A-366
Based on 7 publication(s) in Google Scholar
A-366, a chemical probe, is a potent, highly selective, peptide-competitive histone methyltransferase G9a inhibitor with IC50s of 3.3 and 38 nM for G9a and GLP (EHMT1), respectively. A-366 shows >1000-fold selectivity over 21 other methyltransferases. A-366 is also a potent, nanomolar inhibitor of the Spindlin1-H3K4me3-interaction (IC50=182.6 nM). A-366 displays high affinity at human histamine H3 receptor (Ki=17 nM) and shows subtype selectivity among subsets of the histaminergic and dopaminergic receptor families.
For research use only. We do not sell to patients.
- Purity: 98.13%
- CAS No.: 1527503-11-2
- Formula: C19H27N3O2
- Molecular Weight:329.44
-
Storage:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
Publications Citing Use of MedChemExpress (MCE) A-366
More- Cancer Res. 2026 Jun 10. [Abstract]
- Nat Commun. 2026 Feb 12;17(1):1214. [Abstract]
- Theranostics. 2018 Apr 15;8(10):2884-2895. [Abstract]
- Proc Natl Acad Sci U S A. 2019 Feb 19;116(8):2961-2966. [Abstract]
- Diabetes. 2025 Oct 1;74(10):1825-1838. [Abstract]
- iScience. 2024 May 16;27(6):110011. [Abstract]
- Epigenetics Chromatin. 2025 Jan 13;18(1):2. [Abstract]
-
Bio/Physico-chemical Assay
-
Bio/Physico-chemical Assay
-
Bio/Physico-chemical Assay
All Histone Methyltransferase Isoforms
More
Biological Activity
|
EHMT2/G9a/KMT1C |
EHMT1/GLP/KMT1D |
|
Cell Line
|
Type | Value | Description | References |
|---|---|---|---|---|
| Calu-1 | EC50 |
>10 μM
Compound: Chemical probe: A-366
|
Antiproliferative against human Calu-1 cells after 5 days by Cell-Titer Glo assay
Antiproliferative against human Calu-1 cells after 5 days by Cell-Titer Glo assay
|
[PMID: 26147105] |
| Calu-6 | EC50 |
>10 μM
Compound: Chemical probe: A-366
|
Antiproliferative against human Calu-6 cells after 5 days by Cell-Titer Glo assay
Antiproliferative against human Calu-6 cells after 5 days by Cell-Titer Glo assay
|
[PMID: 26147105] |
| CWR22R | EC50 |
>10 μM
Compound: Chemical probe: A-366
|
Antiproliferative against human 22RV1 cells after 5 days by Cell-Titer Glo assay
Antiproliferative against human 22RV1 cells after 5 days by Cell-Titer Glo assay
|
[PMID: 26147105] |
| Daoy | EC50 |
>10 μM
Compound: Chemical probe: A-366
|
Antiproliferative against human Daoy cells after 7 days by Cell-Titer Glo assay
Antiproliferative against human Daoy cells after 7 days by Cell-Titer Glo assay
|
[PMID: 26147105] |
| DU-145 | EC50 |
>10 μM
Compound: Chemical probe: A-366
|
Antiproliferative against human DU-145 cells after 5 days by Cell-Titer Glo assay
Antiproliferative against human DU-145 cells after 5 days by Cell-Titer Glo assay
|
[PMID: 26147105] |
| G-401 | EC50 |
>10 μM
Compound: Chemical probe: A-366
|
Antiproliferative against human G-401 cells after 7 days by Cell-Titer Glo assay
Antiproliferative against human G-401 cells after 7 days by Cell-Titer Glo assay
|
[PMID: 26147105] |
| HL-60 | EC50 |
>10 μM
Compound: Chemical probe: A-366
|
Antiproliferative against human HL-60 cells after 5 days by Cell-Titer Glo assay
Antiproliferative against human HL-60 cells after 5 days by Cell-Titer Glo assay
|
[PMID: 26147105] |
| HT-1080 | EC50 |
>10 μM
Compound: Chemical probe: A-366
|
Antiproliferative against human HT-1080 cells after 5 days by Cell-Titer Glo assay
Antiproliferative against human HT-1080 cells after 5 days by Cell-Titer Glo assay
