Genomes and Genes
small molecule libraries
Summary: Large collections of small molecules (molecular weight about 600 or less), of similar or diverse nature which are used for high-throughput screening analysis of the gene function, protein interaction, cellular processing, biochemical pathways, or other chemical interactions.
Publications111 found, 100 shown here
- Seshadri C, Sedaghat N, Campo M, Peterson G, Wells R, Olson G, et al. Transcriptional networks are associated with resistance to Mycobacterium tuberculosis infection. PLoS ONE. 2017;12:e0175844 pubmed publisher..These data identify a potential cellular mechanism underlying the clinical phenomenon of resistance to M.tb infection despite known exposure to an infectious contact. ..
- Holbeck S, Camalier R, Crowell J, Govindharajulu J, Hollingshead M, Anderson L, et al. The National Cancer Institute ALMANAC: A Comprehensive Screening Resource for the Detection of Anticancer Drug Pairs with Enhanced Therapeutic Activity. Cancer Res. 2017;77:3564-3576 pubmed publisher..i>Cancer Res; 77(13); 3564-76. ©2017 AACR. ..
- Saarbach J, Masi D, Zambaldo C, Winssinger N. Facile access to modified and functionalized PNAs through Ugi-based solid phase oligomerization. Bioorg Med Chem. 2017;25:5171-5177 pubmed publisher..We demonstrate the utility of the method with the synthesis of several bioactive small molecules (a peptide ligand, a kinase inhibitor and a glycan)-PNA conjugates. ..
- Axen S, Huang X, Cáceres E, Gendelev L, Roth B, Keiser M. A Simple Representation of Three-Dimensional Molecular Structure. J Med Chem. 2017;60:7393-7409 pubmed publisher..Finally, we report novel drug-to-target binding predictions inaccessible by 2D fingerprints and confirm three of them experimentally with ligand efficiencies from 0.442-0.637 kcal/mol/heavy atom. ..
- Matossian M, Elliott S, Hoang V, Burks H, Phamduy T, Chrisey D, et al. Novel application of the published kinase inhibitor set to identify therapeutic targets and pathways in triple negative breast cancer subtypes. PLoS ONE. 2017;12:e0177802 pubmed publisher..Future studies will examine specific roles of the kinases in mechanisms responsible for acquisition of the mesenchymal and/or migratory phenotype. ..
- Jin L, Garcia J, Chan E, de la Cruz C, Segal E, Merchant M, et al. Therapeutic Targeting of the CBP/p300 Bromodomain Blocks the Growth of Castration-Resistant Prostate Cancer. Cancer Res. 2017;77:5564-5575 pubmed publisher..Our findings offer a preclinical proof of concept for small-molecule therapies to target the CBP/p300 bromodomain as a strategy to treat castration-resistant prostate cancer. Cancer Res; 77(20); 5564-75. Â©2017 AACR. ..
- Fradera X, Babaoglu K. Overview of Methods and Strategies for Conducting Virtual Small Molecule Screening. Curr Protoc Chem Biol. 2017;9:196-212 pubmed publisher..Subsequently, strategic considerations are presented for choosing a VS method, or a combination of methods, as well as the necessary steps to prepare, run, and analyze a VS campaign. © 2017 by John Wiley & Sons, Inc. ..
- Woo T, Yoon M, Hong S, Choi J, Ha N, Sun H, et al. Anti-cancer effect of novel PAK1 inhibitor via induction of PUMA-mediated cell death and p21-mediated cell cycle arrest. Oncotarget. 2017;8:23690-23701 pubmed publisher..Considering our result, IPP-14 and its derivatives would be possible candidates for PAK1 and p21 induction targeted anti-cancer drug. ..
- Roy B. Potential of small-molecule fungal metabolites in antiviral chemotherapy. Antivir Chem Chemother. 2017;25:20-52 pubmed publisher..This also highlighted the mechanistic details of inhibition of viral replication along with structure-activity relationship of some common and important classes of fungal metabolites. ..
