WDR5-IN-4 - ≥98% , CAS No.2407457-36-5

CAS: 2407457-36-5 Cat. No.: W1429263 Formula: C₂₅H₂₂Cl₂FN₅O Molecular Weight: 498.38

GRADE & PURITY ≥98%

Storage

Store at 2-8°C

Shipped In

Wet ice

Overview

WDR5-IN-4 is an inhibitor of the WIN site of chromatin-associated WD repeat-containing protein 5 ( WDR5 ), with a K d of 0.1 nM. WDR5-IN-4 displaces WDR5 from chromatin and decreases the expression of associated genes, causing translational inhibition, nucleolar stress. Anti-cancer activity.

Specifications

Specifications & Purity

≥98%

Storage

Store at 2-8°C

Shipped In

Wet ice

This product requires cold chain shipping. Ground and other economy services are not available.

Purity

≥98%

Names and Identifiers

Molecular Weight

498.38

Application Protocols

Item-specific, validated application protocols are not provided for this product. The following represents general practice for small-molecule inhibitors in biochemical and cellular studies and should be optimized by the user.

General protocol outlines (not item-specific)

• Biochemical binding assay (TR-FRET/FP):
  1. Prepare compound stocks in DMSO (e.g., 10 mM). 2) Serially dilute in assay buffer to achieve final DMSO ≤1% v/v. 3) Incubate with WDR5 protein and labeled WIN-motif probe per kit instructions. 4) Read signal and fit concentration–response curves.
• Enzymatic assay (H3K4 methyltransferase complex):
  1. Assemble enzyme complex/cofactors. 2) Pre-incubate with compound for 15–30 min. 3) Initiate reaction with substrate and SAM. 4) Quantify methylation (radiometric, antibody-based, or MS readout).
• Cellular target engagement (CETSA/nanoBRET):
  1. Treat cells with compound across a concentration range. 2) Perform thermal shift or BRET measurements. 3) Analyze shifts relative to vehicle.

Controls and QC

• Include vehicle controls, reference active/inactive probes, and replicate wells. Verify compound integrity by LC-MS before and after assays to exclude degradation artifacts.

Note

• No Aladdin-tested applications or dilutions are claimed in this listing; optimize conditions for your system.

Biological Roles

General/literature context (not item-specific)

• WDR5 (WD repeat domain 5) is a core scaffolding component of the COMPASS/MLL/SET1 histone H3 lysine 4 (H3K4) methyltransferase complexes. It recognizes WIN-motif sequences and orchestrates assembly and activity of the methyltransferase machinery that establishes transcriptionally permissive chromatin marks (H3K4me1/2/3).
• Small-molecule WDR5 antagonists are designed to disrupt binding at the WIN site, thereby modulating complex integrity and catalytic output. As chemical tools, they enable interrogation of epigenetic regulation, transcriptional programs, and lineage-specific gene expression.

Use as a research probe

• In biochemical assays: evaluate displacement of WIN-motif peptides, changes in H3K4 methylation state, and effects on complex assembly. Complement with proteomics/ChIP-based readouts to map downstream chromatin changes.
• In cells: assess target engagement by CETSA/thermal shift, nanoBRET, or occupancy assays; monitor transcriptional consequences with RNA-seq/RT-qPCR, ensuring appropriate vehicle and inactive-analog controls.
• Selectivity profiling: benchmark against bromodomains, other WD-repeat proteins, and methyltransferase cofactors to evaluate off-target risks.

Notes and limitations

• Potency, selectivity, and permeability are compound-specific and not provided for this item. Users should generate or consult primary data for WDR5-IN-4 prior to definitive mechanistic conclusions.
• All uses are for research purposes only; no clinical or diagnostic applications are implied.

Buffer Applications

This product is a bioactive small-molecule inhibitor and is not itself a buffering agent. Consequently, classical buffer formulation guidance (pKa, buffering range) does not apply.

