AZ505
Based on 22 publication(s) in Google Scholar
AZ505 is a potent and selective SMYD2 inhibitor with an IC50 of 0.12 μM.
For research use only. We do not sell to patients.
- Purity: 99.98%
- CAS No.: 1035227-43-0
- Formula: C29H38Cl2N4O4
- Molecular Weight:577.54
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Storage:Powder -20°C, 3 years ; In solvent -80°C, 6 months , -20°C, 1 month
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
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Solvent & Solubility
- Protocol
- Purity & Documentation
- References
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Help & FAQs
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Epigenetics Compound Library
HY-L005
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HY-L158
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HY-L005M
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Methylation Compound Library
HY-L203
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HY-L205
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Posttranslational Modification Library
HY-L226
Publications Citing Use of MedChemExpress (MCE) AZ505
More- Cell. 2023 Apr 27;186(9):1968-1984.e20. [Abstract]
- J Clin Invest. 2017 Jun 30;127(7):2751-2764. [Abstract]
- Theranostics. 2019 Oct 22;9(26):8377-8391. [Abstract]
- Sci Adv. 2023 Jun 16;9(24):eade6624. [Abstract]
- Sci Adv. 2020 Oct 30;6(44):eabb3154. [Abstract]
- Cell Death Dis. 2022 Jan 12;13(1):52. [Abstract]
- Cell Death Dis. 2021 May 2;12(5):439. [Abstract]
- Cell Death Dis. 2018 Feb 27;9(3):326. [Abstract]
- Oncogene. 2021 Apr;40(15):2711-2724. [Abstract]
- Cell Death Discov. 2022 Jun 6;8(1):274. [Abstract]
- Biochem Pharmacol. 2026 Jan;243(Pt 2):117562. [Abstract]
- Cells. 2022 Apr 8;11(8):1262. [Abstract]
- FASEB J. 2021 Jul;35(7):e21715. [Abstract]
- Biomedicines. 2024 Oct 8;12(10):2279. [Abstract]
- Development. 2020 Sep 28;147(18):dev190678. [Abstract]
- Exp Cell Res. 2021 Jul 15;404(2):112649. [Abstract]
- Am J Physiol Renal Physiol. 2022 Aug 1;323(2):F227-F242. [Abstract]
- Mol Carcinog. 2023 Aug;62(8):1119-1135. [Abstract]
- Mol Carcinog. 2023 Jul;62(7):940-950. [Abstract]
- Clin Exp Pharmacol Physiol. 2025 Jul;52(7):e70035. [Abstract]
- J Bone Metab. 2021 Nov;28(4):297-305. [Abstract]
- Research Square Preprint. 2021 Oct.
Customer Validation & Images
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All Histone Methyltransferase Isoforms
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Biological Activity
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SMYD2 |
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| MDA-MB-231 | IC50 |
2900 nM
Compound: 1; AZ505
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Inhibition of N-terminal 2xc-myc-tagged human SMYD2 transfected in human MDA-MB-231 cells assessed as reduction in AHNAK methylation after 72 hrs by ICW assay
Inhibition of N-terminal 2xc-myc-tagged human SMYD2 transfected in human MDA-MB-231 cells assessed as reduction in AHNAK methylation after 72 hrs by ICW assay
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[PMID: 27075367] |
| MDA-MB-231 | IC50 |
13.1 μM
Compound: AZ505
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Antiproliferative activity against human MDA-MB-231 cells assessed as inhibition of cell growth incubated for 72 hrs by CellTiter-Glo luminescent cell viability assay
Antiproliferative activity against human MDA-MB-231 cells assessed as inhibition of cell growth incubated for 72 hrs by CellTiter-Glo luminescent cell viability assay
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[PMID: 34656041] |
| U2OS | IC50 |
<10000 nM
Compound: 1; AZ505
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Inhibition of SMYD2 (unknown origin) expressed in human U2OS cells assessed as reduction in p53 methylation by Western blot analysis
Inhibition of SMYD2 (unknown origin) expressed in human U2OS cells assessed as reduction in p53 methylation by Western blot analysis
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[PMID: 27075367] |
AZ505 is highly selective and shows an activity at submicromolar concentrations in vitro. The IC50 of AZ505 for SMYD2 is 0.12 μM, which is >600-fold greater than the IC50s of AZ505 for other histone methyltransferases, such as SMYD3 (IC50>83.3 μM), DOT1L (IC50>83.3 μM) and EZH2 (IC50>83.3 μM)[1]. AZ505 is a potent and selective SMYD2 inhibitor with an IC50 of 0.12 μM. The human SMYD (SET and MYND domain-containing protein) family of protein lysine methyltransferases contains five members (SMYD1-5). Moreover, AZ505 fails to inhibit the enzymatic activities of a panel of protein lysine methyltransferases. AZ505 is nominated for ITC binding study with Kd of 0.5 μM. In contrast, the calculated Kd for the p53 substrate peptide is 3.7 μM. AZ505 binding to SMYD2 is driven primarily by entropy, which often suggests that binding is mediated by hydrophobic interactions with few specific hydrogen bonds[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Chemical Information
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CAS No. 1035227-43-0
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Appearance Solid
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Molecular Weight 577.54
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Formula C29H38Cl2N4O4
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Color Off-white to light brown
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SMILES
O=C(N(C1CCCCC1)CCNCCC2=C(OCC(N3)=O)C3=C(O)C=C2)CCNCCC4=CC=C(Cl)C(Cl)=C4
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Powder -20°C 3 years In solvent -80°C 6 months -20°C 1 month
Publications (22)
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Journal Impact Factor
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Most Recent
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Cell
Positive selection of somatically mutated clones identifies adaptive pathways in metabolic liver disease. [Abstract]2023 Apr 27;186(9):1968-1984.e20. PMID: 37040760 -
J Clin Invest
Lysine methyltransferase SMYD2 promotes cyst growth in autosomal dominant polycystic kidney disease. [Abstract]2017 Jun 30;127(7):2751-2764. PMID: 28604386
AZ505 purchased from MedChemExpress. Usage Cited in: J Clin Invest. 2017 Jun 30;127(7):2751-2764. [Abstract]
PKD-associated signaling pathways can be affected by SMYD2 in Pkd1 mutant renal epithelial cells and cystic tissues. Western blot analysis of the phosphorylation of ERK, S6, AKT, and Rb as well as the total protein levels of these proteins in Pkd1-null MEK cells with or without AZ505 treatment for 2 hours.