- Bresciani A, Missineo A, Gallo M, Cerretani M, Fezzardi P, Tomei L, et al. Nuclear factor (erythroid-derived 2)-like 2 (NRF2) drug discovery: Biochemical toolbox to develop NRF2 activators by reversible binding of Kelch-like ECH-associated protein 1 (KEAP1). Arch Biochem Biophys. 2017;631:31-41 pubmed publisher
- Kong G, Yu M, Gu Z, Chen Z, Xu R, O Bryant D, et al. Selective small-chemical inhibitors of protein arginine methyltransferase 5 with anti-lung cancer activity. PLoS ONE. 2017;12:e0181601 pubmed publisher..Thus, identified PRMT5-specific small-molecule inhibitors would help elucidate the biological roles of PRMT5 and serve as lead compounds for future drug development. ..
- Schoumacher M, Burbridge M. Key Roles of AXL and MER Receptor Tyrosine Kinases in Resistance to Multiple Anticancer Therapies. Curr Oncol Rep. 2017;19:19 pubmed publisher..One of the major challenges to successful development of these therapies will be the application of robust predictive biomarkers for clear-cut patient stratification. ..
- Appulage D, Schug K. Silica hydride based phases for small molecule separations using automated liquid chromatography-mass spectrometry method development. J Chromatogr A. 2017;1507:115-123 pubmed publisher..The more polar Diol phase still provided good retention in reversed phase mode. Retention and selectivity were all highly reproducible. ..
- Berg A, Berg T. A small-molecule screen identifies the antitrypanosomal agent suramin and analogues NF023 and NF449 as inhibitors of STAT5a/b. Bioorg Med Chem Lett. 2017;27:3349-3352 pubmed publisher..Our data extend the known in vitro targets of suramin and analogues to include members of the STAT protein family. ..
- Massignan T, Sangiovanni V, Biggi S, Stincardini C, Elezgarai S, Maietta G, et al. A Small-Molecule Inhibitor of Prion Replication and Mutant Prion Protein Toxicity. ChemMedChem. 2017;12:1286-1292 pubmed publisher..Compound 55 may represent the starting point for the development of a completely new class of therapeutics for prion diseases. ..
- Johannessen L, Sundberg T, O Connell D, Kolde R, Berstler J, Billings K, et al. Small-molecule studies identify CDK8 as a regulator of IL-10 in myeloid cells. Nat Chem Biol. 2017;13:1102-1108 pubmed publisher..These findings identify a function for CDK8 and CDK19 in regulating innate immune activation and suggest that these kinases may warrant consideration as therapeutic targets for inflammatory disorders. ..
- Drabsch Y, He S, Zhang L, Snaar Jagalska B, Ten Dijke P. Transforming growth factor-? signalling controls human breast cancer metastasis in a zebrafish xenograft model. Breast Cancer Res. 2013;15:R106 pubmed publisher..The zebrafish-embryonic breast cancer xenograft model is applicable for the mechanistic understanding, screening and development of anti-TGF-? drugs for the treatment of metastatic breast cancer in a timely and cost-effective manner. ..
- Stanford S, Bottini N. Targeting Tyrosine Phosphatases: Time to End the Stigma. Trends Pharmacol Sci. 2017;38:524-540 pubmed publisher..We describe the development of new small-molecule orthosteric, allosteric, and oligomerization-inhibiting PTP inhibitors and discuss new studies targeting the receptor PTP (RPTP) subfamily with biologics. ..
- Wenholz D, Zeng M, Ma C, Mielczarek M, Yang X, Bhadbhade M, et al. Small molecule inhibitors of bacterial transcription complex formation. Bioorg Med Chem Lett. 2017;27:4302-4308 pubmed publisher..Docking was investigated as an in silico method for the further development of the compounds. ..
- Wu F, Zhang Y, Sun B, McMahon A, Wang Y. Hedgehog Signaling: From Basic Biology to Cancer Therapy. Cell Chem Biol. 2017;24:252-280 pubmed publisher..We discuss experiences and lessons learned from the decades-long efforts toward the development of cancer therapies targeting the HH pathway. Challenges to develop next-generation cancer therapies are highlighted. ..
