CLZ-8 - 10mM in DMSO , CAS No.678158-55-9

CAS: 678158-55-9 Cat. No.: C655182 Fórmula: C₂₂H₂₃N₃O₂S Peso molecular: 393.50 PubChem CID: 988971

GRAU & PUREZA 10mM in DMSO

Storage

Store at -80°C

Shipped In

Dry ice packs + Cold packs

Visão geral

CLZ-8 (Compound 8) is an orally active Mcl-1-PUMA interface inhibitor, with a K i of 0.3 μM. CLZ-8 exhibits dual activity on reduce PUMA-dependent apoptosis while deactivating Mcl-1-mediated anti-apoptosis in cancer cells

In Vitro

CLZ-8 (Compound 8) (0-160 μM, 48 h) significantly inhibits PUMA-dependent apoptosis. CLZ-8 (0-1 μM, 2 h) significantly enhance the irradiated cell viability in a dose-dependent manner, provides significant protection for HUVECs, and inhibits overexpressed PUMA. CLZ-8 (0-1 μM, 24 h) attenuates the radiation-induced apoptosis. CLZ-8 (1 μM, 2 h) protects HUVECs from DNA breaks. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Apoptosis Analysis Cell Line: DLD-1 cells or HUVEC cells Concentration: 0-160 μM (DLD-1) or 0.01, 0.1 and 1 μM (HUVECs) Incubation Time: 48 h (DLD-1) or 24 h (HUVECs) Result: Significantly inhibited PUMA-dependent apoptosis with an IC 50 of 38.93 ± 0.91 μM. Attenuated the radiation-induced apoptosis. Western Blot AnalysisCell Line: HUVEC cells Concentration: 0.001, 0.01, 0.1 and 1 μM Incubation Time: 2 h Result: Suppressed induction of PUMA after radiation, significantly decreased the level of p53. Significantly decreased the level of MCL-1 and increased the level of Bcl-XL.

In Vivo

CLZ-8 (0-400 mg/kg; i.g.; once) shows powerful anti-radiation effects in mice. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: 6-8 week-old male BALB/c miceDosage: 100, 200 and 400 mg/kg Administration: Intragastric administration, once, 30 min prior to irradiation Result: Increased the survival rate of irradiated mice.

IC50& Target:Mcl-1 0.3 μM (Ki) PUMA

Especificações

Especificações e pureza

10mM in DMSO

Mecanismos bioquímicos e fisiológicos

CLZ-8 (Compound 8) is an orally active Mcl-1-PUMA interface inhibitor, with a K i of 0.3 μM. CLZ-8 exhibits dual activity on reduce PUMA-dependent apoptosis while deactivating Mcl-1-mediated anti-apoptosis in cancer cells.

Condições de armazenamento de armazenamento

Store at -80°C

Enviado em

Dry ice packs + Cold packs

Este produto requer transporte de cadeia fria. Serviços terrestres e outros serviços econômicos não estão disponíveis.

Nomes e identificadores

SMILES isoméricas

C1CN(CCN1CCO)C2=NC(=O)/C(=C/C3=CC=C(C=C3)C4=CC=CC=C4)/S2

PubChem CID

988971

Peso molecular

393.50

Application Protocols

No item-specific, validated protocols are provided for CLZ-8 in the Product Data.

General protocol for preparing screening stocks

• Equilibrate vial to room temperature in a desiccator.
• Quickly weigh the required amount. Prepare a 10–50 mM stock in anhydrous DMSO. Vortex and, if needed, sonicate briefly to aid dissolution.
• Sterile filtration: If required by assay, pass through a low-protein-binding 0.22 µm PTFE syringe filter into sterile, pre-labeled tubes.
• Aliquot into single-use volumes (e.g., 10–50 µL), cap tightly, and flash-freeze or place immediately at -80°C.
• For assay use, thaw once, dilute into buffer with thorough mixing to the desired final concentration while matching DMSO in control wells.

Analytical verification

• Optionally verify concentration by UV-Vis if the compound has a known extinction coefficient, or by quantitative NMR/LC-MS against an internal standard. None of these parameters are specified for this item and should be established experimentally as needed.

Biological Roles

Item-specific biological targets, pathways, or mechanisms for CLZ-8 are not provided in the Product Data.

General considerations for small-molecule library members

• Potential roles: Depending on structure, library compounds may act as enzyme inhibitors/activators, receptor ligands, ion channel modulators, or pathway probes. Any such role for CLZ-8 should be verified from primary literature or internal screening data before use as a reference compound.
• Off-target risk: Discovery-like chemotypes can display polypharmacology. Use counter-screens, orthogonal assays, and aggregation controls (e.g., detergent addition, dynamic light scattering) to de-risk artifacts.
• ADME liabilities (general): Stability in aqueous buffers, microsomal stability, and solubility/permeability can vary widely. If pursuing follow-up biology, generate basic physicochemical and stability data (solubility profile, logD7.4, chemical stability in assay buffer) specific to CLZ-8.

