1. Epigenetics Autophagy Anti-infection
  2. VSV Histone Methyltransferase Autophagy Influenza Virus
  3. UNC0638

UNC0638 selectively inhibits G9a and GLP histone methyltransferases with IC50 of 15 nM and 19 nM, respectively. UNC0638 inhibits TNBC cell invasion and migration in vitro. UNC0638 is also an inhibitor of EHMT1/2 and induces fetal hemoglobin (HbF) expression in human erythroid progenitor cell culture. In addition, UNC0638 has anti-FMDV (foot-and-mouth disease virus) and anti-VSV (vesicular stomatitis virus) activities, with excellent potency and selectivity against multiple epigenetic and non-epigenetic targets.

For research use only. We do not sell to patients.

UNC0638 Chemical Structure

UNC0638 Chemical Structure

CAS No. : 1255580-76-7

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Customer Review

Based on 10 publication(s) in Google Scholar

Other Forms of UNC0638:

Top Publications Citing Use of Products

    UNC0638 purchased from MedChemExpress. Usage Cited in: Cell Death Dis. 2018 Jan 26;9(2):129.  [Abstract]

    The effects of treatment with the indicated epigenetic inhibitors on cleaved PARP (Clv-PARP) expression in both PC9/ER and HCC827/ER cells. β-actin is used as a loading control.

    UNC0638 purchased from MedChemExpress. Usage Cited in: Mol Med Rep. 2018 Feb;17(2):2239-2244.  [Abstract]

    UNC0638 suppresses triple negative breast cancer cell migration and invasion by regulating EMT associated proteins. Western blots of EMT associated proteins.
    • Biological Activity

    • Protocol

    • Purity & Documentation

    • References

    • Customer Review

    Description

    UNC0638 selectively inhibits G9a and GLP histone methyltransferases with IC50 of 15 nM and 19 nM, respectively. UNC0638 inhibits TNBC cell invasion and migration in vitro. UNC0638 is also an inhibitor of EHMT1/2 and induces fetal hemoglobin (HbF) expression in human erythroid progenitor cell culture. In addition, UNC0638 has anti-FMDV (foot-and-mouth disease virus) and anti-VSV (vesicular stomatitis virus) activities, with excellent potency and selectivity against multiple epigenetic and non-epigenetic targets[1][2][3][4][5].

    IC50 & Target

    EHMT2/G9a/KMT1C

     

    EHMT1/GLP/KMT1D

     