- Abel R, Wang L, Mobley D, Friesner R. A Critical Review of Validation, Blind Testing, and Real- World Use of Alchemical Protein-Ligand Binding Free Energy Calculations. Curr Top Med Chem. 2017;17:2577-2585 pubmed publisher..In particular, we characterized a selection bias effect which may be important in prospective free energy calculations, and introduced a strategy to improve the accuracy of the free energy predictions. ..
- Crawford T, Vartanian S, Côté A, Bellon S, Duplessis M, Flynn E, et al. Inhibition of bromodomain-containing protein 9 for the prevention of epigenetically-defined drug resistance. Bioorg Med Chem Lett. 2017;27:3534-3541 pubmed publisher..BRD9 inhibitors may therefore show utility in preventing epigenetically-defined drug resistance. ..
- Wang L, Li L, Zhou Z, Jiang Z, You Q, Xu X. Structure-based virtual screening and optimization of modulators targeting Hsp90-Cdc37 interaction. Eur J Med Chem. 2017;136:63-73 pubmed publisher..All the data suggest that compound 10 exhibits moderate inhibitory effect on Hsp90-Cdc37 and could be regard as a first evidence of a non-natural compound targeting Hsp90-Cdc37 PPI. ..
- Dey S, Anbanandam A, Mumford B, De Guzman R. Characterization of Small-Molecule Scaffolds That Bind to the Shigella Typeâ€…III Secretion System Protein IpaD. ChemMedChem. 2017;12:1534-1541 pubmed publisher..NMR mapping revealed potential hotspots in IpaD for binding small molecules. These scaffolds can be used as building blocks in developing small-molecule inhibitors of IpaD that could lead to new anti-infectives. ..
- Perez Leal O, Barrero C, Merali S. Pharmacological stimulation of nuclear factor (erythroid-derived 2)-like 2 translation activates antioxidant responses. J Biol Chem. 2017;292:14108-14121 pubmed publisher..Also, targeting this mechanism with novel compounds could provide new insights into prevention and treatment of multiple diseases in which oxidative stress plays a significant role. ..
- Kontnik R, Crawford J, Clardy J. Exploiting a global regulator for small molecule discovery in Photorhabdus luminescens. ACS Chem Biol. 2010;5:659-65 pubmed publisher..Use of this mutant expanded a family of stilbene-derived small molecules, which were known to play important roles in the symbiosis, from three members to at least nine members...
- Liao C, Hsu J, Kim Y, Hu D, Xu D, Zhang J, et al. Selective inhibition of spleen tyrosine kinase (SYK) with a novel orally bioavailable small molecule inhibitor, RO9021, impinges on various innate and adaptive immune responses: implications for SYK inhibitors in autoimmune disease therapy. Arthritis Res Ther. 2013;15:R146 pubmed publisher..RO9021 could serve as a starting point for the development of selective SYK inhibitors for the treatment of inflammation-related and autoimmune-related disorders. ..
- Makau J, Watanabe K, Ishikawa T, Mizuta S, Hamada T, Kobayashi N, et al. Identification of small molecule inhibitors for influenza a virus using in silico and in vitro approaches. PLoS ONE. 2017;12:e0173582 pubmed publisher..8-2.1 ?M. Our data demonstrate that the combined use of NUDE system followed by the cell-based assay is useful to obtain lead compounds for the development of novel anti-influenza drugs. ..
- Rohira A, Yan F, Wang L, Wang J, Zhou S, Lu A, et al. Targeting SRC Coactivators Blocks the Tumor-Initiating Capacity of Cancer Stem-like Cells. Cancer Res. 2017;77:4293-4304 pubmed publisher..i>Cancer Res; 77(16); 4293-304. ©2017 AACR. ..
- Oellers T, König D, Kostka A, Xie S, Brugger J, Ludwig A. Shape Memory Micro- and Nanowire Libraries for the High-Throughput Investigation of Scaling Effects. ACS Comb Sci. 2017;19:574-584 pubmed publisher..5 to 20 K. It is shown that a vanishing hysteresis can be achieved for special combinations of sample geometry and composition. ..
