| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
LEB-03-145 targets the deubiquitinase OTUB1 (via covalent binding to C23) and the tumor suppressor kinase WEE1 (via AZD1775 warhead)
|
|---|---|
| ln Vitro |
LEB-03-145 stabilizes WEE1 protein levels in HEP3B hepatoma cells. At 10 μM, it significantly increased WEE1 abundance, comparable to the proteasome inhibitor bortezomib (Extended Data Figure 15c-d). No inhibition of OTUB1 catalytic activity was observed, confirming allosteric recruitment [1]
|
| Enzyme Assay |
OTUB1 Engagement Assay: Recombinant OTUB1 protein was incubated with LEB-03-145 or controls, followed by IA-rhodamine probe labeling. Gel-based ABPP confirmed compound engagement at OTUB1 C23 without inhibiting catalytic activity toward K48-linked di-ubiquitin substrates [1]
|
| Cell Assay |
WEE1 Stabilization Assa: HEP3B cells were treated with 10 μM LEB-03-145, EN523 (OTUB1 recruiter), AZD1775 (WEE1 ligand), or DMSO for 24 hours. Cells were lysed, proteins separated by SDS-PAGE, and WEE1 levels detected by western blot using anti-WEE1 antibody. Quantification showed >3-fold increase in WEE1 compared to controls [1]
|
| References | |
| Additional Infomation |
LEB-03-145 is a heterobifunctional DUBTAC (Deubiquitinase-Targeting Chimera) linking the covalent OTUB1 recruiter EN523 to the WEE1 inhibitor AZD1775 via a C5 alkyl linker. It demonstrates proof-of-concept for targeted stabilization of tumor suppressors degraded via ubiquitin-proteasome pathways [1]
|
| Molecular Formula |
C45H55N11O6
|
|---|---|
| Molecular Weight |
846
|
| Exact Mass |
845.4336785
|
| CAS # |
2858812-90-3
|
| PubChem CID |
162624802
|
| Appearance |
Typically exists as solid at room temperature
|
| LogP |
4.1
|
| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
13
|
| Rotatable Bond Count |
18
|
| Heavy Atom Count |
62
|
| Complexity |
1550
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
CC(C)(C1=NC(=CC=C1)N2C3=NC(=NC=C3C(=O)N2CC=C)NC4=CC=C(C=C4)N5CCN(CC5)CCCCCNC(=O)CCC6=CC=C(O6)N7CCN(CC7=O)C(=O)C=C)O
|
| InChi Key |
XLHADJZHJGTTFK-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C45H55N11O6/c1-5-22-55-43(60)35-30-47-44(50-42(35)56(55)37-12-10-11-36(49-37)45(3,4)61)48-32-13-15-33(16-14-32)52-26-24-51(25-27-52)23-9-7-8-21-46-38(57)19-17-34-18-20-41(62-34)54-29-28-53(31-40(54)59)39(58)6-2/h5-6,10-16,18,20,30,61H,1-2,7-9,17,19,21-29,31H2,3-4H3,(H,46,57)(H,47,48,50)
|
| Chemical Name |
N-[5-[4-[4-[[1-[6-(2-hydroxypropan-2-yl)pyridin-2-yl]-3-oxo-2-prop-2-enylpyrazolo[3,4-d]pyrimidin-6-yl]amino]phenyl]piperazin-1-yl]pentyl]-3-[5-(2-oxo-4-prop-2-enoylpiperazin-1-yl)furan-2-yl]propanamide
|
| Synonyms |
LEB-03-145; SCHEMBL27163858; LEB03-145; SCHEMBL-27163858;
|
| 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
|
|---|---|
| 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 | 1.1820 mL | 5.9102 mL | 11.8203 mL | |
| 5 mM | 0.2364 mL | 1.1820 mL | 2.3641 mL | |
| 10 mM | 0.1182 mL | 0.5910 mL | 1.1820 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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