|
[PMID: 26147105] |
| IMR-32 | EC50 |
>10 μM
Compound: Chemical probe: A-366
|
Antiproliferative against human IMR-32 cells after 7 days by Cell-Titer Glo assay
Antiproliferative against human IMR-32 cells after 7 days by Cell-Titer Glo assay
|
[PMID: 26147105] |
| K562 | EC50 |
>10 μM
Compound: Chemical probe: A-366
|
Antiproliferative against human K562 cells after 5 days by Cell-Titer Glo assay
Antiproliferative against human K562 cells after 5 days by Cell-Titer Glo assay
|
[PMID: 26147105] |
| Kasumi 1 | EC50 |
>10 μM
Compound: Chemical probe: A-366
|
Antiproliferative against human Kasumi-1 cells after 5 days by Cell-Titer Glo assay
Antiproliferative against human Kasumi-1 cells after 5 days by Cell-Titer Glo assay
|
[PMID: 26147105] |
| KMS-11 | EC50 |
>10 μM
Compound: Chemical probe: A-366
|
Antiproliferative against human KMS-11 cells after 5 days by Cell-Titer Glo assay
Antiproliferative against human KMS-11 cells after 5 days by Cell-Titer Glo assay
|
[PMID: 26147105] |
| KMS-12-BM | EC50 |
>10 μM
Compound: Chemical probe: A-366
|
Antiproliferative against human KMS-12-BM cells after 5 days by Cell-Titer Glo assay
Antiproliferative against human KMS-12-BM cells after 5 days by Cell-Titer Glo assay
|
[PMID: 26147105] |
| L-363 | EC50 |
>10 μM
Compound: Chemical probe: A-366
|
Antiproliferative against human L-363 cells after 5 days by Cell-Titer Glo assay
Antiproliferative against human L-363 cells after 5 days by Cell-Titer Glo assay
|
[PMID: 26147105] |
| LN-229 | EC50 |
>10 μM
Compound: Chemical probe: A-366
|
Antiproliferative against human LN-229 cells after 5 days by Cell-Titer Glo assay
Antiproliferative against human LN-229 cells after 5 days by Cell-Titer Glo assay
|
[PMID: 26147105] |
| LNCaP | EC50 |
>10 μM
Compound: Chemical probe: A-366
|
Antiproliferative against human LNCaP cells after 5 days by Cell-Titer Glo assay
Antiproliferative against human LNCaP cells after 5 days by Cell-Titer Glo assay
|
[PMID: 26147105] |
| MOLT-16 | EC50 |
>10 μM
Compound: Chemical probe: A-366
|
Antiproliferative against human MOLT-16 cells after 5 days by Cell-Titer Glo assay
Antiproliferative against human MOLT-16 cells after 5 days by Cell-Titer Glo assay
|
[PMID: 26147105] |
| MV4-11 | EC50 |
>10 μM
Compound: Chemical probe: A-366
|
Antiproliferative against human MV4-11 cells after 5 days by Cell-Titer Glo assay
Antiproliferative against human MV4-11 cells after 5 days by Cell-Titer Glo assay
|
[PMID: 26147105] |
| NCI-H1975 | EC50 |
>10 μM
Compound: Chemical probe: A-366
|
Antiproliferative against human NCI-H1975 cells after 5 days by Cell-Titer Glo assay
Antiproliferative against human NCI-H1975 cells after 5 days by Cell-Titer Glo assay
|
[PMID: 26147105] |
| NCI-H2009 | EC50 |
>10 μM
Compound: Chemical probe: A-366
|
Antiproliferative against human NCI-H2009 cells after 5 days by Cell-Titer Glo assay
Antiproliferative against human NCI-H2009 cells after 5 days by Cell-Titer Glo assay
|
[PMID: 26147105] |
| NCI-H358 | EC50 |
>10 μM
Compound: Chemical probe: A-366
|
Antiproliferative against human NCI-H358 cells after 5 days by Cell-Titer Glo assay
Antiproliferative against human NCI-H358 cells after 5 days by Cell-Titer Glo assay
|
[PMID: 26147105] |
| NCI-H441 | EC50 |
>10 μM
Compound: Chemical probe: A-366
|
Antiproliferative against human NCI-H441 cells after 5 days by Cell-Titer Glo assay