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Theranostics
Inhibition of SMYD2 suppresses tumor progression by down-regulating microRNA-125b and attenuates multi-drug resistance in renal cell carcinoma. [Abstract]2019 Oct 22;9(26):8377-8391. PMID: 31754403 -
Sci Adv
SMYD2 inhibition-mediated hypomethylation of Ku70 contributes to impaired nonhomologous end joining repair and antitumor immunity. [Abstract]2023 Jun 16;9(24):eade6624. PMID: 37315132 -
Sci Adv
Cross-talk between CDK4/6 and SMYD2 regulates gene transcription, tubulin methylation, and ciliogenesis. [Abstract]2020 Oct 30;6(44):eabb3154. PMID: 33127671 -
Cell Death Dis
SMYD2 targets RIPK1 and restricts TNF-induced apoptosis and necroptosis to support colon tumor growth. [Abstract]2022 Jan 12;13(1):52. PMID: 35022391 -
Cell Death Dis
2021 May 2;12(5):439. PMID: 33935284 -
Cell Death Dis
2018 Feb 27;9(3):326. PMID: 29487338
AZ505 purchased from MedChemExpress. Usage Cited in: Cell Death Dis. 2018 Feb 27;9(3):326. [Abstract]
Inhibition of SMYD2 with AZ505 (40 μM, 2 h) decreases the methylation and phosphorylation of STAT3 and p65, but dpes not affect their expression in MDA-MB231 cells.
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Oncogene
2021 Apr;40(15):2711-2724. PMID: 33712705 -
Cell Death Discov
SMYD2 aggravates gastrointestinal stromal tumor via upregulation of EZH2 and downregulation of TET1. [Abstract]2022 Jun 6;8(1):274. PMID: 35668081 -
Biochem Pharmacol
Lysine methylation-mediated SMYD2 degradation by casticin sensitizes non-small-cell lung cancer cells to osimertinib therapy. [Abstract]2026 Jan;243(Pt 2):117562. PMID: 41314435 -
Cells
SMYD2 Inhibition Downregulates TMPRSS2 and Decreases SARS-CoV-2 Infection in Human Intestinal and Airway Epithelial Cells. [Abstract]2022 Apr 8;11(8):1262. PMID: 35455942 -
FASEB J
Critical roles of SMYD2 lysine methyltransferase in mediating renal fibroblast activation and kidney fibrosis. [Abstract]2021 Jul;35(7):e21715. PMID: 34143514 -
Biomedicines
SMYD2 Promotes Calcium Oxalate-Induced Glycolysis in Renal Tubular Epithelial Cells via PTEN Methylation. [Abstract]2024 Oct 8;12(10):2279. PMID: 39457592 -
Development
The Gridlock transcriptional repressor impedes vertebrate heart regeneration by restricting expression of lysine methyltransferase. [Abstract]2020 Sep 28;147(18):dev190678. PMID: 32988975 -
Exp Cell Res
2021 Jul 15;404(2):112649. PMID: 34015314 -
Am J Physiol Renal Physiol
Cross talk between lysine methyltransferase Smyd2 and TGF-β-Smad3 signaling promotes renal fibrosis in autosomal dominant polycystic kidney disease. [Abstract]2022 Aug 1;323(2):F227-F242. PMID: 35759739 -
Mol Carcinog
PRMT1 inhibition promotes ferroptosis sensitivity via ACSL1 upregulation in acute myeloid leukemia. [Abstract]2023 Aug;62(8):1119-1135. PMID: 37144835 -
Mol Carcinog
2023 Jul;62(7):940-950. PMID: 37036190
AZ505 purchased from MedChemExpress. Usage Cited in: Mol Carcinog. 2023 Jul;62(7):940-950. [Abstract]
AZ505 ditrifluoroacetate (AZ505; 20 μM; 48 h) decreases the expression of c-Myc in PC3 and DU145 cells.
