Discovery of Casdatifan, Part II: A Potent and Orally Bioavailable Inhibitor of Hypoxia Inducible Factor-2α [0.03%]
Casdatifan的发现（第二部分）：一种强有力的缺氧诱导因子-2α口服抑制剂
Artur K Mailyan,Guillaume Mata,Joel W Beatty et al.
Artur K Mailyan et al.
Hypoxia-inducible factor 2α (HIF-2α) is recognized as a key oncogenic driver in clear cell renal cell carcinoma (ccRCC), the most prevalent type of kidney cancer. Here, we describe the discovery of a highly potent and selective tetralin-b...
Thiazole-Linked N-Hydroxypropanamide Derivatives: Selective HDAC6 Inhibitors with Therapeutic Potential for Neurodegenerative Diseases [0.03%]
噻唑连接的N-羟基丙酰胺衍生物：一类具有治疗神经退行性疾病潜力的选择性HDAC6抑制剂
Gibeom Nam,Jun Min Jung,Seyun Yang et al.
Gibeom Nam et al.
HDAC6 is a promising therapeutic target for the treatment of cancer and neurodegenerative and inflammatory diseases. We have developed a thiazolyl alkyl hydroxamate scaffold as an HDAC6-selective inhibitor. Herein, we synthesized new thiazo...
Identification of a Potent and Selective Small-Molecule Inhibitor Targeting the nNOS-PDZ Domain that Exhibits Rapid In Vivo Antidepressant Efficacy [0.03%]
一种有效且具有高度选择性的针对nNOS-PDZ结构域的小分子抑制剂：可快速产生体内抗抑郁功效
Liting Zhang,Zijie Xiong,Shasha Chen et al.
Liting Zhang et al.
The PDZ domain of neuronal nitric oxide synthase (nNOS-PDZ) plays a crucial role in regulating serotonin signaling in the forebrain and has emerged as a promising target for developing rapid-acting antidepressants. Here, we report the ident...
Structure-Guided Discovery of Potent, Selective, and Orally Bioavailable Werner Syndrome RecQ Helicase Inhibitors for the Treatment of Microsatellite Instability-High Tumors [0.03%]
基于结构的威斯纳氏症RecQ解旋酶抑制剂的设计：用于微卫星不稳定性高肿瘤治疗的高效、选择性和口服生物利用度化合物的研究
Qibang Sui,Dan Wang,Hui Hou et al.
Qibang Sui et al.
Despite recent advances in immunotherapy for microsatellite instability-high (MSI-H) tumors, challenges of resistance persist, necessitating alternative therapeutic approaches. The synthetic lethal interaction between WRN helicase inhibitio...
An Activator of Tailless' Repressor Function Stimulates Anti-Neurodegenerative Gene Expression [0.03%]
一种激活Tailless抑制功能的激活剂可促进抗神经退行性基因表达
Emily C Hank,Romy Busch,Úrsula López-García et al.
Emily C Hank et al.
The transcription factor tailless (TLX, NR2E1) is expressed in neuronal stem cells and retinal progenitor cells and is thought to maintain their self-renewal by balancing proliferation and differentiation. It is considered as a master regul...
Hongtao Zhao,Stefan Schiesser,Christian Tyrchan et al.
Hongtao Zhao et al.
Proteolysis-targeting chimeras (PROTACs) are heterobifunctional molecules that recruit an E3 ligase to a protein of interest, thereby promoting ubiquitin transfer and subsequent proteasomal degradation. Formation of the ternary complex is a...
DHODH Inhibitors Based on the Vidofludimus Scaffold Containing Carboxylic Acid Bioisosteres Exert a Superior Broad-Spectrum Antiviral Activity [0.03%]
基于Vidofludimus支架的DHODH抑制剂，含有羧酸生物电子等排体，具有优异的广谱抗病毒活性
Alexandra Herrmann,Friedrich Hahn,Christina Wangen et al.
Alexandra Herrmann et al.
Emerging and re-emerging viral infections demand the rapid development of broad-spectrum antivirals. Host-directed therapies targeting cellular metabolic pathways required for viral replication offer a promising strategy with a low risk of ...
A Hypoxia-Activated Photomolecular Glue with Synergistic Cyclin K Degradation and Phototherapy for Cancer Treatment [0.03%]
一种用于癌症治疗的低氧激活型光分子胶，可协同降解细胞周期蛋白K并进行光动力疗法
Shuai Li,Zhenzhen Tian,Yan Ma et al.
Shuai Li et al.
Cyclin K is overexpressed in multiple tumors and plays critical roles in tumorigenesis, making it a promising therapeutic target. Although the antitumor potential of Cyclin K-targeting molecular glues, their clinical application is limited ...
Lead Optimization of TgCDPK1 Inhibitors for the Treatment of Toxoplasmosis [0.03%]
治疗隐球病的TgCDPK1抑制剂的优化研究
Michael P Mannino,Anusha Gokanapalle,Shrushti Patil et al.
Michael P Mannino et al.
Toxoplasma gondii is an important opportunistic pathogen that infects many individuals and threatens the health of those with compromised immunity. Current therapies are unable to eradicate chronic infections and pose risks of adverse react...
Phosphorothioate-Free and Self-Interaction-Reduced Acyclic Nucleic Acids for Effective Antisense Oligonucleotide [0.03%]
不含磷硫酰基且自我相互作用减少的无环核酸类有效反义寡核苷酸
Yukiko Kamiya,Fuminori Sato,Kiyoka Sakashita et al.
Yukiko Kamiya et al.
Acyclic artificial nucleic acids, serinol nucleic acid (SNA) and acyclic l-threoninol nucleic acid (L-aTNA), are promising next-generation nucleic acid therapeutics with strong nuclease resistance and stable RNA hybridization, eliminating t...