Delving into the Latest Updates on LEM-06 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms-

Target

NSD2

Action

inhibitors

Mechanism

NSD2 inhibitors(nuclear receptor binding SET domain protein 2 inhibitors)

Therapeutic Areas

NeoplasmsImmune System DiseasesHemic and Lymphatic Diseases

Active Indication-

Inactive Indication

Multiple Myeloma

Originator Organization

Kyungpook National University

Active Organization-

Inactive Organization

Kyungpook National University

License Organization-

Drug Highest PhasePendingPreclinical

First Approval Date-

Regulation-

Structure/Sequence

Molecular FormulaC29H38N4O3

InChIKeyWLGRGOGJTIXJGZ-VWNXMTODSA-N

CAS Registry2200311-00-6

BACKGROUNDMultiple myeloma SET domain (MMSET)/nuclear receptor binding SET domain 2 (NSD2) is a lysine histone methyltransferase (HMTase) and bona fide oncoprotein found aberrantly expressed in several cancers, suggesting potential role for novel therapeutic strategies. In particular, MMSET/NSD2 is emerging as a target for therapeutic interventions against multiple myeloma, especially t(4;14) myeloma that is associated with a significantly worse prognosis than other biological subgroups. Multiple myeloma is the second most common hematological malignancy in the United States, after non-Hodgkin lymphoma and remains an incurable malignancy. Thus, effective therapeutic strategies are greatly needed. HMTases inhibitors are scarce and no NSDs inhibitors have been isolated.METHODSWe used homology modeling, molecular modeling simulations, virtual ligand screening, computational chemistry software for structure-activity relationship and performed in vitro H3K36 histone lysine methylation inhibitory assay using recombinant human NSD2-SET and human H3.1 histone.RESULTSHere, we report the discovery of LEM-06, a hit small molecule inhibitor of NSD2, with an IC50 of 0.8 mM against H3K36 methylation in vitro.CONCLUSIONSWe propose LEM-06 as a hit inhibitor that is useful to further optimize for exploring the biology of NSD2. LEM-06 derivatives may pave the way to specific NSD2 inhibitors suitable for therapeutic efforts against malignancies.

100 Deals associated with LEM-06

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