Research-use-only notice

• This product is intended strictly for research use. No claims are made or implied regarding biological efficacy, safety in humans or animals, or diagnostic utility.

Buffer Applications

CLZ-8 is a small-molecule screening compound, not a buffering agent. Consequently, it has no defined buffering capacity or recommended buffer systems intrinsic to the compound.

Practical guidance for using small molecules in buffers (general)

• Prepare concentrated stocks in DMSO or another suitable solvent, then dilute into assay buffer with thorough mixing. Keep final organic cosolvent low (typically ≤0.1–1% v/v) and matched in controls.
• Verify compound stability in the chosen buffer over the experimental time frame (monitor by LC-MS or HPLC). Consider pH 7.2–7.5 phosphate or HEPES buffers for routine cell-free assays unless target biology dictates otherwise.
• If precipitation occurs upon dilution, increase mixing time, warm gently to room temperature, or adjust buffer ionic strength/pH if structurally justified.

For specific buffer recipes, pH ranges, or compatibility constraints, consult assay method requirements; none are specific to this item.

Green Alternatives

Specific solvent/process hazards for CLZ-8 are not provided. For general handling of small-molecule screening compounds, consider greener choices where compatible with solubility and stability:

Comparison (general guidance)

• DMSO vs. DMF: DMSO offers favorable EHS and biodegradability profiles relative to DMF and NMP; use DMSO for stock solutions when feasible.
• 2-MeTHF or CPME vs. THF/Et2O (for extractions/workups): 2-MeTHF and CPME are less peroxide-prone and often sourced from renewables (2-MeTHF). Assess compound solubility and partitioning.
• Ethyl acetate/IPA vs. dichloromethane/chloroform: Prefer EtOAc or isopropanol in chromatographic and workup steps when separation efficiency is acceptable.
• Acetonitrile alternatives: Where HPLC allows, ethanol or aqueous methanol gradients may reduce acetonitrile use; confirm detector compatibility and peak shape.

Operational practices

• Minimize DMSO stock concentrations to what is needed for assays; aliquot to reduce waste.
• Employ microscale screening (low microliter volumes) and high-density plates to reduce solvent consumption.
• Capture and segregate halogenated vs. non-halogenated waste to maximize solvent recycling opportunities.

Pharmaceutical Uses

No pharmacopeial status, excipient role, or manufacturing use is provided for CLZ-8 in the Product Data. This item is supplied for research use only and is not intended for human or veterinary use.

General context (non-clinical)

• Screening/development: Compounds like CLZ-8 may be used in early discovery for target validation and SAR generation. Any extrapolation to formulation work should be predicated on confirmed identity, stability, and purity, and conducted under research-only conditions.
• Pre-formulation screening: If progressing toward in vivo research (not implied here), common assessments include solubility in biorelevant media, pH solubility profile, and stability in proposed vehicles. None of these data are specified for this item.

No medical, diagnostic, or therapeutic claims are made or should be inferred.

Physical Properties

Item-specific physical/analytical properties are not provided in the Product Data for CLZ-8 (CAS 678158-55-9).

• Appearance: Not specified for this item; refer to CoA/Spec Sheet.
• Melting point: Not specified for this item; refer to CoA/Spec Sheet.
• Boiling point: Not specified for this item; refer to CoA/Spec Sheet.
• Density: Not specified for this item; refer to CoA/Spec Sheet.
• Solubility: Not specified for this item; refer to CoA/Spec Sheet.
• LogP/logD: Not specified for this item; refer to CoA/Spec Sheet.
• pKa(s): Not specified for this item; refer to CoA/Spec Sheet.
• Refractive index: Not applicable to solids; if liquid, not specified for this item; refer to CoA/Spec Sheet.

General notes for small-molecule screening solids (literature/practice)

• Many discovery compounds are supplied as crystalline or amorphous solids with good solubility in anhydrous DMSO; aqueous solubility is variable and often enhanced with cosolvent (DMSO, ethanol) or pH adjustment when functional groups permit.
• If a structure is available, estimate solubility/pKa/logP using cheminformatics to plan dissolution (e.g., neutral vs. salt form) and LC-MS method development.
• Record exact solvent lot and temperature during dissolution; small differences can influence apparent solubility and stability for discovery compounds.

Always defer to the item’s CoA and stability data for authoritative specifications.