Practical assay-related notes (general)

• When incorporating the compound into biochemical or cellular buffers, use an appropriate vehicle (commonly DMSO) and maintain a low final organic solvent fraction (typically ≤0.5–1% v/v) to preserve protein function and cell viability.
• Compatible assay buffers often include HEPES, Tris, or phosphate systems at physiological pH with added salts and cofactors as required by the enzymatic system under study. Validate that the compound remains in solution upon dilution and does not adsorb to plastics; add 0.01–0.1% BSA or 0.01% nonionic surfactant if needed.

Item-specific buffer properties are not available; consult the CoA/Spec Sheet for any solubility notes.

Green Alternatives

Because this product is a bioactive small molecule rather than a bulk solvent or reagent, “green alternatives” pertain mainly to the choice of dissolution and processing solvents used with the compound rather than to the compound itself.

Greener solvent choices for preparation/assays (general guidance)

• Prefer water where feasible by employing cosolubilization strategies (cyclodextrins, mild surfactants) to minimize organic solvent content in assays.
• If an organic stock is required, DMSO remains common; however, consider:
  • 2-MeTHF or CPME only for synthetic steps, not typically for assay stocks.
  • Ethanol as an alternative to DMF/NMP in enzyme assays when compatible.
• Minimize solvent volumes and use microplate formats to reduce waste.

Comparison (general; not item-specific)

• DMSO: excellent solubilizer, water-miscible; environmental/health profile moderate; keep assay v/v low.
• Ethanol: renewable feedstock, lower toxicity; solubilization power often lower than DMSO for hydrophobic inhibitors.
• DMF/NMP: strong solvents but with higher health/environmental concerns; avoid in bioassays when possible.

Operational practices

• Implement solvent recycling for LC/analytical runs when infrastructure permits.
• Use closed containers and cold storage to extend shelf life of stock solutions, reducing waste due to degradation.

Pharmaceutical Uses

Item-specific regulatory status or pharmacopeial listings are not provided for this product; it is supplied strictly for research use only.

General context (not item-specific)

• WDR5 chemical probes are employed in drug discovery research to explore epigenetic target validation, structure–activity relationships (SAR), and medicinal chemistry optimization. Typical activities include potency optimization in biochemical assays, permeability/metabolic stability profiling (e.g., PAMPA, Caco-2, microsomes), and early safety panels.
• In preformulation research, small-molecule inhibitors may be characterized for solubility, lipophilicity, and solid-state form (salt/cocrystal screening) to understand developability. Such studies are internal R&D tools and do not imply suitability for clinical use.

Formulation-relevant considerations (R&D only)

• Stock solutions for screening libraries are commonly prepared in DMSO at defined concentrations (e.g., 10 mM) for automated dispensing. Aliquoting minimizes freeze–thaw cycles and potency drift.
• For in vivo exploratory studies in animals conducted under approved protocols, vehicles often combine aqueous buffers with co-solvents/surfactants; any such use must be supported by internal stability, PK, and tolerability data and is outside the scope of this catalog entry.

Compliance note

• No therapeutic, diagnostic, or GMP applications are claimed or supported. For any regulated use, source GMP-grade materials through appropriate channels.

Physical Properties

Item-specific (from Product Data)

• Appearance: Not specified for this item; refer to CoA/Spec Sheet.
• Molecular weight: Not specified for this item; refer to CoA/Spec Sheet.
• Molecular formula: Not specified for this item; refer to CoA/Spec Sheet.
• Melting point, boiling point, density, refractive index, pKa/logP, UV/Vis: Not specified for this item; refer to CoA/Spec Sheet.

General/literature guidance (not item-specific; for planning only)

• Bioactive screening compounds of this class are commonly obtained as crystalline solids or powders with limited aqueous solubility and improved solubility in polar aprotic solvents (e.g., DMSO). Exact solubility and stability profiles can vary markedly by analog and must be verified experimentally.
• If a UV chromophore is present (frequent for heteroaromatic inhibitors), analytical monitoring at 254–280 nm is often feasible; confirm with the specific spectrum for WDR5-IN-4.

