| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| Other Sizes |
| Targets |
SJB3-019A targets USP1 (Ubiquitin-specific protease 1), 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 an IC50 of 0.0781 μM in K562 cells, SJB3-019A promotes ID1 degradation and induces cytotoxicity.
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| ln Vitro |
Compared to SJB2-043, SJB3-019A (IC50=0.0781 μM) had five times the potency in stimulating ID1 degradation and cytotoxicity in K562 cells. SJB3-019A lowers HR activity while raising Ub-FANCD2 and Ub-PCNA levels [1].
In vitro, SJB3-019A is a novel and potent USP1 inhibitor with an IC50 of 0.0781 μM in K562 cells. It promotes ID1 degradation and cytotoxicity. The compound triggers apoptosis in multiple myeloma cells via activation of caspase-3/8/9. It degrades USP1 and downstream inhibitor of DNA-binding proteins and inhibits DNA repair via blockade of the Fanconi anemia pathway and homologous recombination. |
| ln Vivo |
In vivo, SJB3-019A has potential for studying leukemia and related diseases. By inhibiting USP1, the compound may sensitize cancer cells to DNA-damaging agents and induce apoptosis. However, specific in vivo efficacy data and dosing details have not been extensively detailed in the available literature. Further preclinical studies would be required.
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| Enzyme Assay |
For in vitro enzyme assays, recombinant USP1 protein (often in complex with its partner UAF1) is incubated with a ubiquitinated substrate (such as ubiquitin-AMC) in assay buffer. The test compound is added at various concentrations (0.001-1000 nM). Deubiquitination activity is measured by fluorescence or by Western blotting. IC50 values are calculated by fitting dose-response curves.
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| Cell Assay |
For cell-based assays, K562 cells or multiple myeloma cells are treated with SJB3-019A at concentrations ranging from 0.01-10 µM. USP1 activity is assessed by measuring the ubiquitination status of USP1 substrates such as FANCD2 by Western blotting. ID1 degradation is assessed by Western blotting. Apoptosis is assessed by measuring caspase activity or by Annexin V staining.
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| Animal Protocol |
For in vivo efficacy studies, immunodeficient mice would be implanted with leukemia or multiple myeloma xenografts. When tumors reach a predetermined size, mice would be randomized and treated with SJB3-019A via appropriate routes at doses determined from pharmacokinetic studies. Tumor volumes would be measured twice weekly.
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| ADME/Pharmacokinetics |
SJB3-019A is soluble in DMSO (≥10.85 mg/mL) but insoluble in water and ethanol. Storage is recommended at -20°C for long-term stability. Further detailed PK parameters including half-life, oral bioavailability, and tissue distribution would be required for in vivo studies.
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| Toxicity/Toxicokinetics |
SJB3-019A is a novel and potent USP1 inhibitor with an IC50 of 0.0781 μM in K562 cells. It promotes ID1 degradation, triggers apoptosis in multiple myeloma cells, and inhibits DNA repair. SJB3-019A can be used for studying leukemia and related diseases. It is a research tool and is not approved for clinical use.
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| References |
| Molecular Formula |
C16H8N2O3
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|---|---|
| Molecular Weight |
276.24632358551
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| Exact Mass |
276.053
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| CAS # |
2070015-29-9
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| PubChem CID |
78358325
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.426±0.06 g/cm3(Predicted)
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| Boiling Point |
526.1±52.0 °C(Predicted)
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| LogP |
2.5
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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 |
21
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| Complexity |
453
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1=CC=C2C(=C1)C(=O)C3=C(C2=O)OC(=N3)C4=CN=CC=C4
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| InChi Key |
DOYPPVCQHGJUBC-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C16H8N2O3/c19-13-10-5-1-2-6-11(10)14(20)15-12(13)18-16(21-15)9-4-3-7-17-8-9/h1-8H
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| Chemical Name |
2-pyridin-3-ylbenzo[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 |
| 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 : ~10 mg/mL (~36.20 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1 mg/mL (3.62 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.6199 mL | 18.0995 mL | 36.1991 mL | |
| 5 mM | 0.7240 mL | 3.6199 mL | 7.2398 mL | |
| 10 mM | 0.3620 mL | 1.8100 mL | 3.6199 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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