Target Enabling Packages (TEPs)
Published February 4, 2019 | Version 2
Dataset Open

Human Mixed- Lineage Leukemia, Translocated to 1 (MLLT1); A Target Enabling Package

Authors/Creators

  • 1. Structural Genomics Consortium

Description

Overexpression of MLLT1 (also known as ENL, LTG19 and YEATS1) has recently been implicated as a driver of acute myeloid leukaemia (AML)(1, 2). Its epigenetic reader domain (dubbed YEATS domain) links histone acylation to gene expression via its role in the super elongation complex (SEC) (3) and its interaction with the histone methyl transferase DOT1L. Since epigenetic readers have been shown to be tractable targets for small molecule inhibitors, we have performed a library screen using a peptide displacement assay to identify inhibitors of MLLT1 interaction with acetylated histone tails. The screen yielded a potent hit and in further characterisation with biophysical methods it displayed a sub-micromolar KD for MLLT1 and its paralog MLLT3 (Also known as AF9) with no detectable binding to two other human YEATS proteins.

Notes

This document represents version 2 of the TEP datasheet and includes all updates on the project as of October 2020. For more information about TEPs and the TEP Programme, please visit https://thesgc.org/tep.

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MLLT1_TEP_datasheet_v2.pdf

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Additional details

Related works

Is part of
https://www.thesgc.org/tep (URL)

Funding

European Commission
ULTRA-DD - Unrestricted Leveraging of Targets for Research Advancement and Drug Discovery 115766
Wellcome Trust
A UK Hub to Catalyse Open Target Discovery. 106169