Practical tips

• For initial handling, prepare small DMSO stocks (e.g., 10–50 mM), then dilute into assay buffers containing a compatible organic cosolvent (0.1–1% v/v DMSO typical), ensuring precipitation does not occur. Determine solubility limits empirically.
• Hygroscopicity, polymorphism, and solid-state stability are compound-specific; assess via TGA/DSC and repeat solubility checks after storage. Always defer to the CoA for certified item-specific values.

Quality and Grades

Item-specific (from Product Data)

• Grade/purity: Not specified for this item; refer to CoA/Spec Sheet.

Context for this product category (general guidance)

• Library/screening compounds are typically supplied at research grade with purity commonly verified by HPLC/UPLC and identity confirmed by MS and/or NMR. Chromatographic purity thresholds (e.g., ≥95% by HPLC) are common in the field but must be confirmed on the CoA for this SKU.
• Where applicable, residual solvent levels, water content (Karl Fischer), and counterion/stoichiometry for salts may be reported on the CoA. In the absence of a stated salt form, assume the neutral free base/free acid only after verification.

Implications for use

• For biochemical assays and cell-based screening, higher chromatographic purity reduces confounding off-target effects from impurities. Verify peak homogeneity and confirm identity (exact mass) before SAR conclusions.
• If your workflow is sensitive to UV background (e.g., LC-UV quantitation), request low-UV impurity data. For bioassays, endotoxin/bioburden is generally not controlled for small molecules and is usually not relevant; sterilize solutions by filtration if sterility is required.

Documentation

• For regulated environments or reproducibility requirements, retain the lot-specific CoA and any spectral data. If the grade is not specified on the label, treat the material as research use only, non-GMP.

Reaction and Applications

This item is positioned as a bioactive small molecule for research screening rather than as a synthetic reagent.

Item-specific applications (from Product Data)

• Manufacturer Applications: Not provided in the listing; no additional claims can be made beyond “For research use only.”

General/literature context (not item-specific)

• Compounds designated “WDR5 inhibitors” are typically used as chemical probes to interrogate the role of WDR5 in the COMPASS/MLL complex, modulating H3K4 methylation states in biochemical or cell-based assays. Such molecules are applied in target validation, mechanism studies, and early discovery SAR.

Practical guidance for assay use

• Verify target engagement using orthogonal assays: binding (e.g., TR-FRET, FP), biochemical methyltransferase readouts, and phenotypic endpoints (e.g., H3K4me3 levels by Western blot). Confirm on-target action via competition with WIN-motif peptides or use of WDR5 mutants.
• Titrate DMSO below levels that impact enzyme/protein stability; include appropriate vehicle controls. Assess time-dependence and reversibility where relevant.
• Establish compound handling SOPs: light protection if chromophoric, minimize freeze–thaw, and track plate map to avoid edge effects in screening.

Note

• For any claims of potency (IC50/Kd), selectivity, or cellular activity, rely on primary literature or the lot-specific CoA. No such values are provided for this item.

Reaction Conditions

Not typically applicable. WDR5-IN-4 is supplied as a research-grade small-molecule inhibitor for biological assays rather than as a reagent for chemical transformations.

General guidance for biological testing (not item-specific)

• Stock solution: Prepare in DMSO at a convenient concentration (e.g., 10 mM), vortex, and sonicate briefly if needed. Confirm clarity and absence of particulates.
• Assay concentration range: Determine empirically; typical screening spans 0.1 nM to 100 µM depending on expected potency and assay sensitivity. Include vehicle controls at matching DMSO.
• Incubation: Equilibrate with protein targets for sufficient time to reach steady state; temperature and time depend on assay format (often 15–60 min at ambient or 37°C for enzyme assays).
• Readouts: Use orthogonal methods (binding displacement, enzyme activity, thermal shift) to confirm activity. Perform triplicates and independent repeats to assess variability.

