Hexanoic acid, 3-[[(1,1-dimethylethoxy)carbonyl]amino]-2-hydroxy-5-methyl-, (3aS,4R,7R,8aS,9S,10aR,12aS,12bR,13S,13aS)-7,12a-bis(acetyloxy)-13-(benzoyloxy)-3a,4,7,8,8a,9,10,10a,12,12a,12b,13-dodecahyd ro-9-hydroxy-5,8a,14,14-tetramethyl-2,8-dioxo-6,13a-methano-13aH-oxeto[2'',3'':5',6']benzo[1',2':4,5]cyclodeca[1,2-d]-1,3-dioxol-4-yl ester, (2R,3S)- Chemical Properties

Boiling point:

929.7±65.0 °C(Predicted)

Density 

1.36±0.1 g/cm3(Predicted)

solubility 

Soluble in DMSO

pka

11.75±0.46(Predicted)

Hexanoic acid, 3-[[(1,1-dimethylethoxy)carbonyl]amino]-2-hydroxy-5-methyl-, (3aS,4R,7R,8aS,9S,10aR,12aS,12bR,13S,13aS)-7,12a-bis(acetyloxy)-13-(benzoyloxy)-3a,4,7,8,8a,9,10,10a,12,12a,12b,13-dodecahyd ro-9-hydroxy-5,8a,14,14-tetramethyl-2,8-dioxo-6,13a-methano-13aH-oxeto[2'',3'':5',6']benzo[1',2':4,5]cyclodeca[1,2-d]-1,3-dioxol-4-yl ester, (2R,3S)- Usage And Synthesis

Biological Activity

bay-598 is a aminopyrazoline-based in-vivo probe for smyd2.smyd2 is a catalytic set domain containing protein methyltransferase to monomethylate lysine residues on histone and nonhistone proteins. the overexpression of smyd2 has been found in cancer cell lines and also in various cancer patients.

in vitro

previous data suggest that bay-598 is a peptide-competitive, sam-uncompetitive inhibitor of smyd2 methyltransferase activity, binding to the smyd2 sam substrate complex. bay-598 was tested on a panel of 32 additional methyltransferases, and the results showed that bay-598 displayed >100-fold selectivity for smyd2, with very weak activity for the closest related methyltransferase smyd3. though bay-598 proved to be active for both smyd2 inhibition and par1 antagonism, there was still a greater than 50-fold selectivity for smyd2 relative to par1 [1].

in vivo

in animal study, mice bearing subcutaneous tumor xenografts were orally treated with 10, 30, 70, or 100 mg/kg bay-598 once daily for 3 days. results showed that bay-598 could significantly reduce the methylation with doses starting from 30 mg/kg, with most significant effects in the 100 mg/kg group. treatment with 10 mg/kg bay-598 showed no significant effect on the methylation level, although the exposure at 10 mg/kg was close to the cellular ic50 for about 9 h, indicating an even higher exposure as the ic50 to achieve in-vivo effects [1].

IC 50

27 nm

References

[1] eggert e,hillig rc,koehr s,et al. discovery and characterization of a highly potent and selective aminopyrazoline-based in vivo probe (bay-598) for the protein lysine methyltransferase smyd2. j med chem.2016 may 26;59(10):4578-600.

Hexanoic acid, 3-[[(1,1-dimethylethoxy)carbonyl]amino]-2-hydroxy-5-methyl-, (3aS,4R,7R,8aS,9S,10aR,12aS,12bR,13S,13aS)-7,12a-bis(acetyloxy)-13-(benzoyloxy)-3a,4,7,8,8a,9,10,10a,12,12a,12b,13-dodecahyd ro-9-hydroxy-5,8a,14,14-tetramethyl-2,8-dioxo-6,13a-methano-13aH-oxeto[2'',3'':5',6']benzo[1',2':4,5]cyclodeca[1,2-d]-1,3-dioxol-4-yl ester, (2R,3S)-(186348-23-2)Related Product Information

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