UNC1215

UNC1215 : Inhibitor 2:2 dimer formation of L3MBTL3

Structure

SERP Rating

In Cells

(3 ratings)

In Model Organisms

(1 ratings)

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Information

L3MBTL3

2:2 dimer formation

100 nM - 1 uM

DOI - 10.1038/nchembio.1157

Probe Availability:

In Vitro Validations

Uniprot ID: Q96JM7

Target Class: Epigenetic

Target SubClass: Malignant brain tumor Reader

Potency: Kd

Potency Value: 120 nM

Potency Assay: ITC

PDB ID for probe-target interaction (3D structure): 4FL6

Target aliases:

Lethal(3)malignant brain tumor-like protein 3, MBT ...

DOI Reference: 10.1038/nchembio.1157

Uniprot ID: Q96JM7

Target Class: Epigenetic

Target SubClass: Malignant brain tumor Reader

Potency: IC50

Potency Value: 40 nM

Potency Assay: Alpha screen methylated histone peptide competition assay

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

Target aliases:

Lethal(3)malignant brain tumor-like protein 3, MBT ...

DOI Reference: 10.1038/nchembio.1157

In Cell Validations

In Vivo Data

No in Vivo Validations

Off-Target Selectivity Assesments

Potency end-point : IC50 L3MBTL1 2 uM

Potency assay (off target): UNC1215 is >50-fold selective for L3MBtL3 in an alpha screen against Kme readers proteins. No activity to 30 uM was detected against UHRF1, CBX7, JARID1A.

Probe Selectivity in Vitro:

In an array of 250 chromatin-associated effector proteins (Cador 5.0), UNC1215 bound to 6 proteins (L3MBTL1, PHF20, PHF20L1, 53BP1, SPF30, MRG15). PHF20 KD (1) 9.4 uM, (2) 5.6 uM. UNC1215 was inactive against Protein methyltransferases (<50% at 250 uM) in a radiometric assay. Activity against GPCRs and ion channels (NIMH PDSP selectivity panel) was negligible except: M1 muscarinic receptor Ki= 97 nM, IC50 = 3.5 uM and M2 muscarinic receptor Ki = 72 nM, IC50 >30 uM. In a panel of 50 kinases, UNC1215 inhibited 49 kinases by <15% at 10 uM, and 64% of FLT3 activity at 10 uM.

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SERP ratings and comments

SERP Ratings

In Cell Rating

(last updated: 14 Jun 2016 )

SERP Ratings

In Cell Rating

SERP Comments:

This probe seems to have a very nice selectivity towards L3MBTL3. UNC1215 is nontoxic at concentration well above the EC50.

(last updated: 22 Jun 2016 )

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

As of June 2016, this is the first and only potent and selective inhibitor of L3MBTL3 with activity in cells. This looks like a good compound to probe this target's disease relevance and biology. The authors have characterized its off target activities as comprehensively as can be expected, including kinases, secondary pharmacology, epigenetic enzyme panels and cellular target pull-down experiments, and the data supports UNC1215 as a potent and selective inhibitor.

(last updated: 23 Jun 2016 )