No chemical reaction solvents, catalysts, or temperature profiles are specified for this item.

Safety and Handling

Item-specific (from Product Data)

• GHS classification, signal word, hazard statements, pictograms: Not specified for this item; refer to SDS.
• Storage: Store at 2–8°C.
• Shipping: Shipped on wet ice.

General laboratory safety (not item-specific; follow institutional SOPs)

• Handle in a chemical fume hood with appropriate PPE: lab coat, safety glasses, and disposable nitrile gloves. Avoid inhalation, ingestion, and skin/eye contact. Prevent aerosol generation when weighing fine powders.
• Wash thoroughly after handling. Do not eat, drink, or smoke in work areas. Decontaminate work surfaces after use.
• Avoid incompatible materials typical for organic small molecules: strong oxidizers and strong acids/bases unless process requires them; assess compatibility prior to mixing.

First-aid overview (consult SDS for definitive instructions)

• Inhalation: Move to fresh air; seek medical attention if symptoms occur.
• Skin contact: Wash with soap and water; remove contaminated clothing.
• Eye contact: Rinse cautiously with water for several minutes; seek medical attention if irritation persists.
• Ingestion: Rinse mouth; seek medical advice.

Waste disposal

• Collect solid and liquid waste as hazardous organic waste according to local regulations. Decontaminate glassware and surfaces per institutional protocols.

Notes

• Absence of item-specific GHS data in this listing does not imply low hazard. Always consult the SDS prior to first use.

Solvent Selection

Item-specific solubility parameters are not specified for this product; consult the CoA. The guidance below reflects common practice for small-molecule inhibitors used in biochemical/cellular assays.

General solvent strategy (literature/practice)

• Stock preparation: DMSO is the default solvent for hydrophobic heteroaromatic inhibitors. Prepare concentrated stocks (e.g., 10–50 mM) to limit DMSO carryover in assays.
• Aqueous dilution: Dilute DMSO stocks into assay buffers with gentle mixing; include carrier protein (e.g., 0.01–0.1% BSA) or surfactant (e.g., 0.01% Tween-20) if non-specific adsorption or precipitation is observed.
• Alternative solvents: If DMSO is unsuitable, consider NMP, DMF, or ethanol, verifying assay compatibility and cytotoxicity. For in vitro biochemistry, maintain organic cosolvent typically ≤1% v/v.

Polarity and miscibility (general)

• DMSO: highly polar aprotic, water-miscible; excellent for stocks and serial dilutions.
• Ethanol: protic, water-miscible; may perturb protein stability at >1–2% v/v.
• PEG-400: co-solvent to increase aqueous solubility for physical studies; viscous and may affect kinetics.

Analytical considerations

• Filter sterilization (0.22 µm) can remove particulates after aqueous dilution; avoid adsorption losses by pre-wetting filters with solvent mixture.
• Verify concentration by UV/Vis, quantitative 1H NMR (qNMR), or LC-UV using a calibrant; determine extinction coefficient experimentally for precise UV quantitation.

Storage and Reconstitution

Item-specific (from Product Data)

• Storage conditions: Store at 2–8°C.
• Shipping: Shipped on wet ice.

General handling and reconstitution (not item-specific; verify with CoA/SDS)

• Upon receipt: Allow the container to equilibrate to room temperature in a desiccated environment before opening to prevent moisture condensation on the material (if supplied as a solid).
• Reconstitution: Prepare concentrated stock solutions in an appropriate solvent, typically DMSO for hydrophobic small molecules. Example practice: 10 mM stock. Mix thoroughly (vortex/brief sonication) until fully dissolved. Filter if needed using solvent-compatible 0.22 µm filters.
• Aliquoting: Dispense into single-use aliquots to minimize headspace and freeze–thaw exposure. Label with lot, concentration, and date.