- McGovern Gooch K, Mahajani N, Garagozzo A, Schramm A, Hannah L, Sieburg M, et al. Synthetic Triterpenoid Inhibition of Human Ghrelin O-Acyltransferase: The Involvement of a Functionally Required Cysteine Provides Mechanistic Insight into Ghrelin Acylation. Biochemistry. 2017;56:919-931 pubmed publisher..This study establishes these compounds as potent small molecule inhibitors of ghrelin acylation and provides a foundation for the development of novel hGOAT inhibitors as therapeutics targeting diabetes and obesity. ..
- Chan S. MolAlign: an algorithm for aligning multiple small molecules. J Comput Aided Mol Des. 2017;31:523-546 pubmed publisher..We have compared our results with some recent publications. While an exact comparison is impossible, it is clear that our algorithm is fast and produces very competitive results. ..
- Bremer J, Skinner J, Granato M. A small molecule screen identifies in vivo modulators of peripheral nerve regeneration in zebrafish. PLoS ONE. 2017;12:e0178854 pubmed publisher..Thus, we established a technically simple assay to rapidly identify valuable entry points into pathways critical for vertebrate peripheral nerve regeneration. ..
- Monjas L, Swier L, Setyawati I, Slotboom D, Hirsch A. Dynamic Combinatorial Chemistry to Identify Binders of ThiT, an S-Component of the Energy-Coupling Factor Transporter for Thiamine. ChemMedChem. 2017;12:1693-1696 pubmed publisher..This is the first report in which DCC is used for fragment growing to an ill-defined pocket, and one of the first reports for its application with an integral membrane protein as target...
- Berndt N, Karim R, Schonbrunn E. Advances of small molecule targeting of kinases. Curr Opin Chem Biol. 2017;39:126-132 pubmed publisher..In this short review we will discuss the most recent advances, challenges, and alternatives to currently adopted strategies in this burgeoning field. ..
- Yokoyama W, Kohsaka H, Kaneko K, Walters M, Takayasu A, Fukuda S, et al. Abrogation of CC chemokine receptor 9 ameliorates collagen-induced arthritis of mice. Arthritis Res Ther. 2014;16:445 pubmed publisher..The interaction between CCL25 and CCR9 may play important roles in cell infiltration into the RA synovial tissues and inflammatory mediator production. Blocking CCL25 or CCR9 may represent a novel safe therapy for RA. ..
- Krieger V, Hamacher A, Gertzen C, Senger J, Zwinderman M, Marek M, et al. Design, Multicomponent Synthesis, and Anticancer Activity of a Focused Histone Deacetylase (HDAC) Inhibitor Library with Peptoid-Based Cap Groups. J Med Chem. 2017;60:5493-5506 pubmed publisher..Furthermore, 4j almost completely reversed the cisplatin resistance in Cal27CisR. This effect is related to a synergistic induction of apoptosis as seen in the combination of 4j with cisplatin. ..
- Scott D, Hammill J, Min J, Rhee D, Connelly M, Sviderskiy V, et al. Blocking an N-terminal acetylation-dependent protein interaction inhibits an E3 ligase. Nat Chem Biol. 2017;13:850-857 pubmed publisher..Overall, our data demonstrate that N-terminal acetyl-dependent protein interactions are druggable targets and provide insights into targeting multiprotein E2-E3 ligases...
- Sparling B, DiMauro E. Progress in the discovery of small molecule modulators of the Cys-loop superfamily receptors. Bioorg Med Chem Lett. 2017;27:3207-3218 pubmed publisher..Others offer high levels of subtype and/or inter-superfamily selectivity and have facilitated understanding of complex SAR and pharmacodynamics. ..
- Kolosenko I, Yu Y, Busker S, Dyczynski M, Liu J, Haraldsson M, et al. Identification of novel small molecules that inhibit STAT3-dependent transcription and function. PLoS ONE. 2017;12:e0178844 pubmed publisher..Taken together, using a targeted, cell-based approach, novel inhibitors of STAT-driven transcriptional activity were discovered which are interesting leads to pursue further for the development of anti-cancer therapeutic agents. ..
- Cooper J, Ou Y, McMillan E, Vaden R, Zaman A, Bodemann B, et al. TBK1 Provides Context-Selective Support of the Activated AKT/mTOR Pathway in Lung Cancer. Cancer Res. 2017;77:5077-5094 pubmed publisher..i>Cancer Res; 77(18); 5077-94. ©2017 AACR. ..
