Abstract:
:In this issue of Cell Chemical Biology, Harvey et al. (2020) identify 4E14, a sulfhydryl-containing N-acetyltryptophan analog that selectively disrupts binding to the previously undruggable anti-apoptotic BCL2 paralog BFL1, and elucidate a BFL1 conformational change that facilitates 4E14 interaction. These results provide insight that will accelerate development of BFL1 inhibitors.
journal_name
Cell Chem Bioljournal_title
Cell chemical biologyauthors
Dai H,Meng XW,Kaufmann SHdoi
10.1016/j.chembiol.2020.05.014subject
Has Abstractpub_date
2020-06-18 00:00:00pages
639-642issue
6eissn
2451-9456issn
2451-9448pii
S2451-9456(20)30191-4journal_volume
27pub_type
杂志文章abstract::Phenotypic drug discovery offers some advantages over target-based methods, mainly because it allows drug leads to be tested in systems that more closely model distinct disease states. However, a potential disadvantage is the difficulty of linking the observed phenotype to a specific cellular target. To address this p...
journal_title:Cell chemical biology
pub_type: 杂志文章
doi:10.1016/j.chembiol.2016.08.011
更新日期:2016-10-20 00:00:00
abstract::In this issue of Cell Chemical Biology, Diaz et al. (2017) report a strategy to achieve temporal, spatial, and stoichiometric control over the protein kinase cAbl in living cells. They achieve this by splitting cAbl into two inactive fragments that form an active kinase upon small molecule addition, potentially provid...
journal_title:Cell chemical biology
pub_type: 杂志文章
doi:10.1016/j.chembiol.2017.10.004
更新日期:2017-10-19 00:00:00
abstract::Depalmitoylases play a crucial role in regulating dynamic protein palmitoylation. In this issue of Cell Chemical Biology, Amara et al. (2019) present fluorogenic peptide probes to analyze the activity and substrate specificity of depalmitoylases and uncover that the amino acid residues distal to the palmitoylation sit...
journal_title:Cell chemical biology
pub_type: 评论,杂志文章
doi:10.1016/j.chembiol.2018.12.008
更新日期:2019-01-17 00:00:00
abstract::Cryptochrome 1 (CRY1) and CRY2 are core regulators of the circadian clock, and the development of isoform-selective modulators is important for the elucidation of their redundant and distinct functions. Here, we report the identification and functional characterization of a small-molecule modulator of the mammalian ci...
journal_title:Cell chemical biology
pub_type: 杂志文章
doi:10.1016/j.chembiol.2020.05.008
更新日期:2020-09-17 00:00:00
abstract::The translation of functionally active natural products into fully synthetic small-molecule mimetics has remained an important process in medicinal chemistry. We recently discovered that the terpene natural product nimbolide can be utilized as a covalent recruiter of the E3 ubiquitin ligase RNF114 for use in targeted ...
journal_title:Cell chemical biology
pub_type: 杂志文章
doi:10.1016/j.chembiol.2021.01.005
更新日期:2021-01-22 00:00:00
abstract::USP7 is a deubiquitinating enzyme that plays a pivotal role in multiple oncogenic pathways and therefore is a desirable target for new anti-cancer therapies. However, the lack of structural information about the USP7-inhibitor interactions has been a critical gap in the development of potent inhibitors. USP7 is unique...
journal_title:Cell chemical biology
pub_type: 杂志文章
doi:10.1016/j.chembiol.2017.09.004
更新日期:2017-12-21 00:00:00
abstract::In this study we developed an efficient method to prepare glycoengineered β-N-acetylhexosaminidase containing multiple mannose-6-phosphates (M6Ps) by combining genetic code expansion with bioorthogonal ligation techniques. We found that multiple M6P-conjugated enzymes were produced with a high efficiency by using comb...
journal_title:Cell chemical biology
pub_type: 杂志文章
doi:10.1016/j.chembiol.2018.07.011
更新日期:2018-10-18 00:00:00
abstract::Because small-molecule activators of adenylyl cyclases (AC) affect ACs cell-wide, it is challenging to explore the signaling consequences of AC activity emanating from specific intracellular compartments. We explored this issue using a series of engineered, optogenetic, spatially restricted, photoactivable adenylyl cy...
journal_title:Cell chemical biology
pub_type: 杂志文章
doi:10.1016/j.chembiol.2019.07.004
更新日期:2019-10-17 00:00:00
abstract::Optically controlled chemical reagents, termed "photopharmaceuticals," are powerful tools for precise spatiotemporal control of proteins particularly when genetic methods, such as knockouts or optogenetics are not viable options. However, current photopharmaceutical scaffolds, such as azobenzenes are intolerant of GFP...
