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KMI169

KMI169 : Inhibitor of N6AMT1

Structure

Information

  • N6AMT1
  • Inhibitor
  • 1 µM
  • Reviewer recommended concentration: 2 µM

In Vitro Validations

Uniprot ID: Q9Y5N5
Target Class: Epigenetic
Target SubClass: --
Potency: Kd
Potency Value: 25 nM
Potency Assay: Microscale thermophoresis (MST)
PDB ID for probe-target interaction (3D structure): --
Target aliases:
Methyltransferase N6AMT1, PRED28, KMT9, HEMK2, C21 ...

DOI Reference: 10.1038/s41467-023-44243-6

Uniprot ID: Q9Y5N5
Target Class: Epigenetic
Target SubClass: --
Potency: ΔTm
Potency Value: 12.5 K
Potency Assay: Fluorescence Thermal Shift Assay (FTSA)
PDB ID for probe-target interaction (3D structure): --
Target aliases:
Methyltransferase N6AMT1, PRED28, KMT9, HEMK2, C21 ...

DOI Reference: 10.1038/s41467-023-44243-6

Uniprot ID: Q9Y5N5
Target Class: Epigenetic
Target SubClass: --
Potency: IC50
Potency Value: 50 nM
Potency Assay: KMT9 methyltransferase inhibition assays
PDB ID for probe-target interaction (3D structure): --
Target aliases:
Methyltransferase N6AMT1, PRED28, KMT9, HEMK2, C21 ...

DOI Reference: 10.1038/s41467-023-44243-6

In Cell Validations

In Vivo Data

No in Vivo Validations

Off-Target Selectivity Assesments

Potency assay (off target): Selectivity of 1.5 uM KMI169 was assessed against the full panel of SET-domain and Rossmann-fold methyltransferases available at Reaction Biology. The results showed that the compound was selective with the potential exception of PRMT5. Upon performing enzymatic inhibition assays on PRMT5 up to 30uM, only 60% inhibition was observed. Outside target family: KINOMEscan screen against a panel of 97 representative kinases from different families confirmed selectivity of KMI169 for KMT9 at 10 uM.
Probe Selectivity in Cell:
No effect on symmetric dimethyl arginine in PC-3M cells, indicating no inhibition of PRMT5. No effect in CETSA with PRMT5.
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SERP ratings and comments

SERP Ratings

In Cell Rating

SERP Comments:

KMI169 and its control compound KMI169 Ctrl were well characterized in vitro in terms of potency, target engagement, and selectivity. Their cellular activities were demonstrated with multiple sets of GI50 data. The minor concern is the cellular IC50 for depleting the H4K12me biomarker, for which only one concentration of KMI169 and KMI169 Ctrl (500 nM) was assessed in a single cellular context. Ideally, the information should be more rigorously assessed in a dose-dependent manner and in multiple cellular contexts. As a result, the H4K12me biomarker of the efficiency of KMI169 should be used with caution regarding the cellular contexts.

(last updated: 13 Feb 2024 )

SERP Ratings

In Cell Rating

(last updated: 20 Feb 2024 )

SERP Ratings

In Cell Rating

SERP Comments:

KMI169 is a well characterised probe with data from biophysical, biochemical and cellular assays which together with the inactive control compound provide valuable tools to enable exploration of KMT9 biology. The methyltransferase profiling demonstrates impressive selectivity, however during analysis of any cellular phenotypic data it is worth considering that other untested enzymes for which SAM is a substrate could also be sensitive.

(last updated: 5 Mar 2024 )