WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H404910
CAS#: 1255580-76-7
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.
Hodoodo Cat#: H404910
Name: UNC-0638
CAS#: 1255580-76-7
Chemical Formula: C30H47N5O2
Exact Mass: 509.37
Molecular Weight: 509.726
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
More Info: UNC0638 was a potent G9a (IC50 < 15 nM (n = 4)) and GLP inhibitor (IC50 = 19 ± 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 1–15) 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 °C and 8 °C, respectively, consistent with high-affinity binding.
| Biological target: | UNC0638 inhibits G9a and GLP histone methyltransferase activity with IC50s of 15 nM and 19 nM, respectively. |
| In vitro activity: | The inhibitory effect of UNC0638 on migration of MDA-MB-231 and BT-549 cells was evaluated by wound-healing assay. After a single layer of cells was scratched to generate the wounds, the two TNBC (triple negative breast cancer) cell lines were treated with 0.5 and 1 µM UNC0638 for 24 h. As demonstrated in Fig. 2E and F, UNC0638 treatment significantly decreased the ability of TNBC cells to migrate and recover the wounded area. The quantitative data presented in Fig. 2H indicated that TNBC inhibited the migration of TNBC cells in a dose-dependent manner. These results indicate that UNC0638 is effective in preventing TNBC cell migration and invasion. Reference: Mol Med Rep. 2018 Feb;17(2):2239-2244. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5783465/ |
| In vivo activity: | The in vivo anti-tumor effect of the G9a inhibitor UNC0638 was tested in mouse xenograft models. H1299 cancer cells were used to establish subcutaneous xenograft tumors in NSG (NOD/SCID/IL2Rgamma null) mice. Compared to the solvent control, treatment with UNC0638 via mini-osmotic pump at the dose of 10 mg/kg significantly suppressed xenograft tumor growth (P = 0.05; Fig. 6a). The average tumor size in the mice treated with UNC0638 on day 28 after the implantation was significantly lower than the tumor weight in the mice treated with PBS (Fig. 6b-c). These results revealed that UNC0638 significantly inhibited tumor growth in a NSG xenograft model. Reference: Mol Cancer. 2018 Oct 22;17(1):153. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6198520/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 50.2 | 98.56 | |
| Ethanol | 75.5 | 148.10 | |
| Water | 6.0 | 11.77 |
The following data is based on the product molecular weight 509.73 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 |
| Formulation protocol: | 1. Nualkaew T, Khamphikham P, Pongpaksupasin P, Kaewsakulthong W, Songdej D, Paiboonsukwong K, Sripichai O, Engel JD, Hongeng S, Fucharoen S, Jearawiriyapaisarn N. UNC0638 induces high levels of fetal hemoglobin expression in β-thalassemia/HbE erythroid progenitor cells. Ann Hematol. 2020 Sep;99(9):2027-2036. doi: 10.1007/s00277-020-04136-w. Epub 2020 Jun 21. PMID: 32567028. 2. Liu XR, Zhou LH, Hu JX, Liu LM, Wan HP, Zhang XQ. UNC0638, a G9a inhibitor, suppresses epithelial‑mesenchymal transition‑mediated cellular migration and invasion in triple negative breast cancer. Mol Med Rep. 2018 Feb;17(2):2239-2244. doi: 10.3892/mmr.2017.8190. Epub 2017 Nov 29. PMID: 29207160; PMCID: PMC5783465. 2. Zhang K, Wang J, Yang L, Yuan YC, Tong TR, Wu J, Yun X, Bonner M, Pangeni R, Liu Z, Yuchi T, Kim JY, Raz DJ. Targeting histone methyltransferase G9a inhibits growth and Wnt signaling pathway by epigenetically regulating HP1α and APC2 gene expression in non-small cell lung cancer. Mol Cancer. 2018 Oct 22;17(1):153. doi: 10.1186/s12943-018-0896-8. PMID: 30348169; PMCID: PMC6198520. |
| In vitro protocol: | 1. Nualkaew T, Khamphikham P, Pongpaksupasin P, Kaewsakulthong W, Songdej D, Paiboonsukwong K, Sripichai O, Engel JD, Hongeng S, Fucharoen S, Jearawiriyapaisarn N. UNC0638 induces high levels of fetal hemoglobin expression in β-thalassemia/HbE erythroid progenitor cells. Ann Hematol. 2020 Sep;99(9):2027-2036. doi: 10.1007/s00277-020-04136-w. Epub 2020 Jun 21. PMID: 32567028. 2. Liu XR, Zhou LH, Hu JX, Liu LM, Wan HP, Zhang XQ. UNC0638, a G9a inhibitor, suppresses epithelial‑mesenchymal transition‑mediated cellular migration and invasion in triple negative breast cancer. Mol Med Rep. 2018 Feb;17(2):2239-2244. doi: 10.3892/mmr.2017.8190. Epub 2017 Nov 29. PMID: 29207160; PMCID: PMC5783465. |
| In vivo protocol: | 1. Zhang K, Wang J, Yang L, Yuan YC, Tong TR, Wu J, Yun X, Bonner M, Pangeni R, Liu Z, Yuchi T, Kim JY, Raz DJ. Targeting histone methyltransferase G9a inhibits growth and Wnt signaling pathway by epigenetically regulating HP1α and APC2 gene expression in non-small cell lung cancer. Mol Cancer. 2018 Oct 22;17(1):153. doi: 10.1186/s12943-018-0896-8. PMID: 30348169; PMCID: PMC6198520. |
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.