    Cellular Effect
    Cell Line Type Value Description References
    CWR22R IC50
    0.048 μM
    Compound: 5, UNC0638
    Inhibition of G9a in human 22Rv1 cells assessed as reduction of H3K9me2 after 48 hrs by In-Cell Western assay
    Inhibition of G9a in human 22Rv1 cells assessed as reduction of H3K9me2 after 48 hrs by In-Cell Western assay
    [PMID: 21780790]
    CWR22R EC50
    4.5 μM
    Compound: 5, UNC0638
    Cytotoxicity against human 22Rv1 cells assessed as cell viability after 48 hrs by MTT assay
    Cytotoxicity against human 22Rv1 cells assessed as cell viability after 48 hrs by MTT assay
    [PMID: 21780790]
    HCT-116 IC50
    0.21 μM
    Compound: 5, UNC0638
    Inhibition of G9a in human HCT116 cells assessed as reduction of H3K9me2 after 48 hrs by In-Cell Western assay
    Inhibition of G9a in human HCT116 cells assessed as reduction of H3K9me2 after 48 hrs by In-Cell Western assay
    [PMID: 21780790]
    HCT-116 IC50
    0.24 μM
    Compound: 5, UNC0638
    Inhibition of G9a in p53-deficient human HCT116 cells assessed as reduction of H3K9me2 after 48 hrs by In-Cell Western assay
    Inhibition of G9a in p53-deficient human HCT116 cells assessed as reduction of H3K9me2 after 48 hrs by In-Cell Western assay
    [PMID: 21780790]
    HCT-116 EC50
    11 μM
    Compound: 5, UNC0638
    Cytotoxicity against human HCT116 cells assessed as cell viability after 48 hrs by MTT assay
    Cytotoxicity against human HCT116 cells assessed as cell viability after 48 hrs by MTT assay
    [PMID: 21780790]
    HCT-116 EC50
    11 μM
    Compound: 5, UNC0638
    Cytotoxicity against p53-deficient human HCT116 cells assessed as cell viability after 48 hrs by MTT assay
    Cytotoxicity against p53-deficient human HCT116 cells assessed as cell viability after 48 hrs by MTT assay
    [PMID: 21780790]
    HCT-116 IC50
    3.35 μM
    Compound: UNC0638
    Antiproliferative activity against human HCT116 cells assessed as inhibition of cell viability after 72 hrs by MTT assay
    Antiproliferative activity against human HCT116 cells assessed as inhibition of cell viability after 72 hrs by MTT assay
    [PMID: 27720557]
    HepG2 IC50
    3.7 μM
    Compound: UNC0638
    Antiproliferative activity against human HepG2 cells assessed as inhibition of cell viability after 72 hrs by MTT assay
    Antiproliferative activity against human HepG2 cells assessed as inhibition of cell viability after 72 hrs by MTT assay
    [PMID: 27720557]
    IMR-90 IC50
    0.12 μM
    Compound: 5, UNC0638
    Inhibition of G9a in human IMR90 cells assessed as reduction of H3K9me2 after 48 hrs by In-Cell Western assay
    Inhibition of G9a in human IMR90 cells assessed as reduction of H3K9me2 after 48 hrs by In-Cell Western assay
    [PMID: 21780790]
    IMR-90 EC50
    2.3 μM
    Compound: 5, UNC0638
    Cytotoxicity against human IMR90 cells assessed as cell viability after 48 hrs by MTT assay
    Cytotoxicity against human IMR90 cells assessed as cell viability after 48 hrs by MTT assay
    [PMID: 21780790]
    MCF7 IC50
    0.07 μM
    Compound: 5, UNC0638
    Inhibition of G9a in human MCF7 cells assessed as reduction of H3K9me2 after 48 hrs by In-Cell Western assay
    Inhibition of G9a in human MCF7 cells assessed as reduction of H3K9me2 after 48 hrs by In-Cell Western assay
    [PMID: 21780790]
    MCF7 IC50
    6.99 μM
    Compound: UNC0638
    Antiproliferative activity against human MCF7 cells assessed as inhibition of cell viability after 72 hrs by MTT assay
    Antiproliferative activity against human MCF7 cells assessed as inhibition of cell viability after 72 hrs by MTT assay
    [PMID: 27720557]
    MCF7 IC50
    81 nM
    Compound: 11, UNC0638
    Inhibition of G9a in human MCF7 cells after 48 hrs by clonogenic assay
    Inhibition of G9a in human MCF7 cells after 48 hrs by clonogenic assay
    [PMID: 22975593]
    MDA-MB-231 IC50
    0.081 μM
    Compound: 5, UNC0638
    Inhibition of G9a in human MDA-MB-231 cells assessed as reduction of H3K9me2 after 48 hrs by In-Cell Western assay
    Inhibition of G9a in human MDA-MB-231 cells assessed as reduction of H3K9me2 after 48 hrs by In-Cell Western assay
    [PMID: 21780790]
    MDA-MB-231 EC50
    11 μM
    Compound: 5, UNC0638
    Cytotoxicity against human MDA-MB-231 cells assessed as cell viability after 48 hrs by MTT assay
    Cytotoxicity against human MDA-MB-231 cells assessed as cell viability after 48 hrs by MTT assay
    [PMID: 21780790]
    MDA-MB-231 EC50
    11 μM
    Compound: 126, UNC0638
    Cytotoxicity against human MDA-MB-231 cells by MTT assay
    Cytotoxicity against human MDA-MB-231 cells by MTT assay
    10.1039/C1MD00199J
    MDA-MB-231 EC50
    11000 nM
    Compound: 5, UNC0638
    Cytotoxicity against human MDA-MB-231 cells after 48 hrs by Alamar Blue assay
    Cytotoxicity against human MDA-MB-231 cells after 48 hrs by Alamar Blue assay
    [PMID: 24102134]
    MDA-MB-231 IC50
    3.56 μM
    Compound: 47; UNC0638
    Antiproliferative activity against human MDA-MB-231 cells assessed as inhibition of cell growth measured after 72 hrs by MTT assay
    Antiproliferative activity against human MDA-MB-231 cells assessed as inhibition of cell growth measured after 72 hrs by MTT assay
    [PMID: 35525212]
    MDA-MB-231 IC50
    81 nM
    Compound: 126, UNC0638
    Inhibition of G9a/GLP in human MDA-MB-231 cells assessed as reduction of H3K9me2 level after 48 hrs by flow cytometric analysis
    Inhibition of G9a/GLP in human MDA-MB-231 cells assessed as reduction of H3K9me2 level after 48 hrs by flow cytometric analysis
    10.1039/C1MD00199J
    MDA-MB-231 IC50
    81 nM
    Compound: 11, UNC0638
    Inhibition of G9a in human MDA-MB-231 cells after 48 hrs by clonogenic assay
    Inhibition of G9a in human MDA-MB-231 cells after 48 hrs by clonogenic assay
    [PMID: 22975593]
    MDA-MB-231 IC50
    81 nM
    Compound: 5, UNC0638
