Last update 01 Nov 2024

MAP3K13

Last update 01 Nov 2024

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

DN-1289

Target

MAP3K12 x MAP3K13

Mechanism

MAP3K12 inhibitors [+1]

Active Org.

Denali Therapeutics, Inc.

Originator Org.

Denali Therapeutics, Inc.

Active Indication

Amyotrophic Lateral Sclerosis

Inactive Indication-

Drug Highest PhasePreclinical

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

170

Literatures (Medical) associated with MAP3K13

12 Sep 2024·Journal of Medicinal Chemistry

Selective Degradation of MLK3 by a Novel CEP1347-VHL-02 PROTAC Compound Limits the Oncogenic Potential of TNBC

Article

Author: Marusiak, Anna A. ; Sabbasani, Venkata R. ; Truong, Vi Nguyen-Phuong ; Swenson, Rolf E. ; Serwa, Remigiusz ; Łomiak, Michał ; Brognard, John ; Torres-Ayuso, Pedro ; Mehlich, Dawid ; Karpińska, Kamila ; Wróbel, Katarzyna

Triple-negative breast cancer (TNBC) is associated with poor prognosis because of the lack of effective therapies. Mixed-lineage protein kinase 3 (MLK3) is a protein that is often upregulated in TNBC and involved in driving the tumorigenic potential of cancer cells. Here, we present a selective MLK3 degrader, CEP1347-VHL-02, based on the pan-MLK inhibitor CEP1347 and a ligand for E3 ligase von Hippel-Lindau (VHL) by employing proteolysis-targeting chimera (PROTAC) technology. Our compound effectively targeted MLK3 for degradation via the ubiquitin-proteasome system in several cell line models but did not degrade other MLK family members. Furthermore, we showed that CEP1347-VHL-02 robustly degraded MLK3 and inhibited its oncogenic activity in TNBC, measured as a reduction of clonogenic and migratory potential, cell cycle arrest, and the induction of apoptosis in MDA-MB-468 cells. In conclusion, we present CEP1347-VHL-02 as a novel MLK3 degrader that may be a promising new strategy to target MLK3 in TNBC.

01 May 2024·Ear, Nose & Throat JournalQ4 · MEDICINE

Head and Neck Malignant Paragangliomas: Experience from a Single Institution

Q4 · MEDICINE

ArticleOA

Author: Han, Demin ; Ding, Yiming ; Chen, Xiaohong ; Wang, Shaozhong ; Li, Lifeng

Objectives: To summarize the clinicopathological and genetic features of malignant paragangliomas in head and neck cancer and to explore the appropriate treatment options for this rare lesion. Methods: Six patients harboring head and neck malignant paraganglioma from Beijing Tongren Hospital were retrospectively reviewed. The clinicopathological characteristics, gene mutations, and prognosis of these patients were analyzed. Results: Of these 6 patients, 3 were male and 3 were female; 4 patients harbored malignant carotid body tumors, and two had malignant vagal paragangliomas. Three patients had cervical lymph node metastasis, two presented with lung and bone metastasis, and 1 had lung and liver metastasis. Of the 6 patients, four underwent surgical resection, and the other two patients denied surgery and instead received chemotherapy with paclitaxel, ifosfamide, and dacarbazine. These 2 patients with vagal paraganglioma received postoperative radiotherapy. All 6 patients are still alive at the present time, with a median follow-up time of 66 months. Positive Ki-67 expression in tumor tissue ranged from 1% to 40%. Genetic mutations in SDHD, SDHB, ATR, and MAP3K13 were identified in 4 patients. Conclusions: After comprehensive treatment, head and neck malignant paraganglioma can attain a favorable prognosis. Genetic mutations are commonly detected in patients with malignant paragangliomas. This study also identified mutations in ATR and MAP3K13 in these patients.

01 Apr 2024·International Journal of Pediatric Otorhinolaryngology

Correlation of patient reported outcome measures with endoscopic findings in pediatric chronic adenoiditis and chronic rhinosinusitis

Article

Author: Ramadan, Hassan H ; McArdle, Erica ; Makary, Chadi A ; Coutinho, Dominic ; Shetty, Sameer

BACKGROUNDStudies in adult chronic rhinosinusitis (CRS) showed poor correlation between patient reported outcome measures (PROMs) and objective findings. Our goal is to study the correlation between the sinus and nasal quality of life (SN-5) and the 22-items sinonasal outcome test (SNOT-22) surveys with endoscopy findings in children with chronic adenoiditis (CA) and CRS.METHODSCross-sectional study of all pediatric patients (age 2-18) presenting for CA or CRS was performed. Patients and caregivers were asked to fill the SN-5 and SNOT-22 questionnaires at initial and follow up visits. Demographics and comorbidities were collected. Objective findings included endoscopy Modified Lund-Kennedy (MLK) scores and adenoid tissue size.RESULTS124 children were included, with mean age of 9.9 years (SD = 4.8) and 46.8% female. 36.3% had allergic rhinitis, 23.4% had asthma, and 4% had obstructive sleep apnea. Moderate correlation was found between the rhinologic domain of SNOT-22 and MLK scores (r = 0.36, p = 0.001) and between SN5 scores and adenoid size in all patients (r = 0.39, p < 0.001). SNOT-22 scores showed moderate correlation with adenoid size (r = 0.42, p < 0.001) more specifically in CA patients (r = 0.54, p < 0.001). The correlation of SN5 and MLK scores were higher in children with allergic rhinitis or asthma. The correlation between SN5 and adenoid size was lower in children with allergic rhinitis or asthma.CONCLUSIONThere is discrepancy between the subjective measures and the objective findings in children with CA or CRS. The physical exam findings may not reflect the effect of CRS on the quality of life of children.

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MAP3K13

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