| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
WDR5-IN-4 TFA specifically targets the WIN (WDR5 interaction) site of the WD repeat domain 5 (WDR5) protein. WDR5 is a chromatin-associated scaffold protein that is essential for the recruitment and activity of MLL (mixed-lineage leukemia) histone methyltransferase complexes. The compound binds to the WIN site with a dissociation constant (Kd) of 0.1 nM, effectively blocking the protein-protein interaction between WDR5 and its partner proteins.
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| ln Vitro |
In vitro, WDR5-IN-4 TFA disrupts the binding of WDR5 to chromatin by displacing the WDR5 protein from its binding sites. This displacement leads to a reduction in the expression of WDR5-associated genes. Consequently, the compound triggers downstream cellular effects including the inhibition of protein translation and the induction of nucleolar stress, which collectively contribute to its potent anti-neoplastic activities against cancer cells.
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| ln Vivo |
Detailed in vivo efficacy data for WDR5-IN-4 TFA is not extensively covered in the provided literature summaries. However, given its potent in vitro activity and ability to disrupt WDR5 function, it is expected to be used in xenograft mouse models to evaluate its anti-cancer efficacy. Its anti-neoplastic activities are presumed to translate into the inhibition of tumor growth by blocking the expression of oncogenic drivers such as the MLL-fusion proteins.
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| Enzyme Assay |
The binding affinity of WDR5-IN-4 TFA is measured using a binding assay, such as Isothermal Titration Calorimetry (ITC) or a fluorescence polarization (FP) competition assay. In an FP assay, a fluorescently labeled WIN site peptide is incubated with purified recombinant WDR5 protein. The compound is added to compete with the peptide, causing a decrease in fluorescence polarization. The Kd value is derived from the dose-dependent inhibition of the peptide binding.
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| Cell Assay |
For cellular studies, cancer cells (e.g., MLL-rearranged leukemia cells) are treated with serial dilutions of WDR5-IN-4 TFA for 48 to 72 hours. Cell viability is measured using a luminescent CellTiter-Glo assay. Mechanistically, cells are lysed after treatment, and WDR5 chromatin displacement is assessed by chromatin immunoprecipitation (ChIP) or by a cellular WDR5-binding assay using biotinylated probes.
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| Animal Protocol |
To assess in vivo efficacy, immunocompromised mice are engrafted with human cancer cell lines that are dependent on WDR5, such as MLL-rearranged acute myeloid leukemia (AML) cells. The mice are treated with WDR5-IN-4 TFA via intraperitoneal (IP) injection or oral gavage. Tumor burden is monitored by bioluminescent imaging or by measuring tumor volume with calipers. Endpoints include survival analysis and the inhibition of tumor growth.
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| ADME/Pharmacokinetics |
Specific ADME (Absorption, Distribution, Metabolism, and Excretion) data for WDR5-IN-4 TFA is limited in the provided texts. For in vivo application, the compound can be formulated for intraperitoneal (IP) injection using a vehicle such as a mixture of DMSO and saline (e.g., 10% DMSO + 90% (20% SBE-beta-CD in Saline)). This formulation is used to assess its bioavailability and half-life in preliminary PK studies.
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| Toxicity/Toxicokinetics |
Preclinical toxicology reports for WDR5-IN-4 TFA are not provided in the summaries. It is a research compound primarily used for target validation. In cellular assays, the compound causes translational inhibition and nucleolar stress, which are mechanisms leading to cancer cell death. At efficacious doses, the expected toxicity profile would likely correlate with its on-target mechanism, but specific data is not available in this literature.
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| References | |
| Additional Infomation |
WDR5 is a promising therapeutic target in cancer, particularly in MLL-rearranged leukemias where it is essential for the activity of oncogenic MLL fusion proteins. WDR5-IN-4 TFA is a highly potent and valuable tool compound for investigating the role of the WDR5-MLL interaction in oncogenesis. By inducing translational inhibition and nucleolar stress, it represents a unique strategy for targeting transcriptionally addicted cancers. It remains in the preclinical research phase.
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| Molecular Formula |
C27H23CL2F4N5O3
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|---|---|
| Molecular Weight |
612.402837991714
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| Exact Mass |
611.111
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| CAS # |
2749300-35-2
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| Related CAS # |
WDR5-IN-4;2407457-36-5
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| PubChem CID |
146025951
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| Appearance |
Light yellow to orange solid powder
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
41
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| Complexity |
853
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC1=C(C=CC(=N1)F)C2=CC(=CC(=C2)CN3C=CN(C3=N)C)C(=O)NCC4=CC(=C(C=C4)Cl)Cl.C(=O)(C(F)(F)F)O
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| InChi Key |
SRNPJMNSZVVBDZ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C25H22Cl2FN5O.C2HF3O2/c1-15-20(4-6-23(28)31-15)18-9-17(14-33-8-7-32(2)25(33)29)10-19(12-18)24(34)30-13-16-3-5-21(26)22(27)11-16;3-2(4,5)1(6)7/h3-12,29H,13-14H2,1-2H3,(H,30,34);(H,6,7)
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| Chemical Name |
N-[(3,4-dichlorophenyl)methyl]-3-(6-fluoro-2-methylpyridin-3-yl)-5-[(2-imino-3-methylimidazol-1-yl)methyl]benzamide;2,2,2-trifluoroacetic acid
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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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| 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: ≥ 250 mg/mL (408.23 mM)
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| 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 | 1.6329 mL | 8.1646 mL | 16.3292 mL | |
| 5 mM | 0.3266 mL | 1.6329 mL | 3.2658 mL | |
| 10 mM | 0.1633 mL | 0.8165 mL | 1.6329 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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