Antiproliferative against human NCI-H441 cells after 5 days by Cell-Titer Glo assay
|
[PMID: 26147105] |
| NCI-H522 | EC50 |
>10 μM
Compound: Chemical probe: A-366
|
Antiproliferative against human NCI-H522 cells after 5 days by Cell-Titer Glo assay
Antiproliferative against human NCI-H522 cells after 5 days by Cell-Titer Glo assay
|
[PMID: 26147105] |
| NCI-H661 | EC50 |
>10 μM
Compound: Chemical probe: A-366
|
Antiproliferative against human NCI-H661 cells after 5 days by Cell-Titer Glo assay
Antiproliferative against human NCI-H661 cells after 5 days by Cell-Titer Glo assay
|
[PMID: 26147105] |
| NCI-H929 | EC50 |
>10 μM
Compound: Chemical probe: A-366
|
Antiproliferative against human NCI-H929 cells after 5 days by Cell-Titer Glo assay
Antiproliferative against human NCI-H929 cells after 5 days by Cell-Titer Glo assay
|
[PMID: 26147105] |
| OPM-2 | EC50 |
>10 μM
Compound: Chemical probe: A-366
|
Antiproliferative against human OPM-2 cells after 5 days by Cell-Titer Glo assay
Antiproliferative against human OPM-2 cells after 5 days by Cell-Titer Glo assay
|
[PMID: 26147105] |
| PA-1 | EC50 |
>10 μM
Compound: Chemical probe: A-366
|
Antiproliferative against human PA-1 cells after 7 days by Cell-Titer Glo assay
Antiproliferative against human PA-1 cells after 7 days by Cell-Titer Glo assay
|
[PMID: 26147105] |
| RPMI-8226 | EC50 |
>10 μM
Compound: Chemical probe: A-366
|
Antiproliferative against human RPMI-8226 cells after 5 days by Cell-Titer Glo assay
Antiproliferative against human RPMI-8226 cells after 5 days by Cell-Titer Glo assay
|
[PMID: 26147105] |
| RS4-11 | EC50 |
>10 μM
Compound: Chemical probe: A-366
|
Antiproliferative against human RS4-11 cells after 5 days by Cell-Titer Glo assay
Antiproliferative against human RS4-11 cells after 5 days by Cell-Titer Glo assay
|
[PMID: 26147105] |
| Sf9 | IC50 |
11 nM
Compound: A-366
|
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 |
13 nM
Compound: A-366
|
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] |
| SK-BR-3 | EC50 |
>10 μM
Compound: Chemical probe: A-366
|
Antiproliferative against human SK-BR-3 cells after 5 days by Cell-Titer Glo assay
Antiproliferative against human SK-BR-3 cells after 5 days by Cell-Titer Glo assay
|
[PMID: 26147105] |
| SK-N-MC | EC50 |
>10 μM
Compound: Chemical probe: A-366
|
Antiproliferative against human SK-N-MC cells after 7 days by Cell-Titer Glo assay
Antiproliferative against human SK-N-MC cells after 7 days by Cell-Titer Glo assay
|
[PMID: 26147105] |
| THP-1 | EC50 |
>10 μM
Compound: Chemical probe: A-366
|
Antiproliferative against human THP-1 cells after 5 days by Cell-Titer Glo assay
Antiproliferative against human THP-1 cells after 5 days by Cell-Titer Glo assay
|
[PMID: 26147105] |
| U2OS | EC50 |
>10 μM
Compound: Chemical probe: A-366
|
Antiproliferative against human U2OS cells after 7 days by Cell-Titer Glo assay
Antiproliferative against human U2OS cells after 7 days by Cell-Titer Glo assay
|
[PMID: 26147105] |
| ZR-75-30 | EC50 |
>10 μM
Compound: Chemical probe: A-366
|
Antiproliferative against human ZR-75-30 cells after 7 days by Cell-Titer Glo assay
Antiproliferative against human ZR-75-30 cells after 7 days by Cell-Titer Glo assay
|
[PMID: 26147105] |
A-366 (0.01-10 μM; 14 days) induces differentiation and affects viability in MV4;11 cells[4].
