| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 1g |
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| Other Sizes |
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| Targets |
p53 protein
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|---|---|
| ln Vitro |
BAY 1892005 Cell growth can be inhibited by the p53 mutant cell lines Huh7 (IC50=11.2 μM) and H358 (IC50=11.1 μM) [1].
BAY 249716 showed significant stabilization of all three p53 protein variants, whereas BAY 1892005 showed stabilization of p53WT and p53Y220C, indicating direct interaction with p53. BAY 1892005 contains a reactive head group (Figure 2A) that could be involved in covalent binding to p53. Indeed, by mass spectrometry, we confirmed that BAY 1892005 binds covalently to mutant p53R175H and p53Y220C (Figures 2B and S2). Taken together we conclude that the identified aminothiazoles potentially directly interact with structural p53 mutant proteins. [1] |
| Enzyme Assay |
Intact mass analysis: 25 µM of p53H175R and p53Y220C protein were incubated with 100 µM BAY 1892005. Compound dilution were done in sodium acetate from a 10 mM stock solution in DMSO resulting in a final DMSO concentration of 1 %. Reaction were stopped after 1 h via adding 2 µl of 4 % TFA to 20 µl reaction volume. Samples were analysed on a Waters nanoAcquity coupled to a Waters SYNAPT G2- S with ESI source. The Waters nanoAcquity were equipped with a Waters Mass Prep C4, 2.1 x 5mm to desalt the samples. The nanoAcquity settings was as followed: Temperature; 65 °C, flow rate; 100 µL /min, buffer A; water / 0.1 % formic acid, buffer B; ACN / 0.1 % formic acid, run time; 6 min, gradient: in 3 min from 20% buffer B to 80%. The Waters SYNAPT G2-S were operating in ESI positive mode with the following settings: Source temperature; 80 °C, desolvation temperature; 150 °C with a desolvation gas flow rate of 500 L/hour, capillary voltage; 3 kV and cone voltage; 40V. The mass data was collected at a range of 150 m/z – 2200 m/z. Raw data were deconvoluted using MaxEnt1 from Waters. [1]
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| Cell Assay |
Cell proliferation assays [1]
Cell viability was determined by means of the AlamarBlue® reagent in a Victor X3 Multilabel Plate Reader. Cells were seeded at a concentration of 4000 cells/well in 100 µl of growth medium (RPMI1640, 20% FCS) on 96-well microtiter plates. The SK-BR-3, Au-565, H358 and MCF7 (all from ATCC), were seeded at a concentration of 5000 cells/well in 100 µl of growth medium (RPMI1640, 20% FCS) on 96-well microtiter plates. The plates were treated with various substance dilutions (3E-5 M, 1E-5 M, 3E-6 M, 1E-6 M, 3E-7 M, 1E-7 M, 3E-8 M, 1E-8 M) and incubated at 37°C for 96 hours. The IC50 values (substance concentration needed for 50% inhibition of cell proliferation) were calculated from fluorescence values of treated vs. untreated cells. |
| References | |
| Additional Infomation |
Structural mutants of p53 induce global p53 protein destabilization and misfolding, followed by p53 protein aggregation. First evidence indicates that p53 can be part of protein condensates and that p53 aggregation potentially transitions through a condensate-like state. We show condensate-like states of fluorescently labeled structural mutant p53 in the nucleus of living cancer cells. We furthermore identified small molecule compounds that interact with the p53 protein and lead to dissolution of p53 structural mutant condensates. The same compounds lead to condensation of a fluorescently tagged p53 DNA-binding mutant, indicating that the identified compounds differentially alter p53 condensation behavior depending on the type of p53 mutation. In contrast to p53 aggregation inhibitors, these compounds are active on p53 condensates and do not lead to mutant p53 reactivation. Taken together our study provides evidence for structural mutant p53 condensation in living cells and tools to modulate this process. [1]
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| Molecular Formula |
C11H8CLFN2OS
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|---|---|
| Molecular Weight |
270.710423469543
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| Exact Mass |
270.002
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| Elemental Analysis |
C, 48.81; H, 2.98; Cl, 13.10; F, 7.02; N, 10.35; O, 5.91; S, 11.84
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| CAS # |
2036352-13-1
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| PubChem CID |
165417087
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
2.8
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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 |
17
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| Complexity |
282
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| Defined Atom Stereocenter Count |
0
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| SMILES |
ClCC(NC1=NC(=CS1)C1C=CC=CC=1F)=O
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| InChi Key |
JYANOVDYYBXVNL-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C11H8ClFN2OS/c12-5-10(16)15-11-14-9(6-17-11)7-3-1-2-4-8(7)13/h1-4,6H,5H2,(H,14,15,16)
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| Chemical Name |
2-chloro-N-[4-(2-fluorophenyl)-1,3-thiazol-2-yl]acetamide
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| Synonyms |
BAY 1892005; BAY-1892005; BAY1892005; 2036352-13-1;
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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 |
| 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: 250 mg/mL (923.50 mM)
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|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.6940 mL | 18.4699 mL | 36.9399 mL | |
| 5 mM | 0.7388 mL | 3.6940 mL | 7.3880 mL | |
| 10 mM | 0.3694 mL | 1.8470 mL | 3.6940 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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