    Inhibition of lysine methyltransferase G9a in human MDA-MB-231 cells assessed as reduction of H3K9me2 cellular level by immunofluorescence in-cell Western assay
    Inhibition of lysine methyltransferase G9a in human MDA-MB-231 cells assessed as reduction of H3K9me2 cellular level by immunofluorescence in-cell Western assay
    [PMID: 24102134]
    MOLT-4 GI50
    188 nM
    Compound: 5; UNC0638
    Antiproliferative activity against human MOLT-4 cells assessed as inhibition of cell growth with replenishment of medium with compound on day 4 and 7 and measured after 12 days by ATPlite assay
    Antiproliferative activity against human MOLT-4 cells assessed as inhibition of cell growth with replenishment of medium with compound on day 4 and 7 and measured after 12 days by ATPlite assay
    [PMID: 36882960]
    MOLT-4 GI50
    188 nM
    Compound: 5; UNC0638
    Antiproliferative activity against human MOLT-4 cells assessed as inhibition of cell growth with replenishment of medium with compound on day 4 and 7 by ATPlite assay
    Antiproliferative activity against human MOLT-4 cells assessed as inhibition of cell growth with replenishment of medium with compound on day 4 and 7 by ATPlite assay
    [PMID: 36882960]
    PC-3 IC50
    0.059 μM
    Compound: 5, UNC0638
    Inhibition of G9a in human PC3 cells assessed as reduction of H3K9me2 after 48 hrs by In-Cell Western assay
    Inhibition of G9a in human PC3 cells assessed as reduction of H3K9me2 after 48 hrs by In-Cell Western assay
    [PMID: 21780790]
    PC-3 EC50
    14 μM
    Compound: 5, UNC0638
    Cytotoxicity against human PC3 cells assessed as cell viability after 48 hrs by MTT assay
    Cytotoxicity against human PC3 cells assessed as cell viability after 48 hrs by MTT assay
    [PMID: 21780790]
    RD IC50
    11.17 μM
    Compound: 47; UNC0638
    Antiproliferative activity against human RD cells assessed as inhibition of cell growth incubated for 24 hrs
    Antiproliferative activity against human RD cells assessed as inhibition of cell growth incubated for 24 hrs
    [PMID: 35525212]
    RD IC50
    2.91 μM
    Compound: 47; UNC0638
    Antiproliferative activity against human RD cells assessed as inhibition of cell growth incubated for 144 hrs
    Antiproliferative activity against human RD cells assessed as inhibition of cell growth incubated for 144 hrs
    [PMID: 35525212]
    RD IC50
    3.05 μM
    Compound: 47; UNC0638
    Antiproliferative activity against human RD cells assessed as inhibition of cell growth incubated for 72 hrs
    Antiproliferative activity against human RD cells assessed as inhibition of cell growth incubated for 72 hrs
    [PMID: 35525212]
    Sf9 IC50
    13 nM
    Compound: UNC0638
    Inhibition of N-terminal GST tagged human recombinant EHMT1 (794 to 1294 residues) expressed in baculovirus infected Sf9 insect cells assessed as reduction in conversion of SAH to AMP using histone H3 as substrate and SAH as cosubstrate incubated for 30 m
    Inhibition of N-terminal GST tagged human recombinant EHMT1 (794 to 1294 residues) expressed in baculovirus infected Sf9 insect cells assessed as reduction in conversion of SAH to AMP using histone H3 as substrate and SAH as cosubstrate incubated for 30 m
    [PMID: 31350126]
    Sf9 IC50
    26 nM
    Compound: UNC0638
    Inhibition of N-terminal GST tagged human recombinant EHMT2 (785 to 1210 residues) expressed in baculovirus infected Sf9 insect cells assessed as reduction in conversion of SAH to AMP using histone H3 as substrate and SAH as cosubstrate incubated for 30 m
    Inhibition of N-terminal GST tagged human recombinant EHMT2 (785 to 1210 residues) expressed in baculovirus infected Sf9 insect cells assessed as reduction in conversion of SAH to AMP using histone H3 as substrate and SAH as cosubstrate incubated for 30 m
    [PMID: 31350126]
    SJRH30 IC50
    2.48 μM
    Compound: 47; UNC0638
    Antiproliferative activity against human Rh30 cells assessed as inhibition of cell growth incubated for 144 hrs
    Antiproliferative activity against human Rh30 cells assessed as inhibition of cell growth incubated for 144 hrs
    [PMID: 35525212]
    SJRH30 IC50
    2.64 μM
    Compound: 47; UNC0638
    Antiproliferative activity against human Rh30 cells assessed as inhibition of cell growth incubated for 72 hrs
    Antiproliferative activity against human Rh30 cells assessed as inhibition of cell growth incubated for 72 hrs
    [PMID: 35525212]
    SJRH30 IC50
    5.01 μM
    Compound: 47; UNC0638
    Antiproliferative activity against human Rh30 cells assessed as inhibition of cell growth incubated for 24 hrs
    Antiproliferative activity against human Rh30 cells assessed as inhibition of cell growth incubated for 24 hrs
    [PMID: 35525212]
    THP-1 IC50
    0.24 μM
    Compound: 47; UNC0638
    Antiproliferative activity against human THP-1 cells assessed as inhibition of cell growth incubated for 144 hrs by CellTiter-Glo luminescent cell viability assay
    Antiproliferative activity against human THP-1 cells assessed as inhibition of cell growth incubated for 144 hrs by CellTiter-Glo luminescent cell viability assay
    [PMID: 35525212]
    THP-1 IC50
    0.34 μM
    Compound: 47; UNC0638
    Antiproliferative activity against human THP-1 cells assessed as inhibition of cell growth incubated for 72 hrs by CellTiter-Glo luminescent cell viability assay
    Antiproliferative activity against human THP-1 cells assessed as inhibition of cell growth incubated for 72 hrs by CellTiter-Glo luminescent cell viability assay
    [PMID: 35525212]
    THP-1 IC50
    0.84 μM
    Compound: 47; UNC0638
    Antiproliferative activity against human THP-1 cells assessed as inhibition of cell growth incubated for 24 hrs by CellTiter-Glo luminescent cell viability assay
    Antiproliferative activity against human THP-1 cells assessed as inhibition of cell growth incubated for 24 hrs by CellTiter-Glo luminescent cell viability assay
    [PMID: 35525212]
    In Vitro

