Roman C. Sarott, Inchul You, Yen-Der Li, Sean T. Toenjes, Katherine A. Donovan, Pooreum Seo, Martha Ordonez, Woong Sub Byun, Muhammad Murtaza Hassan, Franziska Wachter, Edward T. Chouchani, Mikołaj Słabicki, Eric S. Fischer, Benjamin L. Ebert, Stephen M. Hinshaw, and Nathanael S. GrayDOI: 10.1021/jacs.3c06622
Tuesday, October 3, 2023
Monday, October 2, 2023
Tuesday, September 19, 2023
Wednesday, September 13, 2023
Leonard Barasa, Sauradip Chaudhuri, Jeffrey Y. Zhou, Zhaozhao Jiang, Shruti Choudhary, Robert Madison Green, Elenore Wiggin, Michael Cameron, Fiachra Humphries, Katherine A. Fitzgerald, and Paul R. Thompson
Journal of the American Chemical Society 2023
Saturday, September 9, 2023
Mengmeng Zheng and Jianmin Gao
ACS Chemical Biology 2023
Structure-Based Optimization of Covalent, Small-Molecule Stabilizers of the 14-3-3σ/ERα Protein–Protein Interaction from Nonselective Fragments
Markella Konstantinidou, Emira J. Visser, Edmee Vandenboorn, Sheng Chen, Priyadarshini Jaishankar, Maurits Overmans, Shubhankar Dutta, R. Jeffrey Neitz, Adam R. Renslo, Christian Ottmann, Luc Brunsveld, and Michelle R. Arkin
Journal of the American Chemical Society 2023
The stabilization of protein–protein interactions (PPIs) has emerged as a promising strategy in chemical biology and drug discovery. The identification of suitable starting points for stabilizing native PPIs and their subsequent elaboration into selective and potent molecular glues lacks structure-guided optimization strategies. We have previously identified a disulfide fragment that stabilized the hub protein 14-3-3σ bound to several of its clients, including ERα and C-RAF. Here, we show the structure-based optimization of the nonselective fragment toward selective and highly potent small-molecule stabilizers of the 14-3-3σ/ERα complex. The more elaborated molecular glues, for example, show no stabilization of 14-3-3σ/C-RAF up to 150 μM compound. Orthogonal biophysical assays, including mass spectrometry and fluorescence anisotropy, were used to establish structure–activity relationships. The binding modes of 37 compounds were elucidated with X-ray crystallography, which further assisted the concomitant structure-guided optimization. By targeting specific amino acids in the 14-3-3σ/ERα interface and locking the conformation with a spirocycle, the optimized covalent stabilizer 181 achieved potency, cooperativity, and selectivity similar to the natural product Fusicoccin-A. This case study showcases the value of addressing the structure, kinetics, and cooperativity for molecular glue development.
Thursday, September 7, 2023
Srinivasa P. S. Rao et al.
Science 2023, 380, 1349-1356
Sunday, September 3, 2023
Discovery of AZD4747, a Potent and Selective Inhibitor of Mutant GTPase KRASG12C with Demonstrable CNS Penetration
The glycine to cysteine mutation at codon 12 of Kirsten rat sarcoma (KRAS) represents an Achilles heel that has now rendered this important GTPase druggable. Herein, we report our structure-based drug design approach that led to the identification of 14, AZD4747, a clinical development candidate for the treatment of KRASG12C-positive tumors, including the treatment of central nervous system (CNS) metastases. Building on our earlier discovery of C5-tethered quinazoline AZD4625, excision of a usually critical pyrimidine ring yielded a weak but brain-penetrant start point which was optimized for potency and DMPK. Key design principles and measured parameters that give high confidence in CNS exposure are discussed. During optimization, divergence between rodent and non-rodent species was observed in CNS exposure, with primate PET studies ultimately giving high confidence in the expected translation to patients. AZD4747 is a highly potent and selective inhibitor of KRASG12C with an anticipated low clearance and high oral bioavailability profile in humans.
