UNC0638 - CAS 1255580-76-7

UNC0638 is an inhibitor of protein lysine methyltransferases G9a(IC50<15 nM) and GLP(IC50=19 nM) with excellent potency and selectivity over a wide range of epigenetic and non-epigenetic targets.
IC50 value: <15 nM (G9a); 19±1 nM (GLP) [1]
Target: Protein lysine methyltransferases G9a/GLP
in vitro: UNC0638 was a potent G9a (IC50 < 15 nM (n = 4)) and GLP inhibitor (IC50 = 19 ± 1 nM (n = 2)) in these SAHH-coupled assays. UNC0638 also stabilized G9a and GLP in differential scanning fluorimetry (DSF) experiments, with Tm shifts of 4 °C and 8 °C, respectively, consistent with high-affinity binding [1]. Of note, UNC0638 had weak but measurable activity against JMJD2E (IC50 = 4,500 ± 1,100 nM (n = 3)), a Jumonji protein demethylase and DNA methyltransferase DNMT1 (IC50 = 107,000 ± 6,000 nM (n = 2)). Nevertheless, the selectivity of UNC0638 for G9a and GLP over JMJD2E was >200-fold, and selectivity for G9a and GLP over DNMT1 was >5,000-fold [1]. In MDA-MB-231 cells, UNC0638 (48 h exposure) reduced H3K9me2 levels in a concentration-dependent manner with an IC50 of 81 ± 9 nM (n = 3), which indicates considerably higher potency than BIX01294 (IC50 = 500 ± 43 nM (n = 3)) [1]. UNC0638 could efficiently reduce H3K9me2 levels of cultured sheep foetal fibroblast cells in a concentration-dependent manner. Cloned embryos were subsequently produced from UNC0638-treated donor cells with down-regulated H3K9me2, but their in vitro development was not improved when compared with the control [2].
in vivo:

Catalog Number: I001019

CAS Number: 1255580-76-7

PubChem Substance ID:355039351

Molecular Formula: C₃₀H₄₇N₅O₂

Molecular Weight:509.72

Purity: ≥95%

* For research use only. Not for human or veterinary use.

Synonym

Synonyms2-cyclohexyl-6-methoxy-N-(1-propan-2-ylpiperidin-4-yl)-7-(3-pyrrolidin-1-ylpropoxy)quinazolin-4-amine

Property

Molecular Formula: C₃₀H₄₇N₅O₂
Molecular Weight509.72
Target:Histone Methyltransferase
SolubilityDMSO: ≥ 34 mg/mL
Purity≥95%
StorageStore at -20°C
MDLMFCD17215972
IC50<15 nM (G9a); 19±1 nM (GLP) [1]

Computed Descriptor

InChIInChI=1S/C30H47N5O2/c1-22(2)35-17-12-24(13-18-35)31-30-25-20-27(36-3)28(37-19-9-16-34-14-7-8-15-34)21-26(25)32-29(33-30)23-10-5-4-6-11-23/h20-24H,4-19H2,1-3H3,(H,31,32,33)
InChIKeyQOECJCJVIMVJGX-UHFFFAOYSA-N
SMILESCC(C)N1CCC(CC1)NC2=NC(=NC3=CC(=C(C=C32)OC)OCCCN4CCCC4)C5CCCCC5