SGC0946

Inhibitor of DOT1L

Structure

SERP Rating

In Cells

(4 ratings)

In Model Organisms

(0 ratings)

note: The Chemical Probes Portal only endorses compounds as chemical probes for use as specific and selective modulators of the proposed target if they receive three or more (3-4) stars.

Information

DOT1L

Inhibitor

Probe Availability:

In Vitro Validations

Uniprot ID: Q8TEK3

Target Class: Epigenetic

Target SubClass: Protein methyltransferase

Potency: KD

Potency Value: 0.06 nM

Potency Assay: SPR; IC50 = 0.3 nM in enzymatic assay

PDB ID for probe-target interaction (3D structure): 4ER6

Target aliases:

Histone-lysine N-methyltransferase, H3 lysine-79 s ...

In Cell Validations

In Vivo Data

No in Vivo Validations

Off-Target Selectivity Assesments

Potency assay (off target): Inactive against 12 protein methyltransferases and DNMT1

Probe Selectivity in Vitro:

No notable activity against 29 receptors from the Ricerca selectivity panel

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SERP ratings and comments

SERP Ratings

In Cell Rating

SERP Comments:

The inactive control SGC-0649 should only be used but at relatively low concentrations as it still retains some DOT1L activity (IC50 = 390 nM).

(last updated: 17 May 2016 )

SERP Ratings

In Cell Rating

SERP Comments:

SGC0649 is now available as a control compound. It is the 4-t-butylphenylamide as opposed to the urea in SGC0946

(last updated: 6 Jun 2016 )

SERP Ratings

In Cell Rating

SERP Comments:

This compound shows single digit nanomolar potency in cellular assays measuring reduction of H3K79me2. Downstream effects appear to require a higher concentration (1 - 5 micromolar). While concerns that this may be off-target activity are somewhat ameliorated by the clean selectivity profile, and similar activity for other probes, the availability of a close analogue without DOT1L activity as a negative control, and/or a DOT1L inhibitor of a different chemical class would add further confidence.

(last updated: 10 Jun 2016 )

SERP Ratings

In Cell Rating

SERP Comments:

The minimum time required for reduction of in-cell biomarker activity is 4 days for Molm13 MLL cells (but 7 days for A431 cells). The IC50 is ~ 3 nM for reduction of H3K79 methylation in A431 cells.

(last updated: 20 Jun 2016 )