Saturday, September 2, 2023
Pasquale A. Morese, Nahoum Anthony, Michael Bodnarchuk, Claire Jennings, Mathew P. Martin, Richard A. Noble, Nicole Phillips, Huw D. Thomas, Lan Z. Wang, Andrew Lister, Martin E. M. Noble, Richard A. Ward, Stephen R. Wedge, Hannah L. Stewart, and Michael J. WaringDOI: 10.1021/acs.jmedchem.3c00845
A major drawback of cytotoxic chemotherapy is the lack of selectivity toward noncancerous cells. The targeted delivery of cytotoxic drugs to tumor cells is a longstanding goal in cancer research. We proposed that covalent inhibitors could be adapted to deliver cytotoxic agents, conjugated to the β-position of the Michael acceptor, via an addition–elimination mechanism promoted by covalent binding. Studies on model systems showed that conjugated 5-fluorouracil (5FU) could be released upon thiol addition in relevant time scales. A series of covalent epidermal growth factor receptor (EGFR) inhibitors were synthesized as their 5FU derivatives. Achieving the desired release of 5FU was demonstrated to depend on the electronics and geometry of the compounds. Mass spectrometry and NMR studies demonstrated an anilinoquinazoline acrylate ester conjugate bound to EGFR with the release of 5FU. This work establishes that acrylates can be used to release conjugated molecules upon covalent binding to proteins and could be used to develop targeted therapeutics.
Thursday, August 31, 2023
Development of a covalent cereblon-based PROTAC employing a fluorosulfate warhead [@LynJonesChemBio, @RPNowak]
Many cereblon (CRBN) ligands have been used to develop proteolysis targeting chimeras (PROTACs), but all are reversible binders of the E3 ubiquitin ligase. We recently described the use of sulfonyl exchange chemistry to design binders that covalently engage histidine 353 in CRBN for the first time. Here we show that covalent CRBN ligands can be used to develop efficient PROTAC degraders. We demonstrate that the fluorosulfate PROTAC FS-ARV-825 covalently labels CRBN in vitro, and in cells the BRD4 degrader is insensitive to wash-out and competition by potent reversible CRBN ligands, reflecting enhanced pharmacodynamics. We anticipate that covalent CRBN-based PROTACs will enhance degradation efficiencies, thus expanding the scope of addressable targets using the heterobifunctional degrader modality.
Tuesday, August 29, 2023
A covalent inhibitor of the YAP–TEAD transcriptional complex identified by high-throughput screening
Kayla Nutsch, Lirui Song, Emily Chen, Mitchell Hull, Arnab K. Chatterjee, Jian Jeffery Chen and Michael J. Bollong
RSC Chem. Biol., 2023
Yes-associated protein (YAP), the master transcriptional effector downstream of the Hippo pathway, regulates essential cell growth and regenerative processes in animals. However, the activation of YAP observed in cancers drives cellular proliferation, metastasis, chemoresistance, and immune suppression, making it of key interest in developing precision therapeutics for oncology. As such, pharmacological inhibition of YAP by targeting its essential co-regulators, TEA domain transcription factors (TEADs) would likely promote tumor clearance in sensitive tumor types. From a fluorescence polarization-based high throughput screen of over 800 000 diverse small molecules, here we report the identification of a pyrazolopyrimidine-based scaffold that inhibits association of YAP and TEADs. Medicinal chemistry-based optimization identified mCMY020, a potent, covalent inhibitor of TEAD transcriptional activity that occupies a conserved, central palmitoylation site on TEADs.
Thursday, August 24, 2023
Lara Ibrahim, Caroline Stanton, Kayla Nutsch, Thu Nguyen, Chloris Li-Ma, Yeonjin Ko, Gabriel C. Lander, R. Luke Wiseman, Michael J. Bollong
Cell Chemical Biology, 2023
Monday, August 14, 2023
Heta S Desai, Samuel Ofori, Lisa M Boatner, Fengchao Yu, Miranda Villaneuva, Nicholas Ung, Alexey Nesvizhskii, Keriann M Backus
Cancer genomes are rife with genetic variants; one key outcome of this variation is gain-of-cysteine, which is the most frequently acquired amino acid due to missense variants in COSMIC. Acquired cysteines are both driver mutations and sites targeted by precision therapies. However, despite their ubiquity, nearly all acquired cysteines remain uncharacterized. Here, we pair cysteine chemoproteomics, a technique that enables proteome-wide pinpointing of functional, redox sensitive, and potentially druggable residues, with genomics to reveal the hidden landscape of cysteine acquisition. For both cancer and healthy genomes, we find that cysteine acquisition is a ubiquitous consequence of genetic variation that is further elevated in the context of decreased DNA repair. Our chemoproteogenomics platform integrates chemoproteomic, whole exome, and RNA-seq data, with a customized 2-stage false discovery rate (FDR) error controlled proteomic search, further enhanced with a user-friendly FragPipe interface. Integration of CADD predictions of deleteriousness revealed marked enrichment for likely damaging variants that result in acquisition of cysteine. By deploying chemoproteogenomics across 11 cell lines, we identify 116 gain-of-cysteines, of which 10 were liganded by electrophilic druglike molecules. Reference cysteines proximal to missense variants were also found to be pervasive, 791 in total, supporting heretofore untapped opportunities for proteoform-specific chemical probe development campaigns. As chemoproteogenomics is further distinguished by sample-matched combinatorial variant databases and compatible with redox proteomics and small molecule screening, we expect widespread utility in guiding proteoform-specific biology and therapeutic discovery.
