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| 10mg |
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| 100mg |
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| Targets |
C527 targets deubiquitinating enzymes (DUBs), with its highest potency against the USP1/UAF1 complex (IC₅₀ = 0.88 μM). It also inhibits USP5. By inhibiting USP1/UAF1, C527 prevents the deubiquitination of substrates such as FANCD2 and FANCI, leading to their accumulation in ubiquitinated forms. This disrupts DNA repair pathways and induces cell death in cancer cells. C527's mechanism makes it a valuable tool for studying the role of deubiquitination in cancer and DNA repair.
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| ln Vitro |
Cutting USP1/UAF1 with C527 results in a 0.88±0.03 μM IC50, which decreases the enzyme's enzymatic activity. USP12/USP46 complex and other DUB enzymes' DUB activity is inhibited in vitro by C527. When compared to the USP1/UAF1 complex, C527's IC50 for these DUB enzymes is greater. A factor of less is used to block the distinct DUB enzyme subtypes UCH-L1 and UCH-L3. Ub-FANCD2 and Ub-FANCI levels rose after receiving C527 therapy. Mitomycin C and camptothecin cytotoxicity was increased when cells were pretreated with C527. Reduction of homologous recombination activity and purification of DNA damage-sensitive cells are caused by an increase in ubiquitinated versions of FANCD2 and FANCI following C527 therapy [1].
In vitro, C527 is a pan-DUB enzyme inhibitor with high potency for the USP1/UAF1 complex (IC₅₀ = 0.88 μM). It also inhibits USP5. C527 shows lower inhibition of UCH-L1 and UCH-L3. Treatment with C527 leads to increased levels of Ub-FANCD2 and Ub-FANCI. In cell-based assays, C527 treatment results in accumulation of ubiquitinated proteins, disruption of DNA repair, and induction of apoptosis in cancer cells. These studies confirm the compound's mechanism as a DUB inhibitor. |
| ln Vivo |
In vivo, C527 has been studied for its potential in cancer therapy. By inhibiting deubiquitinating enzymes, particularly USP1/UAF1, C527 disrupts DNA repair pathways and induces cell death in cancer cells. However, detailed in vivo efficacy data are limited. The compound is primarily used as a research tool in in vitro studies of deubiquitination and DNA repair. Comprehensive in vivo studies are needed to fully characterize its therapeutic potential.
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| Enzyme Assay |
In vitro enzyme assays for C527 involve measuring its inhibition of deubiquitinating enzyme (DUB) activity. The enzyme is incubated with a ubiquitinated substrate and varying concentrations of C527. The cleavage of the ubiquitin moiety from the substrate is measured, and the IC₅₀ is calculated. The compound's potency against USP1/UAF1 (IC₅₀ = 0.88 μM), USP5, UCH-L1, and UCH-L3 is assessed using specific substrates. These assays confirm the compound's mechanism as a pan-DUB inhibitor.
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| Cell Assay |
In vitro cell-based assays for C527 evaluate its effects on deubiquitination and DNA repair. Cells are cultured and treated with C527, and ubiquitinated protein levels are assessed by Western blot using ubiquitin-specific antibodies. DNA repair is assessed by measuring the levels of Ub-FANCD2 and Ub-FANCI, which are substrates of USP1/UAF1. Cell viability and apoptosis are assessed using MTT or flow cytometry. These assays confirm the compound's functional activity as a DUB inhibitor.
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| Animal Protocol |
In vivo animal experiments for C527 have not been extensively reported. The compound is primarily used as a research tool in in vitro studies of deubiquitination and DNA repair. For potential in vivo studies, C527 can be administered via intraperitoneal injection in mouse xenograft models of cancer. Tumor growth and DNA repair markers would be assessed. Comprehensive in vivo studies are needed.
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| ADME/Pharmacokinetics |
Pharmacokinetic (PK) data for C527 are limited. The compound has a molecular weight of 293.25 g/mol and a molecular formula of C₁₇H₈FNO₃【48†4-L5】【48†8】【48†24】. It is a tricyclic small molecule. The compound's metabolic stability, half-life, and bioavailability have not been fully characterized. Comprehensive ADME studies are needed.
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| Toxicity/Toxicokinetics |
The toxicity profile of C527 has not been extensively characterized. As a research compound, it should be handled with appropriate safety precautions. The compound is for research use only and is not intended for human or veterinary use. Comprehensive toxicological studies are needed to fully characterize the safety profile of C527.
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| References | |
| Additional Infomation |
C527 is a pan-deubiquitinating enzyme (DUB) inhibitor with high potency for the USP1/UAF1 complex (IC₅₀ = 0.88 μM). It also inhibits USP5. C527 treatment leads to increased levels of Ub-FANCD2 and Ub-FANCI. It has a molecular formula of C₁₇H₈FNO₃ and a molecular weight of 293.25 g/mol. C527 is a research tool for studying deubiquitination and DNA repair and has not progressed to clinical trials.
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| Molecular Formula |
C17H8NO3F
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| Molecular Weight |
293.249
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| Exact Mass |
293.048
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| CAS # |
192718-06-2
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| PubChem CID |
2307331
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
488.6±47.0 °C at 760 mmHg
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| Flash Point |
249.3±29.3 °C
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| Vapour Pressure |
0.0±1.2 mmHg at 25°C
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| Index of Refraction |
1.639
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| LogP |
4.82
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
22
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| Complexity |
475
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
ULJDFEYQOPCCPM-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C17H8FNO3/c18-10-7-5-9(6-8-10)17-19-13-14(20)11-3-1-2-4-12(11)15(21)16(13)22-17/h1-8H
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| Chemical Name |
2-(4-fluorophenyl)benzo[f][1,3]benzoxazole-4,9-dione
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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 Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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) |
H2O : ~1 mg/mL (~3.41 mM)
DMSO : ~1 mg/mL (~3.41 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 | 3.4101 mL | 17.0503 mL | 34.1006 mL | |
| 5 mM | 0.6820 mL | 3.4101 mL | 6.8201 mL | |
| 10 mM | 0.3410 mL | 1.7050 mL | 3.4101 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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