Quality and Grades

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

Context for screening compounds (general guidance)

• Discovery/screening library items are commonly provided at research grade with purity typically determined by HPLC/UPLC and identity confirmed by MS and/or NMR. Absent explicit specifications, do not assume trace-metal, water, or residual-solvent limits beyond standard research-grade expectations.
• UV/LC readiness: If HPLC purity is provided in the CoA, note the detection wavelength and method. Low-UV-absorbing impurities can be underreported at single-wavelength detection; consider PDA or ELSD if critical.
• Salt forms/hydrates: Many bioactive-like compounds are offered as free bases/acids or as salt forms to improve handling. Verify exact form (free base vs. salt, solvate/hydrate content) on the CoA, as this impacts molecular weight for dosing and solution prep.
• Stabilizers: Not specified for this item; refer to CoA/Spec Sheet. If none are listed, assume neat compound only and protect from conditions that could induce degradation (light, heat, moisture).

Documentation provided on request typically includes CoA (identity/purity), lot-specific analytical chromatogram, and, where available, NMR and MS traces.

Reaction and Applications

The Product Data categorizes CLZ-8 within a small-molecule/compound library intended for research use. No specific synthetic role or application is provided for this particular entry.

General research applications for screening compounds

• Assay screening: Use as a discrete test article in biochemical or cell-based assays for target validation, SAR exploration, or phenotypic screening. Maintain rigorous plate mapping and compound tracking to avoid cross-contamination.
• Control/reference: If literature associates CID 988971 with specific targets or pathways, it may serve as a positive/negative control—verify independently before use. In the absence of target data, treat as an exploratory hit-like molecule only.
• Analytical characterization: Prepare LC-MS and NMR samples to reconfirm identity/purity on receipt, especially for critical experiments or if reweighing indicates hygroscopicity or solvent inclusion.

Practical tips

• Prepare single-use aliquots of DMSO stock at -80°C to minimize freeze-thaw cycles and water uptake.
• For plate-based work, consider low-bind plastics and DMSO-compatible seals; equilibrate plates to room temperature in desiccated conditions before unsealing to avoid condensation.
• If employing in synthesis (e.g., as a building block), consult the structure for reactive handles and protect labile moieties during coupling or functionalization.

Reaction Conditions

No reaction conditions are specified for CLZ-8 in the Product Data. Because the chemical structure and functional groups are not provided here, specific conditions (solvents, catalysts, temperatures) cannot be tailored to this item.

General references for small-molecule derivatization (literature guidance)

• Amide coupling: HATU/DIPEA or EDCI/HOBt in DMF or DCM, 0–25°C.
• Reductive amination: NaBH3CN or BH3·THF in MeOH/THF with aldehyde/ketone, 0–25°C.
• Cross-coupling (if aryl halide present): Pd(PPh3)4 or Pd-PEPPSI catalysts; Suzuki in dioxane/H2O or DMF/H2O, 25–80°C; Buchwald–Hartwig for C–N with dialkylbiaryl phosphines.
• SNAr (if activated aryl and leaving group present): K2CO3 or Cs2CO3 in DMF/DMSO, 25–100°C.
• Hydrogenation (if reducible unsaturation): H2 (1–5 bar) over Pd/C in EtOH/EtOAc at rt–50°C.

These are general, literature-level conditions and not specific to CLZ-8. Confirm compatibility once the structure and stability data are available.

Safety and Handling

GHS and hazard specifics for this item are not provided in the Product Data.

• Signal word: Not specified for this item; refer to SDS.
• H-statements / GHS classification / pictograms: Not specified for this item; refer to SDS.

General laboratory precautions (best practice)

• Handle as a potentially hazardous small molecule. Avoid inhalation, ingestion, and skin/eye contact. Use lab coat, safety glasses, and appropriate chemically resistant gloves (e.g., nitrile). Work in a certified fume hood when weighing, dissolving, or aliquoting.
• Avoid dust/aerosol formation; gently tap or use antistatic tools when weighing dry powders.
• Storage incompatibilities: Until specific functional groups are known, segregate from strong oxidizers, strong acids/bases, and reducing agents. Protect from light and moisture unless data indicate otherwise.
• First aid overview: If inhaled—move to fresh air; if on skin—wash with soap/water; if in eyes—rinse cautiously with water for several minutes; if ingested—rinse mouth and seek medical attention. Provide SDS to medical personnel.
• Spill/cleanup: Avoid dust; absorb solutions with inert material, collect in compatible waste. Decontaminate surfaces with suitable solvent/detergent while observing compatibility.
• Waste: Dispose as organic chemical waste per institutional and local regulations.

Always consult the product-specific SDS for authoritative safety information.