Tuesday, August 8, 2023
Simultaneous Covalent Modification of K-Ras(G12D) and K-Ras(G12C) with Tunable Oxirane Electrophiles
Owing to their remarkable pharmaceutical properties compared to those of noncovalent inhibitors, the development of targeted covalent inhibitors (TCIs) has emerged as a powerful method for cancer treatment. The K-Ras mutant, which is prevalent in multiple cancers, has been confirmed to be a crucial drug target in the treatment of various malignancies. However, although the K-Ras(G12D) mutation is present in up to 33% of K-Ras mutations, no covalent inhibitors targeting K-Ras(G12D) have been developed to date. The relatively weak nucleophilicity of the acquired aspartic acid (12D) residue in K-Ras may be the reason for this. Herein, we present the first compound capable of covalently engaging both K-Ras(G12D) and K-Ras(G12C) mutants. Proteome profiling revealed that this compound effectively conjugates with G12C and G12D residues, modulating the protein functions in situ. These findings offer a unique pathway for the development of novel dual covalent inhibitors.
Tuesday, August 1, 2023
Structural and functional fine mapping of cysteines in mammalian glutaredoxin reveal their differential oxidation susceptibility
Corteselli, E.M., Sharafi, M., Hondal, R. et al.
Nat Commun 14, 4550 (2023).
Protein-S-glutathionylation is a post-translational modification involving the conjugation of glutathione to protein thiols, which can modulate the activity and structure of key cellular proteins. Glutaredoxins (GLRX) are oxidoreductases that regulate this process by performing deglutathionylation. However, GLRX has five cysteines that are potentially vulnerable to oxidative modification, which is associated with GLRX aggregation and loss of activity. To date, GLRX cysteines that are oxidatively modified and their relative susceptibilities remain unknown. We utilized molecular modeling approaches, activity assays using recombinant GLRX, coupled with site-directed mutagenesis of each cysteine both individually and in combination to address the oxidizibility of GLRX cysteines. These approaches reveal that C8 and C83 are targets for S-glutathionylation and oxidation by hydrogen peroxide in vitro. In silico modeling and experimental validation confirm a prominent role of C8 for dimer formation and aggregation. Lastly, combinatorial mutation of C8, C26, and C83 results in increased activity of GLRX and resistance to oxidative inactivation and aggregation. Results from these integrated computational and experimental studies provide insights into the relative oxidizability of GLRX’s cysteines and have implications for the use of GLRX as a therapeutic in settings of dysregulated protein glutathionylation.
Tuesday, July 25, 2023
Thomas, A.; Serafini, M.; Grant, E.; Coombs, E.; Bluck, J.; Schiedel, M.; McDonough, M.; Reynolds, J.; Lee, B.; Platt, M.; Sharlandjieva, V.; Biggin, P.; Duarte, F.; Milne, T.; Bush, J.; Conway, S.
Target validation remains a challenge in drug discovery, which leads to a high attrition rate in the drug discovery process, particularly in Phase II clinical trials. Consequently, new approaches to enhance target validation are valuable tools to improve the drug discovery process. Here we report the combination of site-directed mutagenesis and electrophilic fragments to enable the rapid identification of small molecules that selectively inhibit the mutant protein. Using the bromodomain- containing protein BRD4 as an example, we employed a structure-based approach to identify the L94C mutation in the first bromodomain of BRD4 [BRD4(1)] as having minimal effect on BRD4(1) function. We then screen a focused, KAc mimic-containing fragment set, and a diverse fragment library against the mutant and wild-type proteins, and identified a series of fragments that showed high selectivity for the mutant protein. These compounds were elaborated to include an alkyne click tag to enable the attachment of a fluorescent dye. These clickable compounds were then assessed in HEK293T cells, transiently expressing BRD4(1)WT or BRD4(1)L94C, to determine their selectivity for BRD4(1)L94C over other possible cellular targets. One compound was identified that shows very high selectivity for BRD4(1)L94C over all other proteins. This work provides proof-of-concept that the combination of site-directed mutagenesis and electrophilic fragments, in a mutant and conjugate approach, can enable rapid identification of small molecule inhibitors for an appropriately mutated protein of interest. This technology can be used to assess the cellular phenotype of inhibiting the protein of interest, and the electrophilic ligand provides a starting point for non-covalent ligand development.
