Spliceostatin A interaction with SF3B limits U1 snRNP availability and causes premature cleavage and polyadenylation [0.03%]
.spliceostatin A与SF3B的结合限制了U1 snRNP的可用性并导致提前转录终止及多腺苷酸化
Rei Yoshimoto,Jagat K Chhipi-Shrestha,Tilman Schneider-Poetsch et al.
Rei Yoshimoto et al.
RNA splicing, a highly conserved process in eukaryotic gene expression, is seen as a promising target for anticancer agents. Splicing is associated with other RNA processing steps, such as transcription and nuclear export; however, our unde...
Molecular basis of C-S bond cleavage in the glycyl radical enzyme isethionate sulfite-lyase [0.03%]
甘氨酰自由基酶异硫酸酯类硫酸盐裂解酶切断C-S键的分子机理研究
Christopher D Dawson,Stephania M Irwin,Lindsey R F Backman et al.
Christopher D Dawson et al.
Desulfonation of isethionate by the bacterial glycyl radical enzyme (GRE) isethionate sulfite-lyase (IslA) generates sulfite, a substrate for respiration that in turn produces the disease-associated metabolite hydrogen sulfide. Here, we pre...
Degradation from the outside in: Targeting extracellular and membrane proteins for degradation through the endolysosomal pathway [0.03%]
由外而内的降解：通过内吞溶酶体途径对外部和膜蛋白进行靶向降解
Green Ahn,Steven M Banik,Carolyn R Bertozzi
Green Ahn
Targeted protein degradation (TPD) is a promising strategy to remove deleterious proteins for therapeutic benefit and to probe biological pathways. The past two decades have witnessed a surge in the development of technologies that rely on ...
Resistance of Mycobacterium tuberculosis to indole 4-carboxamides occurs through alterations in drug metabolism and tryptophan biosynthesis [0.03%]
结核分枝杆菌通过改变药物代谢和色氨酸生物合成对吲哚-4-羧酰胺耐药
M Daben J Libardo,Caroline J Duncombe,Simon R Green et al.
M Daben J Libardo et al.
Tryptophan biosynthesis represents an important potential drug target for new anti-TB drugs. We identified a series of indole-4-carboxamides with potent antitubercular activity. In vitro, Mycobacterium tuberculosis (Mtb) acquired resistance...
Bioreporters for direct mode of action-informed screening of antibiotic producer strains [0.03%]
用于抗生素产生菌株直接作用机制筛选的生物报告基因体系
Katharina W Wex,Julian S Saur,Franziska Handel et al.
Katharina W Wex et al.
A big challenge in natural product research of today is rapid dereplication of already known substances, to free capacities for the exploration of new agents. Prompt information on bioactivities and mode of action (MOA) speeds up the lead d...
Repurposing of glycine transport inhibitors for the treatment of erythropoietic protoporphyria [0.03%]
再利用甘氨酸运输抑制剂治疗原发性溶血性卟啉病
François Halloy,Pavithra S Iyer,Alice Ghidini et al.
François Halloy et al.
Erythropoietic protoporphyria (EPP) is a rare disease in which patients experience severe light sensitivity. It is caused by a deficiency of ferrochelatase (FECH), the last enzyme in heme biosynthesis (HBS). The lack of FECH causes accumula...
High-content phenotypic and pathway profiling to advance drug discovery in diseases of unmet need [0.03%]
高内涵表型和途径谱分析促进未满足临床需求疾病的药物研发
Rebecca E Hughes,Richard J R Elliott,John C Dawson et al.
Rebecca E Hughes et al.
Conventional thinking in modern drug discovery postulates that the design of highly selective molecules which act on a single disease-associated target will yield safer and more effective drugs. However, high clinical attrition rates and th...
Slava Ziegler,Sonja Sievers,Herbert Waldmann
Slava Ziegler
Profiling approaches such as gene expression or proteome profiling generate small-molecule bioactivity profiles that describe a perturbed cellular state in a rather unbiased manner and have become indispensable tools in the evaluation of bi...
Phenotypic screening with target identification and validation in the discovery and development of E3 ligase modulators [0.03%]
表型筛选结合靶点鉴定与验证在E3连接酶调节剂研发中的应用
Nil Ege,Habib Bouguenina,Marianthi Tatari et al.
Nil Ege et al.
The use of phenotypic screening was central to the discovery and development of novel thalidomide analogs, the IMiDs (immunomodulatory drugs) agents. With the discovery that these agents bind the E3 ligase, CRL4CRBN, and alter its substrate...
Anna P Hnatiuk,Francesca Briganti,David W Staudt et al.
Anna P Hnatiuk et al.
Human induced pluripotent stem cells (hiPSCs) have emerged as a promising platform for pharmacogenomics and drug development. In cardiology, they make it possible to produce unlimited numbers of patient-specific human cells that reproduce h...