Delving into the Latest Updates on CEP1347-VHL-02 with Synapse

Overview

Basic Info

Drug Type

Proteolysis-targeting chimeras (PROTAC)

Synonyms-

Target

MAP3K11

Action

inhibitors

Mechanism

MAP3K11 inhibitors(Mitogen-activated protein kinase kinase kinase 11 inhibitors)

Therapeutic Areas

Neoplasms

Active Indication

Neoplasms

Inactive Indication-

Originator Organization

National Institutes of HealthInstytut Immunologii i Terapii Doswiadczalnej

Active Organization

Instytut Immunologii i Terapii Doswiadczalnej

National Institutes of Health

Inactive Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

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.

100 Deals associated with CEP1347-VHL-02

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Neoplasms	Preclinical	Poland	National Institutes of Health	17 Oct 2024
Neoplasms	Preclinical	Poland	Instytut Immunologii i Terapii Doswiadczalnej	17 Oct 2024
Neoplasms	Preclinical	United States	Instytut Immunologii i Terapii Doswiadczalnej	17 Oct 2024
Neoplasms	Preclinical	United States	National Institutes of Health	17 Oct 2024