Friday, July 21, 2023
Tuesday, July 18, 2023
Proteome-wide structural analysis identifies warhead-and coverage-specific biases in cysteine-focused chemoproteomics
Matthew E H White, Jesús Gil, Edward W Tate
Covalent drug discovery has undergone a resurgence over the past two decades and reactive cysteine profiling has emerged in parallel as a platform for ligand discovery through on- and off-target profiling; however, the scope of this approach has not been fully explored at the whole-proteome level. We combined AlphaFold2-predicted side-chain accessibilities for >95% of the human proteome with a meta-analysis of eighteen public cysteine profiling datasets, totaling 44,187 unique cysteine residues, revealing accessibility biases in sampled cysteines primarily dictated by warhead chemistry. Analysis of >3.5 million cysteine-fragment interactions further showed that hit elaboration and optimization drives increased bias against buried cysteine residues. Based on these data, we suggest that current profiling approaches cover a small proportion of potential ligandable cysteine residues and propose future directions for increasing coverage, focusing on high-priority residues and depth. All analysis and produced resources are freely available and extendable to other reactive amino acids.
Monday, July 17, 2023
Ying Chen, Gregory B. Craven, Roarke A. Kamber, Adolfo Cuesta, Serhii Zhersh, Yurii S. Moroz, Michael C. Bassik & Jack Taunton
Nature Chemistry 2023
Advances in chemoproteomic technology have revealed covalent interactions between small molecules and protein nucleophiles, primarily cysteine, on a proteome-wide scale. Most chemoproteomic screening approaches are indirect, relying on competition between electrophilic fragments and a minimalist electrophilic probe with inherently limited proteome coverage. Here we develop a chemoproteomic platform for direct electrophile-site identification based on enantiomeric pairs of clickable arylsulfonyl fluoride probes. Using stereoselective site modification as a proxy for ligandability in intact cells, we identify 634 tyrosines and lysines within functionally diverse protein sites, liganded by structurally diverse probes. Among multiple validated sites, we discover a chiral probe that modifies Y228 in the MYC binding site of the epigenetic regulator WDR5, as revealed by a high-resolution crystal structure. A distinct chiral probe stimulates tumour cell phagocytosis by covalently modifying Y387 in the recently discovered immuno-oncology target APMAP. Our work provides a deep resource of ligandable tyrosines and lysines for the development of covalent chemical probes.
Saturday, July 8, 2023
N-Acryloylindole-alkyne (NAIA) enables imaging and profiling new ligandable cysteines and oxidized thiols by chemoproteomics
Nat Commun 14, 3564 (2023).
Cysteine has been exploited as the binding site of covalent drugs. Its high sensitivity to oxidation is also important for regulating cellular processes. To identify new ligandable cysteines which can be hotspots for therapy and to better study cysteine oxidations, we develop cysteine-reactive probes, N-acryloylindole-alkynes (NAIAs), which have superior cysteine reactivity owing to delocalization of π electrons of the acrylamide warhead over the whole indole scaffold. This allows NAIAs to probe functional cysteines more effectively than conventional iodoacetamide-alkyne, and to image oxidized thiols by confocal fluorescence microscopy. In mass spectrometry experiments, NAIAs successfully capture new oxidized cysteines, as well as a new pool of ligandable cysteines and proteins. Competitive activity-based protein profiling experiments further demonstrate the ability of NAIA to discover lead compounds targeting these cysteines and proteins. We show the development of NAIAs with activated acrylamide for advancing proteome-wide profiling and imaging ligandable cysteines and oxidized thiols.
Thursday, July 6, 2023
Expanding the Chemistry of Dihaloacetamides as Tunable Electrophiles for Reversible Covalent Targeting of Cysteines
Daiki Yamane, Ryo Tetsukawa, Naoki Zenmyo, Kaori Tabata, Yuya Yoshida, Naoya Matsunaga, Naoya Shindo, and Akio OjidaDOI: 10.1021/acs.jmedchem.3c00737
Sunday, June 25, 2023
Grob, N. M.; Remarcik, C.; Rössler, S. L.; Wong, J. Y. K.; Wang, J. C. K.; Tao, J.; Smith, C. L.; Loas, A.; Buchwald, S. L.; Eaton, D. L.; Preciado López, M.; Pentelute, B. L.