journal_title:Cell chemical biology
pub_type: 杂志文章
doi:10.1016/j.chembiol.2020.11.007
更新日期:2020-11-27 00:00:00
abstract::In this issue of Cell Chemical Biology, Shah et al. (2019) report an in vitro, high-throughput assay that predicts the ability of compounds to suppress peroxidation of phospholipids. This approach provides a way to design and optimize targeted antioxidants that suppress specific oxidative event in cells, potentially o...
journal_title:Cell chemical biology
pub_type: 评论,杂志文章
doi:10.1016/j.chembiol.2019.11.003
更新日期:2019-11-21 00:00:00
abstract::Anti-apoptotic BCL-2 family proteins block cell death by trapping the critical α-helical BH3 domains of pro-apoptotic members in a surface groove. Cancer cells hijack this survival mechanism by overexpressing a spectrum of anti-apoptotic members, mounting formidable apoptotic blockades that resist chemotherapeutic tre...
journal_title:Cell chemical biology
pub_type: 杂志文章
doi:10.1016/j.chembiol.2016.07.022
更新日期:2016-09-22 00:00:00
abstract::Despite widespread interest for understanding how modified bases have evolved their contemporary functions, limited experimental evidence exists for measuring how close an organism is to accidentally creating a new, modified base within the framework of its existing genome. Here, we describe the biochemical and struct...
journal_title:Cell chemical biology
pub_type: 杂志文章
doi:10.1016/j.chembiol.2020.09.006
更新日期:2021-01-21 00:00:00
abstract::Rhomboid-family intramembrane proteases regulate important biological processes and have been associated with malaria, cancer, and Parkinson's disease. However, due to the lack of potent, selective, and pharmacologically compliant inhibitors, the wide therapeutic potential of rhomboids is currently untapped. Here, we ...
journal_title:Cell chemical biology
pub_type: 杂志文章
doi:10.1016/j.chembiol.2017.09.007
更新日期:2017-12-21 00:00:00
abstract::Genetically encoded biosensors are useful tools for detecting the presence and levels of diverse biomolecules in living cells. However, low-abundance targets are difficult to detect because they are often unable to bind and activate enough biosensors to detect using standard microscopic imaging approaches. Here we des...
journal_title:Cell chemical biology
pub_type: 杂志文章
doi:10.1016/j.chembiol.2019.01.005
更新日期:2019-04-18 00:00:00
abstract::Janus kinases (JAKs) are a family of cytoplasmatic tyrosine kinases that are attractive targets for the development of anti-inflammatory drugs given their roles in cytokine signaling. One question regarding JAKs and their inhibitors that remains under intensive debate is whether JAK inhibitors should be isoform select...
journal_title:Cell chemical biology
pub_type: 杂志文章
doi:10.1016/j.chembiol.2016.10.008
更新日期:2016-11-17 00:00:00
abstract::G-quadruplexes are specialized secondary structures in nucleic acids that possess significant conformational polymorphisms. The precise G-quadruplex conformations in vivo and their relevance to biological functions remain controversial and unclear, especially for telomeric G-quadruplexes. Here, we report a novel singl...
journal_title:Cell chemical biology
pub_type: 杂志文章
doi:10.1016/j.chembiol.2016.08.013
更新日期:2016-10-20 00:00:00
abstract::Disease sites in atherosclerosis and cancer feature cell masses (e.g., plaques/tumors), a low pH extracellular microenvironment, and various pro-inflammatory cytokines such as tumor necrosis factor α (TNFα). The ability to engineer a cell to seek TNFα sources allows for targeted therapeutic delivery. To accomplish thi...
journal_title:Cell chemical biology
pub_type: 杂志文章
doi:10.1016/j.chembiol.2017.05.008
更新日期:2017-06-22 00:00:00
abstract::The discovery of novel small molecules that induce stem cell reprogramming and give efficient access to pluripotent stem cells is of major importance for potential therapeutic applications and may reveal novel insights into the factors controlling pluripotency. Chemical reprogramming of mouse epiblast stem cells (EpiS...
journal_title:Cell chemical biology
pub_type: 杂志文章
doi:10.1016/j.chembiol.2016.02.015
更新日期:2016-04-21 00:00:00
abstract::Contrary to the classic model of protein kinase A (PKA) residing outside of the nucleus, we identify a nuclear signaling complex that consists of AKAP95, PKA, and PDE4D5 and show that it forms a functional cyclic AMP (cAMP) signaling microdomain. Locally generated cAMP can accumulate within the vicinity of this comple...
journal_title:Cell chemical biology
pub_type: 杂志文章
doi:10.1016/j.chembiol.2019.03.003
更新日期:2019-06-20 00:00:00
abstract::In this issue of Cell Chemical Biology, Ortega et al. (2016) determine the structure of another lantibiotic dehydratase with a tRNA(Glu)-dependent mechanism of modification. Moreover, they identify a common recognition motif involved in leader peptide binding in a number of different peptide-modification enzymes. Thes...
