| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| 50mg |
|
||
| Other Sizes |
| Targets |
Wu-5 targets ubiquitin-specific protease 10 (USP10). USP10 is a deubiquitinase that regulates FLT3-ITD stability. Wu-5 inhibits USP10 activity, leading to FLT3-ITD degradation through the proteasome pathway. It also inhibits FLT3 and AMPK pathways.
|
|---|---|
| ln Vitro |
FLT3-ITD-positive AML cells are specifically induced to die by Wu-5 (10 μM; 24, 48, 72 h) [1]. Apoptosis is induced in FLT3-ITD-positive AML cells by Wu-5 (1, 2.5, 5 μM; 24, 48 h) in a concentration- and time-dependent manner [1]. FLT3-ITD degradation is induced by Wu-5 (5 μM; 24 h) via the protease route [1].
Wu-5 (5 μM; 24 hours) induces FLT3-ITD degradation through the proteasome pathway. It directly interacts with and inactivates USP10 in vitro with an IC50 of 8.3 μM. Wu-5 inhibits FLT3 and AMPK pathways and induces apoptosis in FLT3-ITD-positive AML cells. |
| ln Vivo |
Wu-5 enhances crenolanib-induced FLT3-ITD-positive AML cell death via inhibiting FLT3 and AMPK pathways. In vivo activity data are limited but the compound shows promise for combination therapy in AML. Further in vivo studies in AML xenograft models are needed.
|
| Enzyme Assay |
In vitro enzyme assays measure USP10 inhibition using recombinant USP10 enzyme. IC50 values are determined by assessing deubiquitinase activity in the presence of varying concentrations of Wu-5. FLT3-ITD degradation is confirmed by immunoblotting.
|
| Cell Assay |
Cell Viability Assay[1]
Cell Types: U937, HL60, MV4-11, Molm13, and MV4-11-R cells Tested Concentrations: 10 μM Incubation Duration: 24, 48, 72 h Experimental Results: Dramatically inhibited the growth of the FLT3-ITD-positive cells (MV4-11, MV4-11-R and Molm13 cells), but had no or little effect on the proliferation of the FLT3-ITD negative cells (U937 and HL60 cells). Apoptosis Analysis[1] Cell Types: MV4-11, and Molm13 cells Tested Concentrations: 1, 2.5, 5 μM Incubation Duration: 24, 48 h Experimental Results: Induced the apoptosis of MV4-11 and Molm13 in a concentration and time-dependent manner. Western Blot Analysis[1] Cell Types: MV4-11, MV4-11-R, and Molm13 cells Tested Concentrations: 5 μM Incubation Duration: 24 h Experimental Results: Induced FLT3- ITD degradation. Cell-based assays use FLT3-ITD-positive AML cells to measure USP10 inhibition, FLT3-ITD degradation, and apoptosis induction. Western blot analysis is used to assess protein levels. Apoptosis is measured through cell viability and caspase activity assays. |
| Animal Protocol |
In vivo efficacy is evaluated in AML xenograft models. The compound's ability to inhibit tumor growth through USP10 inhibition and FLT3-ITD degradation is assessed. Combination therapy with crenolanib is also evaluated. Further studies are needed to fully characterize its in vivo activity.
|
| ADME/Pharmacokinetics |
Pharmacokinetic data for Wu-5 are limited. As a small molecule USP10 inhibitor with a molecular weight of 351.33 (C15H13NO7S), it may have favorable oral bioavailability. Further pharmacokinetic studies are needed to fully characterize its ADME properties.
|
| Toxicity/Toxicokinetics |
Preclinical toxicity data for Wu-5 are limited. As a USP10 inhibitor, its safety profile has not been fully established. Standard laboratory safety precautions should be followed. Further toxicological studies are needed for comprehensive safety assessment.
|
| References | |
| Additional Infomation |
Wu-5 is a potent USP10 inhibitor that promotes FLT3-ITD degradation and induces apoptosis in FLT3-ITD-positive AML cells. It directly interacts with and inactivates USP10 with an IC50 of 8.3 μM. Wu-5 enhances crenolanib-induced AML cell death. It is a valuable research tool for studying USP10 biology and has potential therapeutic applications in AML.
|
| Molecular Formula |
C15H13NO7S
|
|---|---|
| Molecular Weight |
351.331223249435
|
| Exact Mass |
351.041
|
| CAS # |
2630378-05-9
|
| PubChem CID |
162677550
|
| Appearance |
Off-white to light yellow solid powder
|
| LogP |
3.7
|
| Hydrogen Bond Donor Count |
0
|
| Hydrogen Bond Acceptor Count |
8
|
| Rotatable Bond Count |
7
|
| Heavy Atom Count |
24
|
| Complexity |
473
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
C1(C(OCC)=O)SC(OC2=CC=C(C(OC)=O)C=C2)=C([N+]([O-])=O)C=1
|
| InChi Key |
ZOBORTAJZNJCLJ-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C15H13NO7S/c1-3-22-14(18)12-8-11(16(19)20)15(24-12)23-10-6-4-9(5-7-10)13(17)21-2/h4-8H,3H2,1-2H3
|
| Chemical Name |
ethyl 5-(4-methoxycarbonylphenoxy)-4-nitrothiophene-2-carboxylate
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
DMSO : 25 mg/mL (71.16 mM)
|
|---|---|
| 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 | 2.8463 mL | 14.2316 mL | 28.4633 mL | |
| 5 mM | 0.5693 mL | 2.8463 mL | 5.6927 mL | |
| 10 mM | 0.2846 mL | 1.4232 mL | 2.8463 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
