| Size | Price | Stock | Qty |
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| 5mg |
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| Other Sizes |
| Targets |
USP1-IN-2 targets ubiquitin-specific protease 1 (USP1), a deubiquitinating enzyme that removes ubiquitin moieties from target proteins. USP1 plays a critical role in the DNA damage response, particularly in the Fanconi anemia pathway and translesion synthesis, by deubiquitinating FANCD2 and PCNA. By inhibiting USP1 with high potency (IC50 <50 nM), USP1-IN-2 prevents deubiquitination of these targets, leading to impaired DNA repair and increased sensitivity to DNA-damaging agents.
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| ln Vitro |
In vitro, USP1-IN-2 inhibits USP1 with an IC50 of less than 50 nM. It has potential anti-tumor activity. By inhibiting USP1, the compound increases the ubiquitination of USP1 substrates such as FANCD2 and PCNA, disrupting DNA repair pathways and sensitizing cancer cells to DNA-damaging agents. The compound's potent USP1 inhibition makes it a valuable tool for studying the role of USP1 in cancer cell survival and DNA repair.
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| ln Vivo |
In vivo, USP1-IN-2 has potential anti-tumor activity for the study of cancer. By inhibiting USP1, the compound may sensitize tumors to chemotherapy and targeted therapies. However, specific in vivo efficacy data for USP1-IN-2 have not been detailed in the available literature. Preclinical studies in xenograft models would be required to assess its anti-tumor efficacy, tolerability, and pharmacokinetic properties.
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| Enzyme Assay |
For in vitro deubiquitinase assays, recombinant USP1 protein (often in complex with its partner UAF1) is incubated with a ubiquitinated substrate (such as ubiquitin-AMC or a ubiquitinated protein) in assay buffer. The test compound is added at various concentrations (typically 0.001-100 µM). Deubiquitination activity is measured by the release of free ubiquitin, which can be detected by fluorescence (for ubiquitin-AMC) or by Western blotting (for ubiquitinated protein substrates). IC50 values are calculated by fitting dose-response curves.
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| Cell Assay |
For cell-based assays, cancer cell lines are treated with USP1-IN-2 at concentrations ranging from 0.01-10 µM for various time points. USP1 activity is assessed by measuring the ubiquitination status of USP1 substrates such as FANCD2 and PCNA by Western blotting. Cell viability and proliferation are measured using MTT, CCK-8, or CellTiter-Glo assays. The compound's ability to sensitize cells to DNA-damaging agents such as cisplatin, mitomycin C, or PARP inhibitors can be evaluated in combination studies.
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| Animal Protocol |
For in vivo efficacy studies, immunodeficient mice would be implanted with cancer cell lines that are sensitive to USP1 inhibition. When tumors reach a predetermined size, mice would be randomized to receive USP1-IN-2 via oral or intraperitoneal administration at doses determined from pharmacokinetic studies. Tumor volumes would be measured twice weekly. Combination studies with DNA-damaging agents or PARP inhibitors can be performed to evaluate synergistic effects. At study endpoint, tumors would be collected for Western blot analysis of USP1 substrates.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of USP1-IN-2 have not been characterized in the available literature. The compound has a molecular weight of 510.49 g/mol, suggesting potential for drug-like properties. Standard PK studies including solubility, permeability, half-life, oral bioavailability, and tissue distribution would be required to support in vivo studies. The compound is typically stored at -20°C for long-term stability.
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| Toxicity/Toxicokinetics |
Toxicological data for USP1-IN-2 have not been reported. As a research compound, it is intended for laboratory use only and is not for human or veterinary use. Standard safety precautions should be followed when handling this compound. Comprehensive toxicology studies would be required before any clinical development.
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| References | |
| Additional Infomation |
USP1-IN-2 (Compound I-193) is a potent USP1 inhibitor with an IC50 of less than 50 nM. It has potential anti-tumor activity for cancer research. USP1-IN-2 inhibits the deubiquitinase USP1, which plays a role in DNA damage repair and other cellular processes, making it promising for sensitizing cancer cells to chemotherapy and targeted therapies. It is a research tool and is not approved for clinical use.
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| Molecular Formula |
C26H22F4N6O
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|---|---|
| Molecular Weight |
510.49
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| Exact Mass |
510.179
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| CAS # |
2098212-05-4
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| PubChem CID |
129140207
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| Appearance |
White to off-white solid powder
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| LogP |
4.4
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
37
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| Complexity |
806
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| Defined Atom Stereocenter Count |
0
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| SMILES |
N1C2C(=NC(C3=CC=CC(F)=C3C(C)C)=NC=2)N(CC2=CC=C(C3N(C)C=C(C(F)(F)F)N=3)C=C2)C1=O
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| InChi Key |
DCXQZTACMIBGMC-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C26H22F4N6O/c1-14(2)21-17(5-4-6-18(21)27)22-31-11-19-24(34-22)36(25(37)32-19)12-15-7-9-16(10-8-15)23-33-20(13-35(23)3)26(28,29)30/h4-11,13-14H,12H2,1-3H3,(H,32,37)
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| Chemical Name |
2-(3-fluoro-2-propan-2-ylphenyl)-9-[[4-[1-methyl-4-(trifluoromethyl)imidazol-2-yl]phenyl]methyl]-7H-purin-8-one
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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 : ~62.5 mg/mL (~122.43 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.07 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 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 20.8 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9589 mL | 9.7945 mL | 19.5890 mL | |
| 5 mM | 0.3918 mL | 1.9589 mL | 3.9178 mL | |
| 10 mM | 0.1959 mL | 0.9795 mL | 1.9589 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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