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UNC100013

UNC100013 : Covalent Inhibitor of SETDB1

Structure

Information

  • SETDB1
  • Covalent Inhibitor
  • up to 30 uM considering the low cell permeability

In Vitro Validations

Uniprot ID: Q15047
Target Class: Enzyme
Target SubClass: Methyltransferase
Potency: IC50
Potency Value: 57 ± 13 nM
Potency Assay: TR-FRET
PDB ID for probe-target interaction (3D structure): 9CUW
Target aliases:
Histone-lysine N-methyltransferase SETDB1, KMT1E, ...

DOI Reference: 10.1038/s41467-025-57005-3

Uniprot ID: Q15047
Target Class: Enzyme
Target SubClass: Methyltransferase
Potency: Ki
Potency Value: 60 ± 24 nM
Potency Assay: TR-FRET displacement assay (kinact/KI of 1.04 × 10^6 M−1 s−1)
PDB ID for probe-target interaction (3D structure): --
Target aliases:
Histone-lysine N-methyltransferase SETDB1, KMT1E, ...

DOI Reference: 10.1038/s41467-025-57005-3

Uniprot ID: Q15047
Target Class: Enzyme
Target SubClass: Methyltransferase
Potency: ΔTm
Potency Value: 7.0 ± 0.1 K
Potency Assay: DSF
PDB ID for probe-target interaction (3D structure): --
Target aliases:
Histone-lysine N-methyltransferase SETDB1, KMT1E, ...

DOI Reference: 10.1038/s41467-025-57005-3

Uniprot ID: Q15047
Target Class: Enzyme
Target SubClass: Methyltransferase
Potency: IC50
Potency Value: 27 ± 5 nM
Potency Assay: Nucleosome TR-FRET
PDB ID for probe-target interaction (3D structure): --
Target aliases:
Histone-lysine N-methyltransferase SETDB1, KMT1E, ...

DOI Reference: 10.1038/s41467-025-57005-3

Uniprot ID: Q15047
Target Class: Enzyme
Target SubClass: Methyltransferase
Potency: IC50
Potency Value: 70 ± 10 nM
Potency Assay: Fluorescence Polarization assay
PDB ID for probe-target interaction (3D structure): --
Target aliases:
Histone-lysine N-methyltransferase SETDB1, KMT1E, ...

DOI Reference: 10.1038/s41467-025-57005-3

In Cell Validations

In Vivo Data

No in Vivo Validations

Off-Target Selectivity Assesments

Potency assay (off target): 33 methyltransferases tested for off-target activity of UNC10013 at 10 uM using a radiometric methyltransferase assay. UNC10013 was at least 100-fold selective against the eight Kme readers tested, which included various Kme sub-families such as Tudor domains, chromodomains, and PHD domains.
Probe Selectivity in Vitro:
UNC10013 is selective for the binding of the 3TD of SETDB1 by 30-fold relative to SETD2 inhibition (IC50 = 0.8 ± 0.1 µM), and 48-fold relative to PRMT1 inhibition (IC50 = 1.3 ± 0.1 µM).
Potency assay, off target (cells): Cysteine reactivity of 23,149 detected cysteines after treatment of MCF-7 cell lysate with 10 µM of UNC10013 was analysed. Two cysteines showed significant cysteine reactivity, SETDB1 Cys385 and NCK2 Cys144.
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SERP ratings and comments

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