Identification of TYK2 activators. Part 2: Optimization of terminal alkyne substituents to enhance activation potency [0.03%]
TYK2活化剂的鉴定. 第2部分：优化末端炔烃取代基以增强激活效力
Hirokazu Matsumoto,Tien-Cheng Wang,Fumio Nakajima et al.
Hirokazu Matsumoto et al.
Tyrosine kinase 2 (TYK2) plays a key role in immune signaling, and its inhibition has been clinically validated for autoimmune diseases. Conversely, activation of TYK2 is expected to enhance antitumor immunity, representing a novel therapeu...
Synthesis and biological investigation of phenothiazine-based derivatives as potential HDAC6 inhibitors for treatment of glioblastoma multiforme [0.03%]
茋类衍生物作为组蛋白去乙酰化酶6抑制剂的研究及其对多形性胶质母细胞瘤的治疗潜力评估
Ying Xu,Yanli Zhao,Kehui Chen et al.
Ying Xu et al.
Glioblastoma multiforme (GBM) remains a challenging brain tumor, necessitating innovative therapeutic approaches. Targeting histone deacetylase 6 (HDAC6), a cytosolic isoform implicated in oncogenic pathways, represents a promising strategy...
Solid-phase synthesis and antimicrobial activities of lipid-neomycin conjugates [0.03%]
脂质-新霉素缀合物的固相合成及其抗菌活性
Sandra Story,Sayantan Bhaduri,Dev P Arya
Sandra Story
Lipid linked aminosugars have been shown to have significant antimicrobial properties. We report here a solid phase strategy for the rapid synthesis of lipid-aminoglycoside compounds, linked with amino acids. Subsequent screening of the com...
Discovery of a potent sGC stimulator with once-daily dosing potential for the treatment of hypertension [0.03%]
用于治疗高血压的每日一次给药的可能性强大的sGC刺激剂的发现
Subharekha Raghavan,Linda Brockunier,Jian Guo et al.
Subharekha Raghavan et al.
Endothelial dysfunction and impaired NO-sGC - cGMP signaling in hypertension drive the need for next-generation soluble guanylate cyclase (sGC) stimulators with improved pharmacokinetics and once-daily dosing potential. Metabolism-guided op...
OracleScreen-LILRB4 (HTS-Oracle v3): machine learning-guided discovery of myeloid immune checkpoint binders validated in patient-derived cells [0.03%]
基于机器学习的髓系免疫检查点抑制剂筛选及其在患者来源细胞中的验证(HTS-Oracle v3：LILRB4方向)
Somaya A Abdel-Rahman,Moustafa T Gabr
Somaya A Abdel-Rahman
The identification of small molecule modulators of immune checkpoint proteins remains a significant challenge in drug discovery due to the flat, featureless nature of protein-protein interaction interfaces and the characteristically low hit...
Rational design and N-terminal acylation of a lactam-cyclized 11-residue antimicrobial peptide for improved antibacterial potency [0.03%]
具有改善抗菌活性的乳酰胺环化十一肽的设计与N-末端乙酰化
Jinhua Zhang,Guancheng Liu,Zhiyi Jiang et al.
Jinhua Zhang et al.
Linear antimicrobial peptides frequently suffer from low potency and narrow spectrum, restricting their clinical utility. Starting from the natural amphipathic α-helical peptide FAKWAFKWLKK-NH2, we rationally introduced an i, i + 7 side-ch...
Rational design, synthesis, and biological evaluation of chalcone hybrids including benzoylpiperazin (phenylacetylpiperazin)-thiophene as anti- Alzheimer's agents [0.03%]
合理设计、合成及生物评价新型查尔康素杂化化合物（包括苯甲酰哌嗪（苯乙酰哌嗪）-噻吩类）作为抗阿尔茨海默病药物的研究与发展
Zhiqi Lin,Liwei Hu,Yuanxiu Liu et al.
Zhiqi Lin et al.
A series of chalcone hybrids including benzoylpiperazin (phenylacetylpiperazin)-thiophene were designed, synthesized and evaluated their inhibitory activities against cholinesterase (ChE). All compounds displayed good inhibitory activities ...
New aminopiperidine-azoles as antifungal agents against Candida albicans with mechanistic insights into the cAMP-PKA pathway [0.03%]
具有作用于卡帕莫氏属白色铸丰球拟酵母机制的新氨杂环哌啶类抗真菌剂
Rui Guo,Yingliang Wei,Ting Yao et al.
Rui Guo et al.
Candida albicans infections are becoming increasingly prevalent, making the development of new drugs an urgent priority. In this study, a series of new aminopiperidine-azole derivatives were designed, synthesized, and evaluated for their in...
Novel 1H-pyrrole-2,5-dione derivatives as potential anti-diabetic agents: design, synthesis, in vitro, in ovo, and molecular docking studies [0.03%]
新型1h-吡咯并[2,3-c]吡唑-2,5-二酮衍生物作为抗糖尿病药物：设计、合成及体内外活性和分子对接研究
Dilan Gezer,Zeynep Ozyıldız,Zeliha Gokmen et al.
Dilan Gezer et al.
Diabetes mellitus (DM) is the most common metabolism-related health problem across the world and new therapeutics are still emerging into the market. One of the treatments is the inhibition of α-glucosidase, which is a validated therapeuti...
Design, synthesis and biological evaluation of novel CDK8/BRD4 dual inhibitors [0.03%]
新型CDK8/BRD4双靶点抑制剂的设计、合成及生物活性评价
Guoao Liang,Xiaochu Zhang,Jiayi Zhu et al.
Guoao Liang et al.
CDK8 is recognized as an important therapeutic target in colorectal cancer. Recently, a study has demonstrated that inhibition of CDK8 alone can activate a compensatory BRD4 signaling pathway, which may account for the modest in vivo effica...