| Size | Price | Stock | Qty |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| 500mg |
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| 1g |
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| Other Sizes |
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PRT4165 (NSC600157) is a potent and selective inhibitor of the PRC1 (polycomb repressive complex 1)-mediated H2A ubiquitylation with potential anticancer activity. It has an IC50 of 3.9 µM for inhibiting PRC1 in a cell-free assay. It inhibits PRC1-mediated H2A ubiquitylation in vivo and in vitro. PRT-4165 also inhibits the accumulation of all detectable ubiquitin at sites of DNA double-strand breaks (DSBs), the retention of several DNA damage response proteins in foci that form around DSBs, and the repair of the DSBs. PRC1-mediated histone ubiquitylation plays an important role in aberrant gene silencing in human cancers and is a potential target for cancer therapy. PRT4165 as a novel chromatin-remodeling compound provides a new tool for the inhibition of ubiquitylation signaling at DNA double-strand breaks.
| Targets |
PRC1
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|---|---|---|---|
| ln Vitro |
PRT4165 is a potent inhibitor of PRC1-mediated H2A ubiquitylation. According to in vitro E3 ubiquitin ligase activity tests, PRT4165 inhibits RING 1A and RNF2 but not RNF8 or RNF168. Either RNF2 or RING1 can contribute to the E3 ubiquitin ligase activity, but PRT4165 can completely inhibit H2A ubiquitylation. When cells are treated with 50 μM PRT4165 for 60 minutes, the amount of total ubiquitylated histone H2A is dramatically reduced.Additionally, it is discovered that unirradiated cells with longer exposure times to PRT4165 (30 and 60 min) have higher levels of γ-H2AX. When compared to mock-treated cells, PRT4165 inhibits double-strand break (DSB) repair at the 8-hour mark. The number of cells in G2/M increases in cells treated with increasing PRT4165 concentrations[1].
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| ln Vivo |
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| Cell Assay |
Cells are treated with different concentrations of the PRT4165 60 min prior to irradiation (2 Gy). Two hours after IR, the cells are harvested. After twice washing the cells in PBS, they are fixed for ten minutes at 37°C using 1% paraformaldehyde. The cells are permeabilized with 90% methanol and kept at -20°C for an entire night after being cooled on ice for one minute. After two PBS washes, fixed cells are blocked for ten minutes using FACS incubation buffer (0.5% BSA in PBS). After that, the cells are stained for one hour at room temperature using an anti-phosphohistone H3 (serine 10) antibody at a 1:500 dilution in FACS incubation buffer[1].
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| Animal Protocol |
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| References |
| Molecular Formula |
C15H9NO2
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|---|---|---|
| Molecular Weight |
235.240
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| Exact Mass |
235.063
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| Elemental Analysis |
C, 76.59; H, 3.86; N, 5.95; O, 13.60
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| CAS # |
31083-55-3
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| Related CAS # |
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| PubChem CID |
207893
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| Appearance |
Yellow solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
452.3±45.0 °C at 760 mmHg
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| Flash Point |
227.0±35.1 °C
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| Vapour Pressure |
0.0±1.1 mmHg at 25°C
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| Index of Refraction |
1.710
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| LogP |
2.7
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
18
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| Complexity |
373
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C1/C(C(C2=C1C=CC=C2)=O)=C/C3=CC=CN=C3
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| InChi Key |
OMHZFEWYVFWVLI-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C15H9NO2/c17-14-11-5-1-2-6-12(11)15(18)13(14)8-10-4-3-7-16-9-10/h1-9H
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| Chemical Name |
2-(3-Pyridinylmethylene)-1H-Indene-1,3(2H)-dione
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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) |
DMSO : 25~11 mg/mL ( 106.27~46.76 mM)
Ethanol : ~4 mg/mL Water : Insoluble |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (10.63 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 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL 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: 2.5 mg/mL (10.63 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 25.0 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: 5%DMSO+Corn oil: 1.2mg/ml |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.2510 mL | 21.2549 mL | 42.5098 mL | |
| 5 mM | 0.8502 mL | 4.2510 mL | 8.5020 mL | |
| 10 mM | 0.4251 mL | 2.1255 mL | 4.2510 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.
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