsp;Roman V. Agafonov ,&nbsp;Jessica Freda ,&nbsp;Prasoon Chaturvedi ,&nbsp;Brendon Ladd ,&nbsp;Mark W. Carlson ,&nbsp;Harit U. Vora ,&nbsp;Thomas G. Scott ,&nbsp;Trang Tieu ,&nbsp;Arushi Jain ,&nbsp;Chi-Li Chen ,&nbsp;Emily S. Kibbler ,&nbsp;Rhamy Zeid","doi":"10.1016/j.crchbi.2021.100010","DOIUrl":"https://doi.org/10.1016/j.crchbi.2021.100010","url":null,"abstract":"<div><p>In addition to the therapeutic applicability of targeted protein degradation (TPD), the modality also harbors unique properties that enable the development of innovative chemical biology tools to interrogate complex biology. TPD offers an all-chemical strategy capable of the potent, durable, selective, reversible, and time-resolved control of the levels of a given target protein in both <em>in vitro</em> and <em>in vivo</em> contexts. These properties are particularly well-suited for enabling the precise perturbation of a given gene to understand its biology, identify dependencies/vulnerabilities in disease contexts, and as a strategy to control gene therapies. To leverage these elegant properties, we developed the AchillesTag (aTAG) degradation system to serve as a tool in target identification and validation efforts. The aTAG degradation system provides a novel degradation tag based on the MTH1 protein paired with three fully validated bifunctional degraders with both <em>in vitro</em> and <em>in vivo</em> applicability. We catalog the development of the aTAG system from selection and validation of the novel MTH1 aTAG, alongside a comprehensive SAR campaign to identify high performing tool degraders. To demonstrate the utility of the aTAG system to dissect a complex biological system, we apply the technology to the control of Chimeric Antigen Receptor (CAR) activity. Using aTAG, we demonstrate the ability to potently and selectively control CAR protein levels, resulting in the exquisite rheostat control of CAR mediated T-cell activity. Furthermore, we showcase the <em>in vivo</em> application of the system via degradation of the aTAG-fused CAR protein in a human xenograft model. The aTAG degradation system provides a complete chemical biology tool to aid foundational target validation efforts that inspire drug discovery campaigns towards therapeutic applicability.</p></div>","PeriodicalId":72747,"journal":{"name":"Current research in chemical biology","volume":"1 ","pages":"Article 100010"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666246921000100/pdfft?md5=10574bda36739773462be7ead17740f1&pid=1-s2.0-S2666246921000100-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91594439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis and structure-activity relationships of targeted protein degraders for the understudied kinase NEK9","authors":"SeongShick Ryu ,&nbsp;Gillian E. Gadbois ,&nbsp;Andrew J. Tao ,&nbsp;Benjamin J. Fram ,&nbsp;Jie Jiang ,&nbsp;Bridget Boyle ,&nbsp;Katherine A. Donovan ,&nbsp;Noah M. Krupnick ,&nbsp;Bethany C. Berry ,&nbsp;Debabrata Bhunia ,&nbsp;Injae Shin ,&nbsp;Eric S. Fischer ,&nbsp;Nathanael S. Gray ,&nbsp;Taebo Sim ,&nbsp;Fleur M. Ferguson","doi":"10.1016/j.crchbi.2021.100008","DOIUrl":"10.1016/j.crchbi.2021.100008","url":null,"abstract":"<div><p>Nek9 is a member of the understudied Nek family of dark kinases. Aberrant activation of Nek9 kinase signaling has been linked to poor keratinocyte differentiation phenotypes, and is a key driver of nevus comedonicus, a rare, localized form of acne. Nek9 also has essential scaffolding roles; during mitosis the non-catalytic C-terminal domain of Nek9 binds to Nek6 and Nek7, releasing them from an auto-inhibitory conformation, and enabling proper mitotic progression. Finally, Nek9 expression has been linked to cancer proliferation. SiRNA mediated Nek9 knock-down in a panel of cancer cell lines induces G1 cell cycle arrest and inhibits proliferation when p53 is also inactivated; cell lines with functional p53 are unaffected. Presently, no selective small molecule Nek9 chemical probes are available, though a subset of promiscuous kinase inhibitors have Nek9 activity. Recently described targeted protein degradation approaches have shown that degrader molecules based on multi-targeted kinase inhibitors may effect selective kinase degradation, despite binding to many targets. In this study we report the identification and SAR of potent degraders of the NEK9 kinase that represent attractive leads for further development. Future work is needed to optimize the selectivity of the compounds.</p></div>","PeriodicalId":72747,"journal":{"name":"Current research in chemical biology","volume":"1 ","pages":"Article 100008"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.crchbi.2021.100008","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"111513857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enabling cancer target validation with genetically encoded systems for ligand-induced protein degradation","authors":"Yuxiang Zhang,&nbsp;Michael A. Erb","doi":"10.1016/j.crchbi.2021.100011","DOIUrl":"10.1016/j.crchbi.2021.100011","url":null,"abstract":"<div><p>Recent technological advances have improved the ability of functional genetic approaches to discover new targets for anti-cancer therapeutics. At the same time, advances in discovery chemistry promise to deliver on an ever-larger fraction of these new targets. However, the fundamental difference in the kinetics of genetic and chemical perturbations can make it difficult to judge the performance of new chemical tools when only genetic information is available. Here, we review a series of genetically encoded, ligand-inducible protein degradation systems that can bridge the gap between genetics and pharmacology. These approaches rely on tagging a protein of interest with a small-molecule-responsive degron that enables conditional protein degradation. Given their rapid effects, these systems can facilitate mechanistic interpretations that are not typically possible using traditional genetic approaches. Therefore, inducible degradation systems can be employed at the earliest stages of target validation to provide mechanistic insights that will better guide future drug discovery efforts.</p></div>","PeriodicalId":72747,"journal":{"name":"Current research in chemical biology","volume":"1 ","pages":"Article 100011"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666246921000112/pdfft?md5=03ae8155b8eabbfa2f16454fd67e7d7b&pid=1-s2.0-S2666246921000112-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44836456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}