BAY-6035 A potent, peptide-competitive chemical probe for SMYD3

This probe is available from Sigma, Tocris and Cayman Chemical.

For any inquiries please contact proberequests@thesgc.org.

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Overview

BAY-6035

BAY-444

A collaboration between Bayer AG and the SGC has resulted in the discovery of BAY-6035, a potent, peptide-competitive chemical probe for SMYD3. BAY-6035 has a unique chemotype relative to the published SMYD3 inhibitor, EPZ031686. BAY-6035 inhibits in vitro methylation of MEKK2 peptide with IC50 = 88 nM and has more than 100-fold selectivity over other histone methyltransferases. BAY-6035 inhibits the methylation of MEKK2 in cells with IC50 = 70 nM. A control compound, BAY-444, has also been developed. BAY-444 inhibits the in vitro methylation of MEKK2 with IC50 = 23 micromolar.

https://doi.org/10.1177/24725552211019409

Properties

BAY-6035

BAY-444
(negative control)

Physical and chemical properties for BAY-6035
Molecular weight	396.2
Molecular formula	C22H28N4O3
IUPAC name	6-((3-aza-bicyclo[3.1.0]hexan-3-yl)-formyl)-10-((2-cyclopropyl-ethylamino)-formyl)-5-methyl-2,6-diaza-bicyclo[5.4.0]undeca-1(7),8,10-trien-3-one
MollogP	2.011
PSA	66.79
No. of chiral centres	3
No. of rotatable bonds	7
No. of hydrogen bond acceptors	6
No. of hydrogen bond donors	2

Physical and chemical properties for BAY-444 (Negative Control)
Molecular weight	410.2
Molecular formula	C23H30N4O3
IUPAC name	6-((3-aza-bicyclo[3.1.0]hexan-3-yl)-formyl)-10-(((2-cyclopropyl-ethyl)-methyl-amino)-formyl)-5-methyl-2,6-diaza-bicyclo[5.4.0]undeca-1(7),8,10-trien-3-one
MollogP	2.208
PSA	58.66
No. of chiral centres	3
No. of rotatable bonds	7
No. of hydrogen bond acceptors	6
No. of hydrogen bond donors	1

SMILES:
BAY-6035: C[C@H]1CC(Nc2cc(ccc2N1C(N1CC2CC2C1)=O)C(NCCC1CC1)=O)=O
BAY-444: C[C@@H]1CC(Nc2cc(ccc2N1C(N1CC2CC2C1)=O)C(N(C)CCC1CC1)=O)=O

InChI:
BAY-6035: InChI=1S/C22H28N4O3/c1-13-8-20(27)24-18-10-15(21(28)23-7-6-14-2-3-14)4-5-19(18)26(13)22(29)25-11-16-9-17(16)12-25/h4-5,10,13-14,16-17H,2-3,6-9,11-12H2,1H3,(H,23,28)(H,24,27)/t13-,16?,17?/m0/s1

BAY-444: InChI=1S/C23H30N4O3/c1-14-9-21(28)24-19-11-16(22(29)25(2)8-7-15-3-4-15)5-6-20(19)27(14)23(30)26-12-17-10-18(17)13-26/h5-6,11,14-15,17-18H,3-4,7-10,12-13H2,1-2H3,(H,24,28)/t14-,17?,18?/m1/s1)

InChIKey:
BAY-6035: CKFRXCBNKKOFGO-IGEOTXOUSA-N
BAY-444: FNTARNKIMWWTFZ-RWBZWWBESA-N