CNS-Penetrant Compound Library

Cat. No.: Lib412051

Storage

Room temperature

개요

• A unique collection of 645 small molecule compounds with biological activity used for neurologic research and associated assays

•Targets 5-HT Receptor, DHFR, COX, RAAS, AChR, etc

• Some compounds have been approved by the FDA

• Structurally diverse, medicinally active, and cell permeable

• Rich documentation with structure, IC50, and customer reviews

• NMR and HPLC validated to ensure the highest purity
Product Details

Formulation	588 compounds pre-dissolved in 10mM DMSO，38 compounds pre-dissolved in 10mM H2O,17 compounds pre-dissolved in 2mM DMSO，2 compounds pre-dissolved in 2mM H2O
Container	96 Well Format Sample Storage Tube With Screw Cap and Optional 2D Barcode
Stability	12 months -20°C in DMSO
	24 months -80°C in DMSO
Shipping	Blue ice or dry ice

CNS-Penetrant Compound Library Composition

Specifications

보관 조건

Room temperature

Application Protocols

No item-specific protocols, plate maps, or concentrations are provided in the Product Data for this SKU. Refer to CoA/Spec Sheet.

General HTS/HCS workflow for CNS-penetrant libraries (not item-specific):

• Receipt and inventory:
  • Verify plate barcodes and integrity; equilibrate to room temperature before unsealing to minimize condensation.
• Dilution and plating:
  • Prepare intermediate daughter plates to limit freeze–thaw. Target final assay vehicle (e.g., DMSO) ≤0.1–1% v/v as tolerated by your system.
• Controls:
  • Include vehicle controls on every plate; add known positive controls if available for the target/pathway; use inter-plate standards to correct for drift.
• Assay execution:
  • Use automated pipetting for consistency; randomize well positions to de-bias edge effects; incorporate plate sealing to limit evaporation.
• Data quality:
  • Monitor Z′ factor, signal window, and coefficient of variation; flag and retest outliers. Confirm hits with concentration–response curves and orthogonal readouts.
• Post-screen triage:
  • Remove aggregators/fluorescence interferers; reconfirm actives from fresh material and assess purity by LC–MS before SAR.

These steps are provided as general guidance to facilitate robust screening.

Biological Roles

As a collection, the library does not have a single biological role. It is intended to provide chemical matter enriched for properties associated with CNS exposure in research models.

General background (literature):

• CNS penetration is governed by a combination of passive diffusion across the BBB, active transporter interactions, and efflux (notably P-glycoprotein and BCRP). Physicochemical features—balanced lipophilicity, limited polarity, and low H-bond donor count—modulate these processes.
• Common pharmacological classes represented in CNS-relevant chemical space include ligands for GPCRs, ion channels, transporters, and enzymes involved in neurotransmitter synthesis/degradation.
• Early triage frequently includes:
  • Permeability assays (PAMPA-BBB, MDCK-MDR1), metabolic stability (microsomes/hepatocytes), and CNS MPO (multiparameter optimization) scoring to estimate brain exposure potential.
  • Counterscreens for cytotoxicity in neuronal and glial lines to evaluate therapeutic index windows during discovery.

Use case orientation:

• The library serves as starting chemical matter for discovering tool compounds and probes for CNS biology. Any observed activities require confirmation, orthogonal validation, and full safety profiling before use as research probes.

Note: No clinical or therapeutic claims are made. Item-specific biological targets or activities are Not specified for this item; refer to CoA/Spec Sheet.

Buffer Applications

Not directly applicable to a compound library. Buffers are selected according to the biological assay being run rather than by the library itself.

General guidance (not item-specific):

• Enzymatic assays: choose buffers that maintain enzyme stability and avoid chelating/denaturing components where metal ions or cofactors are required.
• Cell-based assays: use physiological buffers/media (e.g., HEPES-buffered media at pH 7.3–7.4) and limit vehicle concentrations (e.g., DMSO ≤0.1–1% v/v as tolerated).
• BBB models: for Transwell assays, ensure matched osmolarity and pH across apical/basolateral chambers; include serum proteins only if validated for your readout.

For detailed buffer recipes and compatibility, follow your assay SOPs; no item-specific buffer recommendations are provided for this SKU.

Green Alternatives

While a compound library itself is not a process solvent or reagent, greener screening practices can substantially reduce environmental impact.

Opportunities (general, not item-specific):

• Solvent minimization:
  • Reduce DMSO concentration in assays where feasible; employ miniaturization (e.g., 384–1536-well formats) to cut solvent and consumables.
• Plate handling:
  • Use low-evaporation seals and reuse racks where validated to reduce plastic waste.
• Analytical workflows:
  • Favor UHPLC with short gradients and low-flow ESI to cut acetonitrile consumption; consider aqueous-compatible HILIC/RP methods.
• Shipping/storage:
  • Consolidate shipments, select ambient-stable formats when possible, and optimize cold-chain only when necessary (this SKU lists Room temperature storage in Product Data).

Comparison of solvent vehicles (general):

• DMSO (common): excellent solvency; environmental and health considerations warrant minimization and proper waste disposal.
• 2-Methyltetrahydrofuran or Cyrene (for synthetic prep, not typical for screening vehicles): greener than DMF/NMP; may aid in resynthesis campaigns when advancing hits.

