Transport specificity of FpvA and FpvB for pyoverdine-antibiotic conjugates in Pseudomonas aeruginosa [0.03%]
铜绿假单胞菌中FpvA和FpvB对吡咯渡铁素-抗生素缀合物的转运特异性
Johan Revol-Tissot,Christine Cézard,Anne Forster et al.
Johan Revol-Tissot et al.
Pyoverdines (PVDs) are fluorescent siderophores produced by many Pseudomonas species. In P. aeruginosa, the TonB-dependent transporters (TBDT) FpvA and FpvB mediate PVD-dependent iron acquisition. PVDs have emerged as promising vectors for ...
Design and engineering of μO-conotoxin MfVIA mutants to enhance NaV1.8 inhibition and analgesic efficacy in inflammatory pain [0.03%]
设计和工程改造μO-康托克斯肽MfVIA突变体以增强对NaV1.8的抑制作用及在炎症痛中的镇痛功效
Xinyu Gao,Nan Wang,Leqing Zhan et al.
Xinyu Gao et al.
Voltage-gated sodium (NaV) channels are essential for action potential initiation and propagation and play key roles in pain signaling. NaV1.8 is predominantly expressed in nociceptors and drives persistent sodium currents that support repe...
Xianqiang Yu,Dingyan Yu,Ye Wang et al.
Xianqiang Yu et al.
Antibody-drug conjugates (ADCs) represent a major advance in precision cancer therapy by combining the high target specificity of monoclonal antibodies with the potent cytotoxicity of small-molecule payloads through chemical linkers. Among ...
CDK4/6-targeted therapy: From clinical inhibitors to emerging strategies to overcome resistance [0.03%]
CDK4/6靶向治疗：从临床抑制剂到克服耐药性的新兴策略
Wenjie Sha,Dijing Feng,Zitong Yan et al.
Wenjie Sha et al.
The Cyclin-dependent kinase 4/6 (CDK4/6) complex orchestrates the critical G1-to-S phase transition by phosphorylating the Retinoblastoma protein (Rb), establishing it as a validated therapeutic target in oncology. The clinical deployment o...
Coumarin-sulfonamide hybrids as PKM2 activators induce metabolic reprogramming and suppress ovarian cancer cell growth [0.03%]
香豆素磺胺类PKM2激活剂通过诱导代谢重编程抑制卵巢癌细胞生长
Deep Rohan Chatterjee,Gourav Choudhary,Shailendra Sharma et al.
Deep Rohan Chatterjee et al.
Coumarin-piperazine sulfonamides (CPS series) were rationally designed as hybrid modulators of pyruvate kinase M2 (PKM2) to exploit metabolic vulnerabilities in ovarian cancer. Phenotypic screening across cancer cell lines guided hit identi...
Recent advances in the development of small-molecule drugs based on covalent reversible inhibitors [0.03%]
基于可逆共价抑制剂的小分子药物开发进展
Zi Ye,Jiubo Sun,Chong-Jing Zhang
Zi Ye
Reversible covalent inhibitors (RCIs) are a class of small-molecule drugs that engage target proteins through covalent bonds. Unlike irreversible covalent inhibitors, RCIs can dissociate from their target. This reversibility, combined with ...
Computational hybrid approach of PBPK simulation and CGCNN models for human intravenous pharmacokinetics [0.03%]
基于PBPK模拟和CGCNN模型的计算杂化方法在人类静脉药代动力学中的应用
Kiyoshi Hasegawa,Yuya Seki
Kiyoshi Hasegawa
In drug discovery, it is not sufficient for a lead compound to exhibit high binding affinity for the target protein alone. It is equally important to predict an optimal pharmacokinetic (PK) profile that reflects the physicochemical properti...
Assessing the use of foundation model embeddings to improve drug response predictions using scRNA-Seq expression data [0.03%]
利用基础模型嵌入改进使用单细胞基因表达数据的药物反应预测
William Davey,Yu Liu,Kiyoshi Hasegawa
William Davey
Cancer drug response (CDR) prediction is challenging due to tumor heterogeneity and limited amount of high-quality response data. Large foundation models trained on single-cell RNA-Seq data have been reported to improve the performance of a...
Sequence specificity of peptide nucleic acids containing terminal cationic amino acids [0.03%]
含末端阳离子氨基酸的肽核酸的序列特异性
Simeon O Kwange,Rambabu Dakarapu,Sarah L Wicks et al.
Simeon O Kwange et al.
Molecular recognition of DNA/RNA by peptide nucleic acids (PNAs) has proven to be a successful strategy to create research and diagnostic tools. An ongoing challenge in the development of useful PNAs has been optimizing sequence specificity...
Functionalization of cyclotriveratrilene with tetrazole and phenothiazine for doxorubicin coordination and delivery [0.03%]
用于阿霉素配位和递送的四氮唑和吩噻嗪修饰的cyclotriveratrilene功能化
Nallagari Bharath Sagar Reddy,Haritha Rengamanar,Shabir Hyder Wani et al.
Nallagari Bharath Sagar Reddy et al.
We successfully synthesized cyclotriveratrilene functionalized with the hydrophilic heterocycles tetrazole and phenothiazine, which are commonly used to modify drug molecules. We examined their ability to coordinate doxorubicin in a dimethy...