Rational Redesign of an α-Helical Marine Toxin Scaffold Enables a Safe and Broad-Spectrum Anti-ESKAPE Lipopeptide [0.03%]
合理设计α-螺旋海洋毒素支架以获得安全有效的广谱抗ESKAPE肽类抗生素
Junjie Zhang,Fawei He,Yurui Wang et al.
Junjie Zhang et al.
The surge in multidrug-resistant (MDR) pathogens necessitates novel therapeutic strategies. Here, we report the rational design of C4-VG7, an N-terminal butyrylated lipopeptide engineered from a compact, cationic, helix-compatible segment o...
Design, Synthesis, and Antitumor Evaluation of Novel Shikonin Derivatives: Discovery of 3k as a Dual Activator of the Integrated Stress Response and ROS in Gastric Cancer [0.03%]
新型紫草素衍生物的设计、合成及抗肿瘤评价：3k通过激活胃癌细胞内整合应激反应和ROS的新机制
Bei Zhang,Zhipeng Xu,Danmei Tian et al.
Bei Zhang et al.
Shikonin is a natural naphthoquinone with anticancer activity; however, its therapeutic potential is limited by modest potency and suboptimal drug-like properties. To address these limitations, we designed and synthesized 31 shikonin deriva...
Mariateresa Giustiniano,Daniele Castagnolo,Antimo Gioiello et al.
Mariateresa Giustiniano et al.
Medicinal Chemistry Innovation in Australia and New Zealand (2021-2025) [0.03%]
澳大利亚和新西兰的药物化学创新（2021-2025）
Nitin A Patil,Varsha J Thombare
Nitin A Patil
Discovery of a Highly Potent and Efficient BRD9 Degrader with Strong In Vivo Antitumor Activity [0.03%]
一种高效强力BRD9降解剂及其体内抗肿瘤活性研究
Xin Tang,Yumin Huang,Cheng Zhang et al.
Xin Tang et al.
BRD9, a distinctive subunit of the ncBAF complex, is a critical regulator of acute myeloid leukemia (AML). Here, we designed, synthesized, and evaluated a series of BRD9 PROTACs. Among them, compound 27 (XYD224) was identified as a highly p...
Double-Stapled Peptide Scan Yields Potent Fusion Inhibitors of Respiratory Syncytial Virus [0.03%]
双 staple 肽扫描产生强效的呼吸道合胞病毒融合抑制剂
Nadège Pidoux,Logan Roh,Nancy Nicolet et al.
Nadège Pidoux et al.
Respiratory syncytial virus infection (RSV) is a major global health concern, particularly in infants and elderly populations. In this work, we have screened and identified 3 double-stapled peptides derived from a minimal domain of the RSV ...
Discovery of the Orally Bioavailable Isoform Selective Janus Kinase 1 (JAK1) Compound Povorcitinib (INCB054707) for the Treatment of Inflammatory and Autoimmune Diseases [0.03%]
一种口服生物可利用的Janus激酶1（JAK1）同种型选择性抑制剂Povorcitinib（INCB054707）的新药发现用于治疗炎症和自身免疫性疾病
Jincong Zhuo,Yun-Long Li,Ding-Quan Qian et al.
Jincong Zhuo et al.
Aberrant JAK2 signaling is a key driver in cancers such as myeloproliferative neoplasms (MPNs), whereas JAK1 acts as a central mediator of autoimmune and inflammatory diseases. Since JAK2 supports blood cell production, its inhibition can l...
Lysine-Targeted Covalent Inhibitors: Emerging Warheads and Expanding Applications in Medicinal Chemistry [0.03%]
靶向赖氨酸的共价抑制剂：药物化学中新先导和新应用
Yue Wu,Yafen Chen,Ruiheng Cao et al.
Yue Wu et al.
Covalent inhibition has re-emerged as a central strategy in drug discovery, yet most successes have focused on cysteine residues. Expanding covalent design to other nucleophilic amino acids offers new opportunities to overcome resistance, b...
Discovery of Dual A2A/A2B Adenosine Receptor Antagonist and Clinical Candidate INCB106385 [0.03%]
新型双A2A/A2B腺苷受体拮抗剂临床候选药物INCB106385的发现
Chao Qi,Matthew S McCammant,Yong Li et al.
Chao Qi et al.
Suppression of immune checkpoint pathways enables tumor cells to take over immunoregulatory functions, promoting cell growth and proliferation. Elevated adenosine production in the tumor microenvironment suppresses immune checkpoint control...
Discovery Process of Enlicitide, a Highly Engineered Macrocyclic Peptide Therapeutic, through Issue-Driven Fragment-Based Synthetic Assembly and SAR [0.03%]
通过以问题为导向的片段基于合成组装和构效关系研究而发现Enlicitide（一种高度工程化的环肽药物）的过程研究
Hubert Josien,Anilkumar G Nair,Fa-Xiang Ding et al.
Hubert Josien et al.
Herein, we report the discovery process of enlicitide (MK-0616, compound 18), an orally active macrocyclic peptide therapeutic against PCSK9 for LDL-C reduction. To overcome development bottlenecks in a prior lead (compound 1a) in a timely ...