Protein–protein interactions (PPIs) are intriguing targets in drug discovery and development. Peptides are well suited to target PPIs, which typically present with large surface areas lacking distinct features and deep binding pockets. To improve binding interactions to these topologies by PPI-focused therapeutics and advance their development, potential ligands can be equipped with electrophilic groups to enable binding through covalent mechanisms of action. We report a strategy termed electrophile scanning to identify reactivity hotspots in a known peptide ligand. Cysteine mutants of the ligand are used to install protein-reactive modifiers via a palladium oxidative addition complex (Pd-OAC). Reactivity hotspots are revealed by cross-linking reactions with the target protein under physiological conditions. In a system with the 9-mer peptide antigen VL9 and MHC class I receptor HLA-E, we identify two reactivity hotspots that afford up to 87% conversion to the protein–peptide conjugate within 4 hours. The reactions are specific to the target protein in vitro and dependent on the peptide sequence. Moreover, the cross-linked peptide successfully inhibits molecular recognition of HLA-E by CD94─NKG2A possibly due to structural changes enacted at the PPI interface. The results illustrate the potential of electrophile scanning as a tool for rapid discovery and development of covalent peptide binders.
Alex E. Crolais, Neil D. Dolinski, Nicholas R. Boynton, Julia M. Radhakrishnan, Scott A. Snyder, and Stuart J. Rowan
Journal of the American Chemical Society 2023
Tuesday, June 6, 2023
Cravatt, B.; Njomen, E.; Hayward, R.; DeMeester, K.; Ogasawara, D.; Dix, M.; Nguyen, T.; Ashby, P.; Simon, G.; Schreiber, S.; Melillo, B.
Covalent chemistry is a versatile approach for expanding the ligandability of the human proteome. Activity-based protein profiling (ABPP) can infer the specific residues modified by electrophilic compounds through competition with broadly reactive probes. Nonetheless, the extent to which such residue-directed ABPP platforms fully assess the protein targets of electrophilic compounds in human cells remains unclear. Here, we introduce a complementary approach that directly identifies proteins showing stereoselective reactivity with focused libraries of stereochemically-defined, alkynylated electrophilic compounds. Integration of protein- and cysteine-directed ABPP data from compound-treated human cancer cells revealed generally well-correlated target maps and highlighted specific features, such as protein size and the proteotypicity of cysteine-containing peptides, that help to explain gaps in each ABPP platform. The integrated ABPP strategy furnished stereoselective, high-engagement covalent ligands for > 300 structurally and functionally diverse human proteins, including compounds that modulate enzymes by canonical (active-site cysteine) and non-canonical (isotype-restricted and non-catalytic cysteines) mechanisms.
Monday, June 5, 2023
Structure-Based Design and Characterization of the Highly Potent and Selective Covalent Inhibitors Targeting the Lysine Methyltransferases G9a/GLP
Protein lysine methyltransferases G9a and GLP, which catalyze mono- and di-methylation of histone H3K9 and nonhistone proteins, play important roles in diverse cellular processes. Overexpression or dysregulation of G9a and GLP has been identified in various types of cancer. Here, we report the discovery of a highly potent and selective covalent inhibitor 27 of G9a/GLP via the structure-based drug design approach following structure–activity relationship exploration and cellular potency optimization. Mass spectrometry assays and washout experiments confirmed its covalent inhibition mechanism. Compound 27 displayed improved potency in inhibiting the proliferation and colony formation of PANC-1 and MDA-MB-231 cell lines and exhibited enhanced potency in reducing the levels of H3K9me2 in cells compared to noncovalent inhibitor 26. In vivo, 27 showed significant antitumor efficacy in the PANC-1 xenograft model with good safety. These results clearly indicate that 27 is a highly potent and selective covalent inhibitor of G9a/GLP.
