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Last update 08 May 2025

MAP3K13

Last update 08 May 2025

Basic Info

Synonyms

Leucine zipper-bearing kinase, LZK, MAP3K13

+ [4]

Introduction

Activates the JUN N-terminal pathway through activation of the MAP kinase kinase MAP2K7. Acts synergistically with PRDX3 to regulate the activation of NF-kappa-B in the cytosol. This activation is kinase-dependent and involves activating the IKK complex, the IKBKB-containing complex that phosphorylates inhibitors of NF-kappa-B.

Drugs associated with MAP3K13

US20230382904

Patent Mining

Target

MAP3K13

Mechanism-

Active Org.

The Johns Hopkins University

Originator Org.

The Johns Hopkins University

Active Indication

Cardiovascular Diseases [+5]

Inactive Indication-

Drug Highest PhaseDiscovery

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

CN118878535

Patent Mining

Target

MAP3K13 x RIPK1

Mechanism

MAP3K13 inhibitors [+1]

Active Org.

Chengdu Ori Pharmaceutical Co., Ltd.

Originator Org.

Chengdu Ori Pharmaceutical Co., Ltd.

Active Indication

Autoimmune Diseases [+3]

Inactive Indication-

Drug Highest PhaseDiscovery

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

US20250032489

Patent Mining

Target

MAP3K13

Mechanism

MAP3K13 inhibitors

Active Org.

Government of the United States of America

Originator Org.

Government of the United States of America

Active Indication

Neoplasms

Inactive Indication-

Drug Highest PhaseDiscovery

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with MAP3K13

100 Translational Medicine associated with MAP3K13

0 Patents (Medical) associated with MAP3K13

169

Literatures (Medical) associated with MAP3K13

01 Mar 2025·Journal of Biological Chemistry

Discovery of potent and selective PROTACs for the protein kinase LZK for the treatment of head and neck cancer

Article

Author: Marusiak, Anna ; Bergman, Knickole L ; Woodroofe, Carolyn C ; Katerji, Meghri ; Swenson, Rolf E ; Karpińska, Kamila ; Serwa, Remigiusz ; Brognard, John F ; Rubin, Maxine R ; Funk, Amy L ; Lindberg, Eric ; Nyswaner, Katherine

Leucine zipper-bearing kinase (LZK) is overexpressed in 20% of head and neck squamous cell carcinoma (HNSCC) cases and has emerged as a promising therapeutic target in this cancer subtype. LZK promotes HNSCC survival and proliferation by stabilizing c-MYC and GOF-p53 in kinase-dependent and -independent manners, respectively. Herein, we developed a new series of LZK degraders utilizing proteolysis-targeting chimera (PROTAC) technology by modulating the linker region or LZK warhead of LZK-targeting PROTAC-21A, previously developed by our lab. Among the 27 PROTACs synthesized and tested, PROTAC 17 was found to be the most potent, degrading LZK at 250 nM and suppressing HNSCC viability at 500 nM. In summary our lead PROTAC effectively targeted LZK for proteasomal degradation and inhibited oncogenic activity in HNSCC cell lines with amplified LZK.

11 Feb 2025·Science Signaling

Targeting c-MYC and gain-of-function p53 through inhibition or degradation of the kinase LZK suppresses the growth of HNSCC tumors

Article

Author: Nyswaner, Katherine ; Xu, Xin ; Ahel, Ivan ; Marusiak, Anna A. ; Cappell, Steven D. ; Robinson, Christina M. ; Edwards, Zoe C. ; Chen, Li ; James, Amy ; Lindberg, Eric ; Rubin, Maxine R. ; Doroshow, James H. ; Gough, Nancy R. ; Katerji, Meghri ; Trotter, Eleanor W. ; Karpińska, Kamila ; Funk, Amy L. ; Bergman, Knickole L. ; Chang, Ting-Chia ; Karim, Baktiar O. ; Dash, Sweta ; Woodroofe, Carolyn C. ; Difilippantonio, Simone ; Ries, Amy L. ; Afifi, Marwa ; Swenson, Rolf E. ; Brognard, John

The worldwide annual frequency and lethality of head and neck squamous cell carcinoma (HNSCC) is not improving, and thus, new therapeutic approaches are needed. Approximately 70% of HNSCC cases have either amplification or overexpression of MAP3K13 , which encodes the kinase LZK. Here, we found that LZK is a therapeutic target in HNSCC and that small-molecule inhibition of its catalytic function decreased the viability of HNSCC cells with amplified MAP3K13 . Inhibition of LZK suppressed tumor growth in MAP3K13 -amplified xenografts derived from HNSCC patients. LZK stabilized the transcription factor c-MYC through its kinase activity and gain-of-function mutants of p53 in a kinase-independent manner. We designed a proteolysis-targeting chimera (PROTAC) that induced LZK degradation, leading to decreased abundance of both c-MYC and gain-of-function p53, and reduced the viability of HNSCC cells. Our findings demonstrate that LZK-targeted therapeutics, particularly PROTACs, may be effective in treating HNSCCs with MAP3K13 amplification.

01 Feb 2025·The Plant Journal

Nitrate activates an MKK3‐dependent MAPK module via NLP transcription factors in Arabidopsis

Article

Author: Krapp, Anne ; Marmagne, Anne ; Boudsocq, Marie ; Colcombet, Jean ; Chardin, Camille ; Brehaut, Virginie ; Schenk, Sebastian T.

SUMMARYPlant responses to nutrient availability are critical for plant development and yield. Nitrate, the major form of nitrogen in most soils, serves as both a nutrient and signaling molecule. Nitrate itself triggers rapid, major changes in gene expression, especially via nodule inception (NIN)‐like protein (NLP) transcription factors, and stimulates protein phosphorylation. Mitogen‐activated protein kinase (MAPK)‐related genes are among the early nitrate‐responsive genes; however, little is known about their roles in nitrate signaling pathways. Here, we show that nitrate resupply to nitrogen‐depleted Arabidopsis (Arabidopsis thaliana) plants triggers, within minutes, an MAPK cascade that requires NLP‐dependent transcriptional induction of mitogen‐activated protein kinase kinase kinase 13 (MAP3K13) and MAP3K14 and that the MAPK cascade is composed of MKK3 and likely C‐clade MAPKs (MPK1/2/7/14). Importantly, nitrate reductase‐deficient mutants exhibited nitrate‐induced MPK7 activities comparable to those observed in wild‐type plants, indicating that nitrate itself is the signal that stimulates the cascade. We show that the modified expression of MAP3K13 and MAP3K14 affects nitrate‐stimulated BT2 expression and modulates plant responses to nitrogen availability, such as nitrate uptake and senescence. Our finding that an MAPK cascade involving MAP3K13 and MAP3K14 functions in the complex regulatory network governing responses to nitrate availability will guide future strategies to optimize plant responses to nitrogen fertilization and nitrogen use efficiency.

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MAP3K13

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