journal_title:Cell chemical biology
pub_type: 评论,杂志文章
doi:10.1016/j.chembiol.2016.03.001
更新日期:2016-03-17 00:00:00
abstract::Acyl-coenzyme A (CoA)/protein interactions are essential for life. Despite this importance, their global scope and selectivity remains undefined. Here, we describe CATNIP (CoA/AcetylTraNsferase Interaction Profiling), a chemoproteomic platform for the high-throughput analysis of acyl-CoA/protein interactions in endoge...
journal_title:Cell chemical biology
pub_type: 杂志文章
doi:10.1016/j.chembiol.2019.11.011
更新日期:2020-03-19 00:00:00
abstract::In this issue of Cell Chemical Biology, Olson et al. (2019) develop the first selective CDK7 irreversible inhibitor. Elegant cell-based studies using a CDK7 mutant that is not covalently engaged by the probe helped decipher the effects of inhibiting the kinase on the cell cycle and gene transcription. ...
journal_title:Cell chemical biology
pub_type: 评论,杂志文章
doi:10.1016/j.chembiol.2019.05.012
更新日期:2019-06-20 00:00:00
abstract::Rifamycin monooxygenases (Rox) are present in a variety of environmental bacteria and are associated with decomposition of the clinically utilized antibiotic rifampin. Here we report the structure and function of a drug-inducible rox gene from Streptomyces venezuelae, which encodes a class A flavoprotein monooxygenase...
journal_title:Cell chemical biology
pub_type: 杂志文章
doi:10.1016/j.chembiol.2018.01.009
更新日期:2018-04-19 00:00:00
abstract::Poly(ADP-ribose) polymerase (PARP) inhibitors (PARPi) are a promising class of targeted cancer drugs, but their individual target profiles beyond the PARP family, which could result in differential clinical use or toxicity, are unknown. Using an unbiased, mass spectrometry-based chemical proteomics approach, we genera...
journal_title:Cell chemical biology
pub_type: 杂志文章
doi:10.1016/j.chembiol.2016.10.011
更新日期:2016-12-22 00:00:00
abstract::Recent advances in induced pluripotent stem cell technologies and phenotypic screening shape the future of bioactive small-molecule discovery. In this review we analyze the impact of small-molecule phenotypic screens on drug discovery as well as on the investigation of human development and disease biology. We further...
journal_title:Cell chemical biology
pub_type: 杂志文章,评审
doi:10.1016/j.chembiol.2019.05.007
更新日期:2019-08-15 00:00:00
abstract::The unique photophysical properties of lanthanides, such as europium, terbium, and ytterbium, make them versatile molecular probes of biological systems. In particular, their long-lived photoluminescence, narrow bandwidth emissions, and large Stokes shifts enable experiments that are infeasible with organic fluorophor...
journal_title:Cell chemical biology
pub_type: 杂志文章,评审
doi:10.1016/j.chembiol.2020.07.009
更新日期:2020-08-20 00:00:00
abstract::Kinase inhibitors are effective cancer therapies. Unfortunately, drug resistance emerges in response to kinase inhibition leading to loss of drug efficacy. In this issue of Cell Chemical Biology, Peh et al. (2018) demonstrate that caspase activators effectively delay onset of resistance to kinase inhibitors and are ex...
journal_title:Cell chemical biology
pub_type: 评论,杂志文章
doi:10.1016/j.chembiol.2018.08.001
更新日期:2018-08-16 00:00:00
abstract::Epidermal growth factor receptor (EGFR) is a target of signal-derived H2O2, and oxidation of active-site cysteine 797 to sulfenic acid enhances kinase activity. Although a major class of covalent drugs targets C797, nothing is known about its catalytic importance or how S-sulfenylation leads to activation. Here, we re...
journal_title:Cell chemical biology
pub_type: 杂志文章
doi:10.1016/j.chembiol.2016.05.017
更新日期:2016-07-21 00:00:00
abstract::4'-Ethynyl-2-fluoro-2'-deoxyadenosine (EFdA/MK-8591), a nucleoside reverse transcriptase inhibitor (NRTI) under clinical trials, is a potent and promising long-acting anti-HIV type 1 (HIV-1) agent. EFdA and its derivatives possess a modified 4'-moiety and potently inhibit the replication of a wide spectrum of HIV-1 st...
journal_title:Cell chemical biology
pub_type: 杂志文章
doi:10.1016/j.chembiol.2018.07.014
更新日期:2018-10-18 00:00:00
abstract::ATP is an important energy metabolite and allosteric signal in health and disease. ATP-interacting proteins, such as P2 receptors, control inflammation, cell death, migration, and wound healing. However, identification of allosteric ATP sites remains challenging, and our current inventory of ATP-controlled pathways is...
journal_title:Cell chemical biology
pub_type: 杂志文章
doi:10.1016/j.chembiol.2020.05.010
更新日期:2020-08-20 00:00:00