Short- and long-term storage of solutions

• Absent item-specific stability data, store solutions at 2–8°C for short-term use (hours to a few days). For longer-term storage, users commonly keep DMSO stocks at −20°C or −80°C; adopt only after verifying stability by LC-MS/HPLC and activity assays for your lot.

Stability notes

• Protect from light if the compound contains UV-absorbing chromophores (common for heteroaromatics). Avoid repeated freeze–thaw cycles; thaw on ice and use promptly.

Documentation

• Refer to the lot-specific CoA and SDS for any confirmed shelf life, stability, and compatibility details not provided in this listing.

Structure and Identity

Item-specific identifiers provided: SKU W1429263; Product Name WDR5-IN-4; CAS 2407457-36-5.

Item-specific (from Product Data)

• Molecular formula: Not specified for this item; refer to CoA/Spec Sheet.
• Molecular weight: Not specified for this item; refer to CoA/Spec Sheet.
• SMILES: Not specified for this item; refer to CoA/Spec Sheet.
• InChIKey: Not specified for this item; refer to CoA/Spec Sheet.

General/literature context (not item-specific)

• WDR5-IN-4 designates a small-molecule inhibitor classically described in the epigenetics literature as targeting the WD repeat–containing protein 5 (WDR5) interaction surface within the MLL/SET1 (COMPASS) histone H3K4 methyltransferase machinery. Exact structural features of the specific “-IN-4” analog should be verified from the CoA or primary references.

Structural features (descriptive, literature-level)

• Many WDR5 antagonists feature motifs that mimic the arginine-binding “WIN” site and often present heteroaromatic rings and H-bond donor/acceptor arrays aligned to the WDR5 central cavity. However, the definitive ring systems, stereochemistry (if any), and substituent pattern for WDR5-IN-4 must be confirmed from the item’s specification sheet.

2D structure description

• Without an item-specific structure, only a generic description is possible: typical WDR5 binders are compact, heteroatom-rich small molecules designed to engage a shallow protein–protein interaction pocket. Please consult the product CoA/SDS for the exact 2D structure and identifiers.

Synthetic Utility

This product is intended as a bioactive screening compound rather than a synthetic building block or reagent. Consequently, it is not typically used as a synthon, ligand, catalyst, or stoichiometric reagent in preparative chemistry.

General/literature observations (not item-specific)

• Many WDR5 inhibitors contain multiple heteroatoms and privileged motifs engineered for protein binding; such structures can be valuable references for medicinal chemistry but are not commonly deployed as intermediates.
• If structural analogs are to be prepared, retrosynthetic analysis usually targets modular installation of heteroaromatic cores, amide/urea linkages, or guanidinium/arginine-mimetic fragments that interact with the WDR5 WIN site. However, the precise disconnections depend entirely on the disclosed structure of the specific analog and are not provided for this item.

Recommendation

• For synthetic campaigns, consult primary literature patents/articles describing WDR5 antagonists, using WDR5-IN-4 only as a biological reference point. This catalog entry does not provide structural or reactivity specifications for use in synthesis.

Target Specificity

Item-specific data

• Target, potency (IC50/Kd), selectivity panel results, and off-target profiles: Not specified for this item; refer to CoA/Spec Sheet or primary literature.

General/literature context (not item-specific)

• Compounds labeled as WDR5 inhibitors are designed to bind the WIN site of WDR5, disrupting interactions within the MLL/SET1 (COMPASS) complex. Selectivity versus other WD-repeat proteins and epigenetic targets must be empirically determined.

Recommendations

• Confirm target engagement for your lot using at least two orthogonal assays (e.g., TR-FRET peptide displacement and CETSA/nanoBRET in cells).
• Benchmark against known reference probes (active and inactive analogs) and include specificity controls (mutant WDR5 or competition with WIN peptides) to validate on-target effects.
• For any SAR or mechanistic claims, rely on verified, lot-specific data; none are provided in this listing.