A-366 (0.3-3 μM; 72 hours) reduces the total levels of H3K9me2 in a time and concentration dependent manner with a cellular EC50 of ~300 nM in PC-3 prostate adenocarcinoma cells. A-366 (0.01-10 μM; 4 days; HL-60 cells) results in a dose-dependent differentiation and a corresponding decrease in proliferation. DNA content analysis of A-366-treated HL-60 cells showed an accumulation of cells in G1 consistent with cytostasis[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
-
Cell Line:MV4;11 cells
-
Concentration:0.01-10 μM
-
Incubation Time:14 days
-
Result:Resulted in inhibited proliferation and a decrease in viability corresponding to the dose response observed for CD11b staining.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
-
Animal Model:6-8 week old SCID-beige female mice (MV4;11 xenografts)[4]
-
Dosage:30 mg/kg
-
Administration:By osmotic mini-pump; daily for 14 days
-
Result:A modest 45% tumor growth inhibition resulting from A-366 treatment in this model.
Chemical Information
-
CAS No. 1527503-11-2
-
Appearance Solid
-
Molecular Weight 329.44
-
Formula C19H27N3O2
-
Color Light yellow to yellow
-
SMILES
COC1=CC2=C(N=C(N)C23CCC3)C=C1OCCCN4CCCC4
-
Shipping
Room temperature in continental US; may vary elsewhere.
-
Storage
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Publications (7)
-
Journal Impact Factor
-
Most Recent
-
Cancer Res
TNG917 is a Potent and Selective Inhibitor of Histone Lysine Methyltransferases EHMT1/2 that Enhances Anti-Tumor Immunity and Immunotherapy Efficacy. [Abstract]2026 Jun 10. PMID: 42268285 -
Nat Commun
Human iPSC-based Modeling of Pulmonary Fibrosis Reveals p300/CBP Inhibition Suppresses Alveolar Transitional Cell State. [Abstract]2026 Feb 12;17(1):1214. PMID: 41680175 -
Theranostics
G9a stimulates CRC growth by inducing p53 Lys373 dimethylation-dependent activation of Plk1. [Abstract]2018 Apr 15;8(10):2884-2895. PMID: 29774081 -
Proc Natl Acad Sci U S A
2019 Feb 19;116(8):2961-2966. PMID: 30718431 -
Diabetes
Molecular Mechanisms of Human Pancreatic Islet Dysfunction Under Overnutrition Metabolic Stress. [Abstract]2025 Oct 1;74(10):1825-1838. PMID: 40773375
A-366 purchased from MedChemExpress. Usage Cited in: Diabetes. 2025 Oct 1;74(10):1825-1838. [Abstract]
Insulin secretion, normalized by total content, of EndoC-βH1 cells treated with A-366 under different conditions.
A-366 purchased from MedChemExpress. Usage Cited in: Diabetes. 2025 Oct 1;74(10):1825-1838. [Abstract]
Principal component (PC) analysis of the RNA-seq data shows the separation of samples along two axes corresponding to glucolipotoxicity (GL) treatment and A-366.
