WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 404910
Description: UNC0638 is an inhibitor of G9a and GLP with excellent potency and selectivity over a wide range of epigenetic and non-epigenetic targets. UNC0638 treatment of a variety of cell lines resulted in lower global H3K9me2 levels, equivalent to levels observed for small hairpin RNA knockdown of G9a and GLP with the functional potency of UNC0638 being well separated from its toxicity. UNC0638 markedly reduced the clonogenicity of MCF7 cells, reduced the abundance of H3K9me2 marks at promoters of known G9a-regulated endogenous genes and disproportionately affected several genomic loci encoding microRNAs.
MedKoo Cat#: 404910
Chemical Formula: C30H47N5O2
Exact Mass: 509.37
Molecular Weight: 509.72648
Elemental Analysis: C, 70.69; H, 9.29; N, 13.74; O, 6.28
Synonym: UNC0638, UNC-0638, UNC 0638
IUPAC/Chemical Name: 2-cyclohexyl-N-(1-isopropylpiperidin-4-yl)-6-methoxy-7-(3-(pyrrolidin-1-yl)propoxy)quinazolin-4-amine
InChi Key: QOECJCJVIMVJGX-UHFFFAOYSA-N
InChi Code: InChI=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)
SMILES Code: COC1=CC2=C(NC3CCN(C(C)C)CC3)N=C(C4CCCCC4)N=C2C=C1OCCCN5CCCC5
Appearance: White solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
The following data is based on the product molecular weight 509.72648 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
|Concentration / Solvent Volume / Mass||1 mg||5 mg||10 mg|
|1 mM||1.15 mL||5.76 mL||11.51 mL|
|5 mM||0.23 mL||1.15 mL||2.3 mL|
|10 mM||0.12 mL||0.58 mL||1.15 mL|
|50 mM||0.02 mL||0.12 mL||0.23 mL|
1: Machleidt T, Robers MB, Hermanson SB, Dudek JM, Bi K. TR-FRET cellular assays for interrogating posttranslational modifications of histone H3. J Biomol Screen. 2011 Dec;16(10):1236-46. Epub 2011 Oct 4. PubMed PMID: 21972037.
2: Hauser AT, Jung M. Chemical probes: sharpen your epigenetic tools. Nat Chem Biol. 2011 Jul 18;7(8):499-500. doi: 10.1038/nchembio.615. PubMed PMID: 21769094.
3: Vedadi M, Barsyte-Lovejoy D, Liu F, Rival-Gervier S, Allali-Hassani A, Labrie V, Wigle TJ, Dimaggio PA, Wasney GA, Siarheyeva A, Dong A, Tempel W, Wang SC, Chen X, Chau I, Mangano TJ, Huang XP, Simpson CD, Pattenden SG, Norris JL, Kireev DB, Tripathy A, Edwards A, Roth BL, Janzen WP, Garcia BA, Petronis A, Ellis J, Brown PJ, Frye SV, Arrowsmith CH, Jin J. A chemical probe selectively inhibits G9a and GLP methyltransferase activity in cells. Nat Chem Biol. 2011 Jul 10;7(8):566-74. doi: 10.1038/nchembio.599. Erratum in: Nat Chem Biol. 2011 Sep;7(9):648. Nat Chem Biol. 2011;7(8):following 574. PubMed PMID: 21743462; PubMed Central PMCID: PMC3184254.
UNC0638 was a potent G9a (IC50 < 15 nM (n = 4)) and GLP inhibitor (IC50 = 19 Â± 1 nM (n = 2)) in these SAHH-coupled assays (Table 1). An endoproteinase-coupled microfluidic capillary electrophoresis (MCE) assay, which is orthogonal and complementary to the SAHH-coupled assay, was also used to evaluate G9a inhibition by UNC0638, yielding an IC50 < 10 nM (n = 3). In addition, UNC0638 displaced a fluorescein-labeled 15-mer H3 peptide (residues 1Â–15) with high efficiency in a G9a fluorescence-polarization assay, suggesting that UNC0638 binds in the substrate peptidebinding site of G9a. UNC0638 also stabilized G9a and GLP in differential scanning fluorimetry (DSF) experiments, with Tm shifts of 4 Â°C and 8 Â°C, respectively, consistent with high-affinity binding.