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LEB-03-145

Alias: LEB-03-145; SCHEMBL27163858; LEB03-145; SCHEMBL-27163858;
Cat No.:V75888 Purity: ≥98%
LEB-03-145 is a WEE1 DUBTAC/deubiquitinating enzyme targeting chimera tethering adavosertib (AZD1775) to the OTUB1 recruiter EN523 via a C5 alkyl linker.
LEB-03-145
LEB-03-145 Chemical Structure CAS No.: 2858812-90-3
Product category: Wee1
This product is for research use only, not for human use. We do not sell to patients.
Size Price Stock Qty
500mg
1g
Other Sizes
Official Supplier of:
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Product Description
LEB-03-145 is a WEE1 DUBTAC/deubiquitinating enzyme targeting chimera tethering adavosertib (AZD1775) to the OTUB1 recruiter EN523 via a C5 alkyl linker.
Biological Activity I Assay Protocols (From Reference)
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

[1]. Deubiquitinase-targeting chimeras for targeted protein stabilization. Nat Chem Biol. 2022 Apr;18(4):412-421.

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]
These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
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 Data
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
(e.g. IP/IV/IM/SC)
Injection Formulation 1: DMSO : Tween 80: Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution 50 μL Tween 80 850 μL Saline)
*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 : PEG300Tween 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).
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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)]
*Preparation of 20% SBE-β-CD in Saline (4°C,1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO 100 μLPEG300 200 μL castor oil 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10: 10 : 80 (i.e. 100 μL Ethanol 100 μL Cremophor 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH 400 μLPEG300 50 μL Tween 80 450 μL 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).
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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders


Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

 (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.

Calculator

Molarity Calculator allows you to calculate the mass, volume, and/or concentration required for a solution, as detailed below:

  • Calculate the Mass of a compound required to prepare a solution of known volume and concentration
  • Calculate the Volume of solution required to dissolve a compound of known mass to a desired concentration
  • Calculate the Concentration of a solution resulting from a known mass of compound in a specific volume
An example of molarity calculation using the molarity calculator is shown below:
What is the mass of compound required to make a 10 mM stock solution in 5 ml of DMSO given that the molecular weight of the compound is 350.26 g/mol?
  • Enter 350.26 in the Molecular Weight (MW) box
  • Enter 10 in the Concentration box and choose the correct unit (mM)
  • Enter 5 in the Volume box and choose the correct unit (mL)
  • Click the “Calculate” button
  • The answer of 17.513 mg appears in the Mass box. In a similar way, you may calculate the volume and concentration.

Dilution Calculator allows you to calculate how to dilute a stock solution of known concentrations. For example, you may Enter C1, C2 & V2 to calculate V1, as detailed below:

What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:
  • Enter 10 into the Concentration (Start) box and choose the correct unit (mM)
  • Enter 25 into the Concentration (End) box and select the correct unit (mM)
  • Enter 25 into the Volume (End) box and choose the correct unit (mL)
  • Click the “Calculate” button
  • The answer of 62.5 μL (0.1 ml) appears in the Volume (Start) box
g/mol

Molecular Weight Calculator allows you to calculate the molar mass and elemental composition of a compound, as detailed below:

Note: Chemical formula is case sensitive: C12H18N3O4  c12h18n3o4
Instructions to calculate molar mass (molecular weight) of a chemical compound:
  • To calculate molar mass of a chemical compound, please enter the chemical/molecular formula and click the “Calculate’ button.
Definitions of molecular mass, molecular weight, molar mass and molar weight:
  • Molecular mass (or molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
  • Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.
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Reconstitution Calculator allows you to calculate the volume of solvent required to reconstitute your vial.

  • Enter the mass of the reagent and the desired reconstitution concentration as well as the correct units
  • Click the “Calculate” button
  • The answer appears in the Volume (to add to vial) box
In vivo Formulation Calculator (Clear solution)
Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)
Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)
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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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