A-366 purchased from MedChemExpress. Usage Cited in: Diabetes. 2025 Oct 1;74(10):1825-1838. [Abstract]
RRHO map comparing the differential expression of GL vs. Ctrl (x-axis) and A-366 vs. on drug (y-axes).
-
iScience
Transcriptional synergy in human aortic endothelial cells is vulnerable to combination p300/CBP and BET bromodomain inhibition. [Abstract]2024 May 16;27(6):110011. PMID: 38868181 -
Epigenetics Chromatin
H3K9 post-translational modifications regulate epiblast/primitive endoderm specification in rabbit blastocysts. [Abstract]2025 Jan 13;18(1):2. PMID: 39800758
Solvent & Solubility
DMSO : 50 mg/mL (151.77 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
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, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
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, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
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.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (7.59 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.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.5 mg/mL (7.59 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.
Please enter the basic information of animal experiments:
-
-
-
-
Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
-
%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
-
%+
-
+%Tween-80 + +
-
%Saline +
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).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
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
-
Data Sheet (277 KB)
-
SDS (393 KB)
- English - EN (393 KB)
- Français - FR (393 KB)
- Deutsch - DE (393 KB)
- Norwegian - NO (393 KB)
- Español - ES (393 KB)
- Swedish - SV (393 KB)
- Italian - IT (393 KB)
- Korean - KR (393 KB)
- Portuguese - PT (393 KB)
-
Handling Instructions (2659 KB)
References
[1]. Reiner D, et al. Epigenetics meets GPCR: inhibition of histone H3 methyltransferase (G9a) and histamine H3 receptor for Prader-Willi Syndrome. Sci Rep. 2020;10(1):13558. Published 2020 Aug 11. [Content Brief]
[2]. Wagner T, et al. Identification of a small-molecule ligand of the epigenetic reader protein Spindlin1 via a versatile screening platform. Nucleic Acids Res. 2016;44(9):e88. [Content Brief]
[3]. Sweis RF, et al. Discovery and development of potent and selective inhibitors of histone methyltransferase g9a. ACS Med Chem Lett. 2014;5(2):205-209. Published 2014 Jan 2. [Content Brief]
[4]. Pappano WN, et al. The Histone Methyltransferase Inhibitor A-366 Uncovers a Role for G9a/GLP in the Epigenetics of Leukemia. PLoS One. 2015;10(7):e0131716. Published 2015 Jul 6. [Content Brief]
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, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 3.0355 mL | 15.1773 mL | 30.3545 mL | 75.8864 mL |
| 5 mM | 0.6071 mL | 3.0355 mL | 6.0709 mL | 15.1773 mL | |
| 10 mM | 0.3035 mL | 1.5177 mL | 3.0355 mL | 7.5886 mL | |
| 15 mM | 0.2024 mL | 1.0118 mL | 2.0236 mL | 5.0591 mL | |
| 20 mM | 0.1518 mL | 0.7589 mL | 1.5177 mL | 3.7943 mL | |
| 25 mM | 0.1214 mL | 0.6071 mL | 1.2142 mL | 3.0355 mL | |
| 30 mM | 0.1012 mL | 0.5059 mL | 1.0118 mL | 2.5295 mL | |
| 40 mM | 0.0759 mL | 0.3794 mL | 0.7589 mL | 1.8972 mL | |
| 50 mM | 0.0607 mL | 0.3035 mL | 0.6071 mL | 1.5177 mL | |
| 60 mM | 0.0506 mL | 0.2530 mL | 0.5059 mL | 1.2648 mL | |
| 80 mM | 0.0379 mL | 0.1897 mL | 0.3794 mL | 0.9486 mL | |
| 100 mM | 0.0304 mL | 0.1518 mL | 0.3035 mL | 0.7589 mL |