- Shah F, Stepan A, O Mahony A, Velichko S, Folias A, Houle C, et al. Mechanisms of Skin Toxicity Associated with Metabotropic Glutamate Receptor 5 Negative Allosteric Modulators. Cell Chem Biol. 2017;24:858-869.e5 pubmed publisher..The studies reported here demonstrate how phenotypic profiling of preclinical drug candidates using human primary cells can provide insights into the mechanisms of toxicity and inform early drug discovery and development campaigns. ..
- Decker P, Naujoks D, Langenkämper D, Somsen C, Ludwig A. High-Throughput Structural and Functional Characterization of the Thin Film Materials System Ni-Co-Al. ACS Comb Sci. 2017;19:618-624 pubmed publisher..All results and literature data were used to propose a ternary thin film phase diagram of the Ni-Co-Al thin film system. ..
- Chen Y, Huang J, Tang C, Chen X, Yin Z, Heng B, et al. Small molecule therapeutics for inflammation-associated chronic musculoskeletal degenerative diseases: Past, present and future. Exp Cell Res. 2017;359:1-9 pubmed publisher..In this review, we would examine and analyze recent developments in small molecule drugs for ICMDDs, suggest possible feasible improvements in treatment modalities, and discuss future research directions. ..
- Gligorich K, Vaden R, Shelton D, Wang G, Matsen C, Looper R, et al. Development of a screen to identify selective small molecules active against patient-derived metastatic and chemoresistant breast cancer cells. Breast Cancer Res. 2013;15:R58 pubmed..The low proliferation rate and chemoresistance make patient-derived cells an excellent tool in preclinical drug development. ..
- Bradley W, Arora S, Busby J, Balasubramanian S, Gehling V, Nasveschuk C, et al. EZH2 inhibitor efficacy in non-Hodgkin's lymphoma does not require suppression of H3K27 monomethylation. Chem Biol. 2014;21:1463-75 pubmed publisher..Importantly, we find that these inhibitors are broadly efficacious also in NHL models with wild-type EZH2. ..
- Narhe B, Breman A, Padwal J, Vandenput D, Scheidt J, Benningshof J, et al. Piperidine and octahydropyrano[3,4-c] pyridine scaffolds for drug-like molecular libraries of the European Lead Factory. Bioorg Med Chem. 2017;25:5160-5170 pubmed publisher..Cleavage of a terminal 1,2-diol and acid catalysed epoxide opening cyclization are the key steps involved. A number of members of a projected small-molecular library is synthesized for each scaffold. ..
- Shi B, Deng Y, Zhao P, Li X. Selecting a DNA-Encoded Chemical Library against Non-immobilized Proteins Using a "Ligate-Cross-Link-Purify" Strategy. Bioconjug Chem. 2017;28:2293-2301 pubmed publisher..In addition, this method has shown excellent capability in identifying binders with moderate and weak affinities. ..
- Admyre T, Amrot Fors L, Andersson M, Bauer M, Bjursell M, Drmota T, et al. Inhibition of AMP deaminase activity does not improve glucose control in rodent models of insulin resistance or diabetes. Chem Biol. 2014;21:1486-96 pubmed publisher..Therefore, these results do not support the development of AMPD inhibitors for the treatment of type 2 diabetes. ..
- Gadd M, Testa A, Lucas X, Chan K, Chen W, Lamont D, et al. Structural basis of PROTAC cooperative recognition for selective protein degradation. Nat Chem Biol. 2017;13:514-521 pubmed publisher..Our results elucidate how PROTAC-induced de novo contacts dictate preferential recruitment of a target protein into a stable and cooperative complex with an E3 ligase for selective degradation. ..
- Vladimer G, Snijder B, Krall N, Bigenzahn J, Huber K, Lardeau C, et al. Global survey of the immunomodulatory potential of common drugs. Nat Chem Biol. 2017;13:681-690 pubmed publisher..The approach offers an attractive platform for the personalized identification and characterization of immunomodulatory therapeutics. ..