Characterization of a Potent and Orally Bioavailable Lys-Covalent Inhibitor of Apoptosis Protein (IAP) Antagonist
Thursday, June 1, 2023
David P. Byun, Jennifer Ritchie, Yejin Jung, Ronald Holewinski, Hong-Rae Kim, Ravichandra Tagirasa, Joseph Ivanic, Claire M. Weekley, Michael W. Parker, Thorkell Andresson, and Euna Yoo
Journal of the American Chemical Society 2023 145 (20), 11097-11109
Strategies to target specific protein cysteines are critical to covalent probe and drug discovery. 3-Bromo-4,5-dihydroisoxazole (BDHI) is a natural product-inspired, synthetically accessible electrophilic moiety that has previously been shown to react with nucleophilic cysteines in the active site of purified enzymes. Here, we define the global cysteine reactivity and selectivity of a set of BDHI-functionalized chemical fragments using competitive chemoproteomic profiling methods. Our study demonstrates that BDHIs capably engage reactive cysteine residues in the human proteome and the selectivity landscape of cysteines liganded by BDHI is distinct from that of haloacetamide electrophiles. Given its tempered reactivity, BDHIs showed restricted, selective engagement with proteins driven by interactions between a tunable binding element and the complementary protein sites. We validate that BDHI forms covalent conjugates with glutathione S-transferase Pi (GSTP1) and peptidyl-prolyl cis–trans isomerase NIMA-interacting 1 (PIN1), emerging anticancer targets. BDHI electrophile was further exploited in Bruton’s tyrosine kinase (BTK) inhibitor design using a single-step late-stage installation of the warhead onto acrylamide-containing compounds. Together, this study expands the spectrum of optimizable chemical tools for covalent ligand discovery and highlights the utility of 3-bromo-4,5-dihydroisoxazole as a cysteine-reactive electrophile.
Monday, May 29, 2023
Fu, L., Jung, Y., Tian, C. et al.
Nat Chem Biol (2023).
With an eye toward expanding chemistries used for covalent ligand discovery, we elaborated an umpolung strategy that exploits the ‘polarity reversal’ of sulfur when cysteine is oxidized to sulfenic acid, a widespread post-translational modification, for selective bioconjugation with C-nucleophiles. Here we present a global map of a human sulfenome that is susceptible to covalent modification by members of a nucleophilic fragment library. More than 500 liganded sulfenic acids were identified on proteins across diverse functional classes, and, of these, more than 80% were not targeted by electrophilic fragment analogs. We further show that members of our nucleophilic fragment library can impair functional protein–protein interactions involved in nuclear oncoprotein transport and DNA damage repair. Our findings reveal a vast expanse of ligandable sulfenic acids in the human proteome and highlight the utility of nucleophilic small molecules in the fragment-based covalent ligand discovery pipeline, presaging further opportunities using non-traditional chemistries for targeting proteins.
Sunday, May 28, 2023
Wednesday, May 24, 2023
Burns, A.R., Baker, R.J., Kitner, M. et al. Selective control of parasitic nematodes using bioactivated nematicides.
Parasitic nematodes are a major threat to global food security, particularly as the world amasses 10 billion people amid limited arable land. Most traditional nematicides have been banned owing to poor nematode selectivity, leaving farmers with inadequate means of pest control. Here we use the model nematode Caenorhabditis elegans to identify a family of selective imidazothiazole nematicides, called selectivins, that undergo cytochrome-p450-mediated bioactivation in nematodes. At low parts-per-million concentrations, selectivins perform comparably well with commercial nematicides to control root infection by Meloidogyne incognita, a highly destructive plant-parasitic nematode. Tests against numerous phylogenetically diverse non-target systems demonstrate that selectivins are more nematode-selective than most marketed nematicides. Selectivins are first-in-class bioactivated nematode controls that provide efficacy and nematode selectivity.
Roman C. Sarott, Inchul You, Yen-Der Li, Sean T. Toenjes, Katherine A. Donovan, Pooreum Seo, Martha Ordonez, Woong Sub Byun, Muhammad Murtaz...
Jian Ding, Guo Li, Hejun Liu, Lulu Liu, Ying Lin, Jingyan Gao, Guoqiang Zhou, Lingling Shen, Mengxi Zhao, Yanyan Yu, Weihui Guo, Ulrich Homm...
Ethan S Toriki, James W Papatzimas, Kaila Nishikawa, Dustin Dovala, Lynn M McGregor, Matthew J Hesse, Jeffrey M McKenna, John A Tallarico, M...
Mapping the chemical space of active-site targeted covalent ligands for protein tyrosine phosphatasesHong, S. ho; Xi, S. Y.; Johns, A. C.; Tang, L. C.; Li, A.; Jovanovic, M.; Shah, N. H. ChemRxiv 2022 . https://doi.org/10.26434/chemrxiv-2...