Identification of potent and reversible piperidine carboxamides that are species-selective orally active proteasome inhibitors to treat malaria [0.03%]
用于治疗疟疾的高效可逆的哌啶类羧酸铵亚型特异性口服活性蛋白酶抑制剂的鉴定
Aloysus Lawong,Suraksha Gahalawat,Sneha Ray et al.
Aloysus Lawong et al.
Malaria remains a global health concern as drug resistance threatens treatment programs. We identified a piperidine carboxamide (SW042) with anti-malarial activity by phenotypic screening. Selection of SW042-resistant Plasmodium falciparum ...
Dissecting the neuroprotective interaction between the BH4 domain of BCL-w and the IP3 receptor [0.03%]
BH4结构域与IP3受体之间的神经保护作用机制研究
Sophia X Tang,Christina M Camara,Joy A Franco et al.
Sophia X Tang et al.
BCL-w is a BCL-2 family protein that promotes cell survival in tissue- and disease-specific contexts. The canonical anti-apoptotic functionality of BCL-w is mediated by a surface groove that traps the BCL-2 homology 3 (BH3) α-helices of pr...
Prephenate decarboxylase: An unexplored branchpoint to unusual natural products [0.03%]
对羟苯甲酸脱羧酶：一种产生非常规天然产物的未开发途径分支点
Mostafa Hagar,Raymond J Andersen,Katherine S Ryan
Mostafa Hagar
Prephenate decarboxylases are a small family of enzymes which initiate a specialized divergence from the shikimate pathway, where prephenate (2) is decarboxylated without aromatization. In addition to effecting a challenging chemical transf...
Targeting type I DED interactions at the DED filament serves as a sensitive switch for cell fate decisions [0.03%]
靶向DED互作丝状结构上的一型DED相互作用可作为细胞命运决定的敏感开关
Corinna König,Nikita V Ivanisenko,Laura K Hillert-Richter et al.
Corinna König et al.
Activation of procaspase-8 in the death effector domain (DED) filaments of the death-inducing signaling complex (DISC) is a key step in apoptosis. In this study, a rationally designed cell-penetrating peptide, DEDid, was engineered to mimic...
A highly potent bi-thiazole inhibitor of LOX rewires collagen architecture and enhances chemoresponse in triple-negative breast cancer [0.03%]
一种高效的双噻唑LOX抑制剂可重构三阴性乳腺癌中的胶原蛋白结构并增强其化学敏感性
Metin Cetin,Ozge Saatci,Abdol-Hossein Rezaeian et al.
Metin Cetin et al.
Lysyl oxidase (LOX) is upregulated in highly stiff aggressive tumors, correlating with metastasis, resistance, and worse survival; however, there are currently no potent, safe, and orally bioavailable small molecule LOX inhibitors to treat ...
Parker E Deal,Haerim Lee,Abhisek Mondal et al.
Parker E Deal et al.
K2P potassium channels regulate excitability by affecting cellular resting membrane potential in the brain, cardiovascular system, immune cells, and sensory organs. Despite their important roles in anesthesia, arrhythmia, pain, hypertension...
Hanna Karvonen,Neil Vasan
Hanna Karvonen
In their recent paper published in Nature, Luo et al.1 investigate the cancer-cell-intrinsic roles of the PI3Kγ complex in leukemia. Their findings pinpoint PI3Kγ inhibition as a possible novel treatment avenue for a subset of acute leuke...
Mario J Avellaneda,Michael Sixt
Mario J Avellaneda
In a recent issue of Cell, Zhang et al.1 demonstrate that mechanical features of a solid tumor can drive T cells into dysfunctionality and identify pathways that revert this "exhausted" state. ...
CBLs downregulation foretells T cell ubiquitination leading to autoimmunity [0.03%]
CBLs下调预示T细胞泛素化导致自身免疫反应
Aurobind Vidyarthi,Joe Craft
Aurobind Vidyarthi
In a study published in the July issue of Immunity, Li et al.1 demonstrate that expression of the E3 ubiquitin ligases CBL and CBL-B is downregulated in Tfh cells in SLE with Tfh cell expansion and autoimmunity. This leads to reduced ubiqui...
A new light on PLCβ! [0.03%]
PLCβ的全新亮点！
Sithurandi Ubeysinghe,Waruna Thotamune,Ajith Karunarathne
Sithurandi Ubeysinghe
In this issue of Cell Chemical Biology, Kim et al.1 present a novel optogenetic tool, opto-PLCβ, to control PLCβ signaling optically. In addition to eliciting PIP2 hydrolysis and downstream signaling in cells, opto-PLCβ also enabled prob...