- Brahmachari S, Paul A, Segal D, Gazit E. Inhibition of amyloid oligomerization into different supramolecular architectures by small molecules: mechanistic insights and design rules. Future Med Chem. 2017;9:797-810 pubmed publisher..The establishment of structure-function relationship for amyloid-modifying therapies by the various functional entities should serve as an important step toward the development of efficient therapeutics. ..
- Licciardello M, Ringler A, Markt P, Klepsch F, Lardeau C, Sdelci S, et al. A combinatorial screen of the CLOUD uncovers a synergy targeting the androgen receptor. Nat Chem Biol. 2017;13:771-778 pubmed publisher..Collectively, our data suggest that PPC could be repurposed to tackle resistance to antiandrogens in prostate cancer patients. ..
- Juneja M, Kobelt D, Walther W, Voss C, Smith J, Specker E, et al. Statin and rottlerin small-molecule inhibitors restrict colon cancer progression and metastasis via MACC1. PLoS Biol. 2017;15:e2000784 pubmed publisher..This is-to the best of our knowledge-the first identification of inhibitors restricting cancer progression and metastasis via the novel target MACC1. This drug repositioning might be of therapeutic value for CRC patients. ..
- Zhu J, Cuellar R, Berndt N, Lee H, Olesen S, Martin M, et al. Structural Basis of Wee Kinases Functionality and Inactivation by Diverse Small Molecule Inhibitors. J Med Chem. 2017;60:7863-7875 pubmed publisher..Combined, the data provide a comprehensive view on the catalytic and structural properties of Wee kinases and a framework for the rational design of novel inhibitors thereof. ..
- Brengel C, Thomann A, Schifrin A, Allegretta G, Kamal A, Haupenthal J, et al. Biophysical Screening of a Focused Library for the Discovery of CYP121 Inhibitors as Novel Antimycobacterials. ChemMedChem. 2017;12:1616-1626 pubmed publisher..Due to its low molecular weight, promising biological profile, and physicochemical properties, this compound is an excellent starting point for further rational optimization. ..
- Golubovskaya V, Ho B, Zheng M, Magis A, Ostrov D, Morrison C, et al. Disruption of focal adhesion kinase and p53 interaction with small molecule compound R2 reactivated p53 and blocked tumor growth. BMC Cancer. 2013;13:342 pubmed publisher..Thus, disruption of the FAK and p53 interaction with a novel small molecule reactivated p53 in cancer cells in vitro and in vivo and can be effectively used for development of FAK-p53 targeted cancer therapy approaches. ..
- Ottmann C. New Compound Classes: Protein-Protein Interactions. Handb Exp Pharmacol. 2016;232:125-38 pubmed..In this chapter examples of both inhibition as well as stabilization of PPIs are reviewed including some of the technologies which has been used for their identification." ..
- Tassini S, Sun L, Lanko K, Crespan E, Langron E, Falchi F, et al. Discovery of Multitarget Agents Active as Broad-Spectrum Antivirals and Correctors of Cystic Fibrosis Transmembrane Conductance Regulator for Associated Pulmonary Diseases. J Med Chem. 2017;60:1400-1416 pubmed publisher..We report herein the discovery of the first small molecules able to simultaneously act as correctors of the F508del-CFTR folding defect and as broad-spectrum antivirals against a panel of EVs representative of all major species. ..
- Long F, Nicholls R, Emsley P, Graǽulis S, Merkys A, Vaitkus A, et al. AceDRG: a stereochemical description generator for ligands. Acta Crystallogr D Struct Biol. 2017;73:112-122 pubmed publisher..AceDRG employs RDKit for chemistry perception and for initial conformation generation, as well as for the interpretation of SMILES strings, SDF MOL and SYBYL MOL2 files. ..
- Zhang L, Dewan V, Yin H. Discovery of Small Molecules as Multi-Toll-like Receptor Agonists with Proinflammatory and Anticancer Activities. J Med Chem. 2017;60:5029-5044 pubmed publisher..These results showcase potential therapeutic applications of 17e in both vaccine adjuvants and anticancer therapies based on multi-TLR activation. ..