Solvent Selection

Item-specific solvent compatibility for CLZ-8 is not provided. The following are general, practical guidelines for small-molecule screening compounds:

• Primary dissolution solvent: Anhydrous DMSO is the default for preparing 10–50 mM screening stocks due to broad solubilizing power and stability for many scaffolds.
• Cosolvent strategies: If aqueous use is required, prepare a DMSO concentrate and dilute into assay buffer to a final DMSO content typically ≤0.1–1% v/v, verifying assay tolerance. Ethanol or acetonitrile can be alternative cosolvents depending on assay constraints.
• pH-mediated solubility: If the compound contains ionizable groups (check structure/CoA), mildly acidic (for bases) or basic (for acids) media can enhance aqueous solubility. Avoid extreme pH unless stability is documented.
• Volatile solvents: For synthetic use or analytical sample prep, DMF, acetonitrile, methanol, or ethyl acetate may be selected based on polarity; ensure compound stability in protic vs. aprotic media before prolonged exposure.
• Water miscibility and precipitation: When diluting DMSO stocks into buffers, add slowly with mixing; consider surfactant (e.g., 0.01% Tween 80) or serum proteins if assay-compatible to mitigate precipitation for hydrophobic chemotypes.

Always verify solvent choice and concentration against the compound’s known stability/assay performance when available.

Storage and Reconstitution

• Storage conditions (from Product Data): Store at -80°C.
• Shipping (from Product Data): Shipped on dry ice packs + cold packs.

General handling guidance for small-molecule screening compounds

• Upon receipt: Keep the shipment cold; transfer immediately to a -80°C freezer. Allow vials to equilibrate to room temperature in a desiccator before opening to prevent moisture condensation.
• Stability: Specific stability data are not provided. As a precaution, minimize exposure to air, light, and moisture. Consider storing under inert gas (argon or nitrogen) if the compound is air/moisture sensitive (unknown for this item).
• Aliquoting: Prepare single-use aliquots of DMSO stocks to avoid repeated freeze–thaw cycles. Store aliquots at -80°C in tightly sealed, chemically resistant vials (e.g., PTFE-lined caps).
• Reconstitution: Solvent and concentration are not specified for this item; DMSO is commonly used for library members. If an aqueous solution is needed, dilute the DMSO stock into buffer with vigorous mixing and confirm clarity.
• Shelf life: Not specified for this item; refer to CoA/Spec Sheet. Reassess purity by LC-MS/HPLC periodically for long-term stored materials.

Research use only: Not for human or veterinary use.

Structure and Identity

• Product name: CLZ-8 (screening compound)
• CAS: 678158-55-9
• PubChem CID: 988971
• Molecular formula: Not specified for this item; refer to CoA/Spec Sheet.
• Molecular weight: Not specified for this item; refer to CoA/Spec Sheet.
• InChIKey: Not specified for this item; refer to CoA/Spec Sheet.
• SMILES: Not specified for this item; refer to CoA/Spec Sheet.

Structural features

• Item-specific structural details (functional groups, ring systems, stereochemistry) are not provided in the current Product Data. For definitive identity confirmation, consult the Certificate of Analysis (CoA), technical data sheet, or PubChem record for CID 988971.

2D structure description (general guidance)

• Without a provided structure, a textual 2D description cannot be supplied for this item. If structure is obtained, describe heteroatoms, aromatic frameworks, substituents, and any chiral centers to support method development (e.g., LC-MS transitions, NMR assignment).

Synthetic Utility

The Product Data do not include structural information for CLZ-8; therefore, specific synthetic transformations or functional-group reactivity cannot be described for this item.

General guidance if structure is available (research practice)

• Functional handles: Identify nucleophiles (amines, alcohols), electrophiles (acid chlorides, sulfonyl chlorides), π-systems (aryl halides, alkenes) to plan derivatization (e.g., amide coupling, SNAr, cross-coupling, reductive amination).
• Protecting-group strategy: If multiple reactive sites exist, select orthogonal protection to enable convergent modifications during SAR campaigns.
• Late-stage diversification: Use chemoselective methods (e.g., C–H activation, photoredox Minisci, SuFEx where motifs permit) for rapid library expansion around the CLZ-8 core.
• Analytical: Track reaction progress by LC-MS and confirm product identity with HRMS and 1D/2D NMR, given potential isomers or tautomers in heteroaromatic scaffolds.

If you require item-specific synthetic guidance, please provide or consult the structure (e.g., via PubChem CID 988971) and the CoA.

Target Specificity

No target, pathway, or selectivity information is provided for CLZ-8 in the Product Data. For screening compounds, target specificity—if any—should be established experimentally via:

• Primary assays and orthogonal confirmation.
• Counter-screens against close homologs to assess selectivity.
• Artifact controls (detergent for aggregators, redox/thiol reactivity tests, PAINS substructure checks) where applicable.

Absent validated data, treat CLZ-8 as target-agnostic.