Brenetafusp (IMC-F106C) is an immune-mobilizing monoclonal T cell receptor against cancer (ImmTAC ®) designed for the treatment of cancers positive for the tumor-associated antigen PRAME. This is a first-in-human trial designed to evaluate the safety and efficacy of brenetafusp in adult patients who have the appropriate HLA-A2 tissue marker and whose cancer is positive for PRAME.

Start Date25 Feb 2020

Sponsor / Collaborator

Immunocore Ltd.

100 Clinical Results associated with MLK subfamily

100 Translational Medicine associated with MLK subfamily

0 Patents (Medical) associated with MLK subfamily

931

Literatures (Medical) associated with MLK subfamily

15 Jan 2025·Journal of Agricultural and Food Chemistry

bta-miR-484 Inhibits Bovine Intramuscular Adipogenesis by Regulating Mitotic Clonal Expansion via the MAP3K9/JNK/CCND1 Axis

Article

Author: Yang, Zhimei ; Zan, Linsen ; Sun, Meijun ; Zhang, Dianqi ; Ma, Xinhao ; Mei, Chugang ; Gao, Ni

Intramuscular fat (IMF) content is a critical indicator of the beef nutritional value and flavor. In this study, we focused on bta-miR-484, a microRNA that is differentially expressed during the adipogenic differentiation of bovine intramuscular adipocytes and is negatively correlated with the IMF content across different cattle breeds. Our findings demonstrate that bta-miR-484 inhibits adipogenic differentiation without altering the fatty acid composition of bovine intramuscular adipocytes. miRNA pull-down and dual-luciferase reporter assays confirmed that MAP3K9 is a target gene of bta-miR-484. Furthermore, bta-miR-484 suppresses the JNK signaling pathway by targeting MAP3K9, leading to decreased CCND1 expression, which impedes the mitotic clonal expansion (MCE) process and inhibits intramuscular adipocyte differentiation. In summary, this study uncovers a novel mechanism by which bta-miR-484 regulates bovine IMF content and provides the first exploration of MCE during intramuscular adipocyte adipogenic differentiation. These findings offer valuable theoretical insights into beef cattle breeding and molecular improvements.

09 Jan 2025·Journal of Medicinal Chemistry

Design, Synthesis, and Biochemical Evaluation of Novel MLK3 Inhibitors: A Target Hopping Example

Article

Author: Müller, Susanne ; Sander, Pascal ; Elson, Lewis ; Schwalm, Martin P. ; Sievers-Engler, Adrian ; Albrecht, Wolfgang ; Lämmerhofer, Michael ; Laufer, Stefan A. ; Masberg, Benedikt ; Rasch, Alexander ; Knapp, Stefan ; Krämer, Andreas ; Selig, Roland

The human kinome has tremendous medical potential. In the past decade, mixed-lineage protein kinase 3 (MLK3) has emerged as an interesting and druggable target in oncogenic signaling. The important role of MLK3 has been demonstrated in several types of cancer. In a target hopping example we started with the focal adhesion kinase (FAK) inhibitor PF-431396 (10), which shows off-target activity toward MLK3. We were able to develop highly active compounds in the single digit nanomolar range for MLK3. Furthermore, we achieved a dramatic shift in selectivity from FAK to MLK3. Here we present a new chemical class of MLK3 inhibitors, including our lead compound 37 with an outstanding IC₅₀ value of <1 nM in a biochemical MLK3 assay while simultaneously exhibiting kinome-wide selectivity.

01 Jan 2025·International Journal of Biological Macromolecules

Bta-miR-484 regulates proliferation and apoptosis of bovine intramuscular preadipocytes via targeting MAP3K9 to inhibit the JNK signaling pathway

Article

Author: Yang, Zhimei ; Zan, Linsen ; Sun, Meijun ; Zhang, Dianqi ; Ma, Xinhao ; Mei, Chugang

Intramuscular fat (IMF) plays a crucial role in enhancing the tenderness, flavor, and juiciness of beef, making the increase of IMF content a significant objective in beef breeding. A key factor influencing IMF levels is the number of intramuscular preadipocytes. Previous studies have indicated a correlation between bta-miR-484 and IMF content. In this study, we found that bta-miR-484 is differentially expressed during the proliferation of intramuscular preadipocytes. Our research identified that bta-miR-484 targets MAP3K9, revealing a novel mechanism for regulating both proliferation and apoptosis via the JNK signaling pathway. Functional gain and loss experiments demonstrated that bta-miR-484 inhibits the transition of bovine intramuscular preadipocytes from the G0/G1 phase to the S phase, and significant increase the proportion of early apoptotic cells. Additionally, miRNA pulldown and luciferase reporter assays confirmed MAP3K9 as the target gene of bta-miR-484. Furthermore, rescue experiments indicated that bta-miR-484 mediates its effects on proliferation and apoptosis through the MAP3K9/JNK/CCND1 and MAP3K9/JNK/BCL2 axes. These findings suggest that bta-miR-484 is a non-coding RNA that inhibits the proliferation and promotes the apoptosis of intramuscular preadipocytes, indicating that treatment with bta-miR-484 may offers a novel strategy for enhancing IMF content.

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