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Clin Exp Pharmacol Physiol
A Novel Inhibitor of Methyltransferase SMYD2, AZ505 Protects Against Peritoneal Fibrosis in Mice. [Abstract]2025 Jul;52(7):e70035. PMID: 40414794 -
J Bone Metab
2021 Nov;28(4):297-305. PMID: 34905676 -
Solvent & Solubility
DMSO : ≥ 135 mg/mL (233.75 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
* "≥" means soluble, but saturation unknown.
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: 6.25 mg/mL (10.82 mM); Clear solution; Need ultrasonic
This protocol yields a clear solution of 6.25 mg/mL.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (62.5 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: 6.25 mg/mL (10.82 mM); Clear solution; Need ultrasonic
This protocol yields a clear solution of 6.25 mg/mL.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (62.5 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:
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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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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%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.
Protocol
SMYD2 is expressed in insect cells and purified. AlphaScreen technology is used to screen our chemical library for small molecule inhibitors of SMYD2. Methylation (12 μL) reactions are carried out in TDT buffer (50 mM Tris-HCl [pH 9.0], 2 mM DTT, and 0.01% Tween 20) at room temperature using 1.25 nM SMYD2 protein, 200 nM SAM, and 100 nM biotinylated p53 peptide substrate (Biotin-aminohexanoyl-GSRAHSSHLKSKKGQSTSRH) in low volume 384-well plates. Following a 75 min incubation period, reactions are quenched by the addition of 5 μL of detection solution (20 mM HEPES [pH 7.4], 1.7 mg/mL BSA, 340 mM NaCl, 680 μM SAH, 0.04 mg/mL Streptavidin-coated AlphaScreen donor, and Protein A-coated acceptor beads), and 1 nM of a custom p53K370me1 polyclonal antibody. Reaction plates are incubated overnight in the dark at room temperature, and read using an Envision 2101 Multi-label Reader. Compounds showing >50% inhibition of SMYD2 are nominated for concentration dose-response determination, and are also subjected to an artifact assay. Seven compound concentrations are selected beginning at 30 μM with six half-log dilution steps. The artifact assay conditions are identical to those in the SMYD2 enzymatic activity assay, except for the absence of SMYD2 protein and the presence of 1 nM methylated p53 peptide. IC50 values are calculated from dose-response data using in-house software[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Purity & Documentation
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Data Sheet (273 KB)
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SDS (394 KB)
- English - EN (394 KB)
- Français - FR (394 KB)
- Deutsch - DE (394 KB)
- Norwegian - NO (394 KB)
- Español - ES (394 KB)
- Swedish - SV (394 KB)
- Italian - IT (394 KB)
- Korean - KR (394 KB)
- Portuguese - PT (394 KB)
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Handling Instructions (2659 KB)
References
[1]. Komatsu S, et al. Overexpression of SMYD2 contributes to malignant outcome in gastric cancer. Br J Cancer. 2015 Jan 20;112(2):357-64. [Content Brief]
[2]. Ferguson AD, et al. Structural basis of substrate methylation and inhibition of SMYD2. Structure. 2011 Sep 7;19(9):1262-73. [Content Brief]
[3]. Li LX, et al. Lysine methyltransferase SMYD2 promotes cyst growth in autosomal dominant polycystic kidney disease. J Clin Invest. 2017 Jun 30;127(7):2751-2764. [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 | 1.7315 mL | 8.6574 mL | 17.3148 mL | 43.2870 mL |
| 5 mM | 0.3463 mL | 1.7315 mL | 3.4630 mL | 8.6574 mL | |
| 10 mM | 0.1731 mL | 0.8657 mL | 1.7315 mL | 4.3287 mL | |
| 15 mM | 0.1154 mL | 0.5772 mL | 1.1543 mL | 2.8858 mL | |
| 20 mM | 0.0866 mL | 0.4329 mL | 0.8657 mL | 2.1644 mL | |
| 25 mM | 0.0693 mL | 0.3463 mL | 0.6926 mL | 1.7315 mL | |
| 30 mM | 0.0577 mL | 0.2886 mL | 0.5772 mL | 1.4429 mL | |
| 40 mM | 0.0433 mL | 0.2164 mL | 0.4329 mL | 1.0822 mL | |
| 50 mM | 0.0346 mL | 0.1731 mL | 0.3463 mL | 0.8657 mL | |
| 60 mM | 0.0289 mL | 0.1443 mL | 0.2886 mL | 0.7215 mL | |
| 80 mM | 0.0216 mL | 0.1082 mL | 0.2164 mL | 0.5411 mL | |
| 100 mM | 0.0173 mL | 0.0866 mL | 0.1731 mL | 0.4329 mL |
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