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| 25mg |
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Purity: ≥98%
A-196 (A196) is a potent, selective and first-in-class inhibitor of SUV420H1 and SUV420H2 (IC50= 25 and 144 nM) with anticancer activity. It inhibits the di- and trimethylation of H4K20me in multiple cell lines. The in vitro activity of A-196 includes inhibition of SUV420H1 with IC50 of 25 nM and SUV420H2 with IC50 of 144 nM for methylation of H4K20me and greater than 100-fold selectivity over other histone methyltransferases and non-epigenetic targets. A-196 is a substrate-competitive inhibitor of both SUV4-20 enzymes. In cells, A-196 induced a global decrease in H4K20me2 and H4K20me3 and a concomitant increase in H4K20me1. A-196 inhibited 53BP1 foci formation upon ionizing radiation and reduced NHEJ-mediated DNA-break repair but did not affect homology-directed repair. These results demonstrate the role of SUV4-20 enzymatic activity in H4K20 methylation and DNA repair. A-196 represents a first-in-class chemical probe of SUV4-20 to investigate the role of histone methyltransferases in genomic integrity.
| ln Vitro |
After 48 hours of treatment with A-196 (0-5 μM; U2OS cells), H4K20me1 (EC50 value of 735 nM) increases, but H4K20me2 and H4K20me3 (EC50 values of 262 and 370 nM, respectively) decrease (see reference 1). In cells from various tissue types, A-196 (10 μM; 72 hours; wild-type, Suv4-20h double knockout, and inhibitor-treated mouse embryonic fibroblasts) inhibits the SUV4-20 enzyme without showing any signs of toxicity [1].
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| ln Vivo |
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| Cell Assay |
Western Blot Analysis[1]
Cell Types: U2OS cells Tested Concentrations: 0 μM, 0.075 μM, 0.15 μM, 0.3 μM, 0.6 μM, 1.25 μM, 2.5 μM, 5 μM Incubation Duration: 48 hrs (hours) Experimental Results: Increased in H4K20me1 and diminished in both H4K20me2 and H4K20me3. |
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| References |
| Molecular Formula |
C18H16CL2N4
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| Molecular Weight |
359.25244140625
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| Exact Mass |
358.075
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| CAS # |
1982372-88-2
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| Related CAS # |
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| PubChem CID |
117072548
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| Appearance |
Light brown to brown solid powder
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| LogP |
4.5
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
24
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| Complexity |
412
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| Defined Atom Stereocenter Count |
0
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| SMILES |
ClC1C(=CC2=C(C3C=CN=CC=3)N=NC(=C2C=1)NC1CCCC1)Cl
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| InChi Key |
ABGOSOMRWSYAOB-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C18H16Cl2N4/c19-15-9-13-14(10-16(15)20)18(22-12-3-1-2-4-12)24-23-17(13)11-5-7-21-8-6-11/h5-10,12H,1-4H2,(H,22,24)
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| Chemical Name |
6,7-dichloro-N-cyclopentyl-4-pyridin-4-ylphthalazin-1-amine
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1 mg/mL (2.78 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 10.0 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 1 mg/mL (2.78 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 10.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 1 mg/mL (2.78 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.7836 mL | 13.9179 mL | 27.8358 mL | |
| 5 mM | 0.5567 mL | 2.7836 mL | 5.5672 mL | |
| 10 mM | 0.2784 mL | 1.3918 mL | 2.7836 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
A-196 is potent peptide-site competitive inhibitor of SUV420H1 and SUV420H2.Nat Chem Biol.2017 Mar;13(3):317-324. |
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A-196 directly binds to SUV420H1.
A-196 inhibits 53BP1 foci formation and NHEJ proficiency.Nat Chem Biol.2017 Mar;13(3):317-324. |
Crystal structure of A-196 bound to SUV420H1.Nat Chem Biol.2017 Mar;13(3):317-324. |
A-196 inhibits H4K20 di- and trimethylation in cells.Nat Chem Biol.2017 Mar;13(3):317-324. |
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