| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Targets |
I-138 targets the USP1-UAF1 deubiquitinase complex. USP1 is a deubiquitinating enzyme that, when complexed with its cofactor UAF1, removes ubiquitin from specific substrates, including FANCD2 and PCNA. This complex plays a critical role in the DNA damage response and in the regulation of cell proliferation. By inhibiting USP1-UAF1, I-138 stabilizes the ubiquitinated forms of its substrates, disrupting DNA repair and cell cycle progression.
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| ln Vitro |
In vitro, I-138 is a highly potent and reversible inhibitor of USP1-UAF1 with an IC50 of 4.1 nM and a Ki of 5.4 nM. It induces the monoubiquitination of FANCD2 and PCNA in MDA-MB-436 cells and increases PCNA and FANCD2 monoubiquitination in HAP-1 USP1 WT cells. It exhibits mutually exclusive binding with ML323 and synergistic binding with ubiquitin.
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| ln Vivo |
In vivo, I-138 is being investigated for its potential to treat autoimmune disorders, chronic inflammation, and other immune-related diseases. Its oral activity makes it a promising candidate for therapeutic development. However, specific in vivo efficacy data is not detailed in the available literature.
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| Enzyme Assay |
The inhibitory activity of I-138 is assessed using in vitro deubiquitinase assays. Recombinant USP1-UAF1 complex is incubated with a ubiquitinated substrate and varying concentrations of the compound. The deubiquitination reaction is measured, and the IC50 is calculated.
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| Cell Assay |
The cellular activity of I-138 is evaluated in various cell lines. Cells are treated with I-138, and its effect on the ubiquitination of FANCD2 and PCNA is measured by Western blot. Its effect on cell proliferation, DNA repair, and signaling pathways is also assessed.
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| Animal Protocol |
In animal studies, I-138 would be administered orally to rodent models of autoimmune or inflammatory diseases. Its effect on disease severity, immune cell function, and inflammatory markers would be assessed.
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| ADME/Pharmacokinetics |
As an orally active small molecule (MW 492.50, C26H23F3N6O), I-138 is designed for convenient administration. Its pharmacokinetic properties, such as oral bioavailability and half-life, are suitable for in vivo studies.
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| Toxicity/Toxicokinetics |
Toxicology data for I-138 is limited. As a research compound, its safety profile has not been established in formal toxicology studies. However, its oral activity and mechanism of action suggest it would be a candidate for further development.
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| References | |
| Additional Infomation |
I-138 (CAS: 2098211-50-6) is a highly potent and selective inhibitor of the USP1-UAF1 deubiquitinase complex. Its oral activity and reversible inhibition make it a valuable tool for studying the role of this complex in DNA repair and disease. It holds potential for treating autoimmune disorders, chronic inflammation, and cancer.
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| Molecular Formula |
C26H23F3N6O
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|---|---|
| Exact Mass |
492.188
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| CAS # |
2098211-50-6
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| Related CAS # |
2098211-50-6
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| PubChem CID |
129139687
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| Appearance |
White to light yellow solid
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| LogP |
4.3
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
36
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| Complexity |
773
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC(C)C1=CC=CC=C1C2=NC=C3C(=N2)N(C(=O)N3)CC4=CC=C(C=C4)C5=NC(=CN5C)C(F)(F)F
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| InChi Key |
MVCJEDLGJGHLJM-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C26H23F3N6O/c1-15(2)18-6-4-5-7-19(18)22-30-12-20-24(33-22)35(25(36)31-20)13-16-8-10-17(11-9-16)23-32-21(14-34(23)3)26(27,28)29/h4-12,14-15H,13H2,1-3H3,(H,31,36)
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| Chemical Name |
9-[[4-[1-methyl-4-(trifluoromethyl)imidazol-2-yl]phenyl]methyl]-2-(2-propan-2-ylphenyl)-7H-purin-8-one
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| Synonyms |
I-138
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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: ~100 mg/mL (~203.1 mM; with ultrasonication)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (5.08 mM) 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; with ultrasonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of DMSO stock solution (25.0 mg/mL) to 400 μL of PEG300 and mix well; then add 50 μL of Tween-80 and mix well; finally add 450 μL of physiological saline and 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 (5.08 mM) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), Clear solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of DMSO stock solution (25.0 mg/mL) to 900 μL of corn oil and mix well. (Please use freshly prepared in vivo formulations for optimal results.) |
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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