    UNC0638, an inhibitor of G9a and GLP with excellent potency and selectivity over a wide range of epigenetic and non-epigenetic targets.The Ki of UNC0638 is determined to be 3.0±0.05 nM (n=2). Consistent with this, the Morrison Ki for UNC0638 is 3.7±0.2 nM (n=3). The selectivity of UNC0638 over a wide range of epigenetic targets is evaluated. Notably, UNC0638 is inactive against other H3K9 (SUV39H1 and SUV39H2), H3K27 (EZH2), H3K4 (SETD7, MLL and SMYD3), H3K79 (DOT1L) and H4K20 (SETD8) methyltransferases, as well as PRDM1, PRDM10 and PRDM12. In addition, UNC0638 is inactive against protein arginine methyltransferases PRMT1 and PRMT3, and HTATIP, a histone acetyltransferase. Of note, UNC0638 has weak but measurable activity against JMJD2E (IC50=4,500±1,100 nM), a Jumonji protein demethylase and DNA methyltransferase DNMT1 (IC50=107,000±6,000 nM). Nevertheless, the selectivity of UNC0638 for G9a and GLP over JMJD2E is >200-fold, and selectivity for G9a and GLP over DNMT1 is >5,000-fold[1]. UNC0638 is a type of small molecule that can specifically inhibit the enzyme activity of histone methyltransferase EHMT and reduce the H3K9 dimethylation (H3K9me2) levels in cells[2].

    MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

    Molecular Weight

    509.73

    Formula

    C30H47N5O2

    CAS No.
    Appearance

    Solid

    Color

    White to yellow

    SMILES

    CC(N1CCC(NC2=C3C=C(OC)C(OCCCN4CCCC4)=CC3=NC(C5CCCCC5)=N2)CC1)C

    Shipping

    Room temperature in continental US; may vary elsewhere.

    Storage
    Powder -20°C 3 years
    4°C 2 years
    In solvent -80°C 2 years
    -20°C 1 year
    Solvent & Solubility
    In Vitro: 

    1M HCl : 100 mg/mL (196.18 mM; ultrasonic and adjust pH to 1 with HCl)

    DMSO : ≥ 30 mg/mL (58.85 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

    *"≥" means soluble, but saturation unknown.

    Preparing
    Stock Solutions
    Concentration Solvent Mass 1 mg 5 mg 10 mg
    1 mM 1.9618 mL 9.8091 mL 19.6182 mL
    5 mM 0.3924 mL 1.9618 mL 3.9236 mL
    View the Complete Stock Solution Preparation Table

    * Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
    Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

    • Molarity Calculator

    • Dilution Calculator

    Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

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    Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

    This equation is commonly abbreviated as: C1V1 = C2V2

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    In Vivo:

    Select the appropriate dissolution method based on your experimental animal and administration route.

    For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
    To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
    The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

    • Protocol 1

      Add each solvent one by one:  10% DMSO    40% PEG300    5% Tween-80    45% Saline

      Solubility: ≥ 2.5 mg/mL (4.90 mM); Clear solution

      This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

      Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.

      Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
    • Protocol 2

      Add each solvent one by one:  10% DMSO    90% (20% SBE-β-CD in Saline)

      Solubility: ≥ 2.5 mg/mL (4.90 mM); Clear solution

      This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

      Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.

      Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
    In Vivo Dissolution Calculator
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    Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
    Please enter your animal formula composition:
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    Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
    The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
    Calculation results:
    Working solution concentration: mg/mL
    Method for preparing stock solution: mg drug dissolved in μL  DMSO (Stock solution concentration: mg/mL).
    The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).
    Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.
     If the continuous dosing period exceeds half a month, please choose this protocol carefully.
    Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
    Purity & Documentation

    Purity: 98.60%

    References

    Complete Stock Solution Preparation Table

    * Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
    Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

    Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
    DMSO / 1M HCl 1 mM 1.9618 mL 9.8091 mL 19.6182 mL 49.0456 mL
    5 mM 0.3924 mL 1.9618 mL 3.9236 mL 9.8091 mL
    10 mM 0.1962 mL 0.9809 mL 1.9618 mL 4.9046 mL
    15 mM 0.1308 mL 0.6539 mL 1.3079 mL 3.2697 mL
    20 mM 0.0981 mL 0.4905 mL 0.9809 mL 2.4523 mL
    25 mM 0.0785 mL 0.3924 mL 0.7847 mL 1.9618 mL
    30 mM 0.0654 mL 0.3270 mL 0.6539 mL 1.6349 mL
    40 mM 0.0490 mL 0.2452 mL 0.4905 mL 1.2261 mL
    50 mM 0.0392 mL 0.1962 mL 0.3924 mL 0.9809 mL
    1M HCl 60 mM 0.0327 mL 0.1635 mL 0.3270 mL 0.8174 mL
    80 mM 0.0245 mL 0.1226 mL 0.2452 mL 0.6131 mL
    100 mM 0.0196 mL 0.0981 mL 0.1962 mL 0.4905 mL
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    • Do most proteins show cross-species activity?

      Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

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