Quality-by-design for green screening:

• Early assessment of solubility/permeability reduces iterative re-testing and waste.
• Implement computational triage to down-select compounds before wet assays, reducing reagent and energy consumption.

Pharmaceutical Uses

Not applicable for direct pharmaceutical formulation. This product is for research use only (as stated in Product Data) and is intended for early discovery screening.

General, non-clinical context:

• Early discovery role: identification of hit matter with physicochemical properties compatible with CNS exposure in preclinical models.
• Developability profiling: post-hit, evaluate solubility, permeability, metabolic stability, and efflux liability to inform medicinal chemistry.
• No pharmacopeial status or excipient role is implied for this library.

Any advancement toward formulated drug candidates requires extensive optimization and safety assessment beyond the scope of this product.

Physical Properties

As a multi-compound library, unified physical property values do not apply.

• Item-specific data from Product Data:
  • Appearance: Not specified for this item; refer to CoA/Spec Sheet.
  • Molecular Weight (single value): Not applicable to a library
  • Density, BP/MP, refractive index, UV cutoff, water/peroxide/metal limits: Not specified for this item; refer to CoA/Spec Sheet.

General/literature context for CNS-focused small molecules (not item-specific):

• Typical single-compound properties within CNS space:
  • Molecular weight: commonly 250–450 Da (literature)
  • cLogP: often 2.0–4.0 (literature)
  • TPSA: often ≤60–90 Ų; lower TPSA favors passive BBB diffusion (literature)
  • pKa: preference for neutral species at pH 7.4 to avoid P-gp efflux; weak bases frequently represented (literature)
• Solubility considerations:
  • CNS-like chemotypes may show moderate aqueous solubility; solubilization often relies on DMSO stocks with buffer dilution for assays (general practice).
• Format notes (general, not item-specific):
  • Screening libraries are commonly supplied as dry films in microplates or as DMSO solutions (e.g., 10 mM) for HTS; exact format, volumes, and concentrations are Not specified for this item; refer to CoA/Spec Sheet.

For any per-compound physical data, quality metrics, or plate-specific concentrations, please consult the accompanying documentation for SKU Lib412051.

Quality and Grades

• Item-specific grade/purity from Product Data:
  • Grade/Purity: Not specified for this item; refer to CoA/Spec Sheet.

How quality is typically defined for screening libraries (general; not item-specific claims):

• Identity confirmation: LC–MS (accurate mass), MS/MS library matching, and/or 1H NMR on representative lots.
• Purity thresholds: often ≥90–95% by LC–UV/MS at multiple wavelengths; salts and counterions reported where applicable.
• Format QC: verification of plate maps, barcodes, well volumes, and absence of cross-well contamination; spot checks for water content in DMSO solutions.
• Stability: re-test intervals (e.g., 6–12 months) with LC–MS to monitor degradation and precipitates, especially for sensitive chemotypes (e.g., aldehydes, acid chlorides, anilines prone to air oxidation).
• Documentation typically provided (consult CoA/Spec Sheet for this SKU):
  • Compound list with identifiers, lot numbers, purities, and analytical methods
  • Plate layout (CSV/SD file), concentrations, and solvent composition (if in solution)
  • Handling notes (e.g., recommended dilution and storage life)

Interpretation for end-users:

• Heterogeneous libraries demand per-compound scrutiny prior to hit advancement. Confirm identity/purity of screening positives with fresh analytical data and, where possible, resynthesize or repurchase for orthogonal confirmation.

Reaction and Applications

This product is intended for discovery screening rather than as a single reagent for chemical synthesis.

• Item-specific applications from Manufacturer Applications: Not specified for this item; refer to CoA/Spec Sheet.

Discovery applications (general for CNS-penetrant libraries):

• Target-based screening: enzymatic or binding assays for CNS-relevant proteins (e.g., CNS ion channels, GPCRs, kinases, transporters), measuring activity across concentration-response.
• Phenotypic assays: neurite outgrowth, synaptic function reporters, neuronal survival/toxicity, microglia activation, or blood–brain barrier (BBB) model permeability.
• ADME triage: parallel assessment of solubility, passive permeability (PAMPA/MDCK), microsomal stability, and P-gp/BCRP efflux to prioritize CNS-suitable hits.
• Orthogonal profiling: counterscreens for pan-assay interference compounds (PAINS), redox cyclers, aggregators, and fluorescent quenchers to reduce false positives.

Practical tips (general):

• Thaw-and-use strategy minimizes freeze–thaw cycles; maintain humidity control to limit DMSO water uptake if in solution.
• Normalization: include vehicle-only and positive-control wells; use inter-plate controls to correct for drift.
• Hit confirmation: re-order or re-synthesize top hits; confirm identity/purity by LC–MS/1H NMR prior to SAR.

Note: No specific reaction chemistry guidance applies here since the product is not a single chemical reagent.

Reaction Conditions

Not applicable. This SKU is not a reagent used in a specific chemical transformation. No unified reaction conditions pertain to the library.

General downstream practices following screening hits (literature guidance):

• Analogue synthesis often employs mild cross-coupling in polar aprotic solvents (e.g., dioxane, toluene, MeCN) with Pd catalysts at 50–120°C; base and ligand selection tailored to scaffold.
• Functional group interconversions (amide formation, carbamate/urea installation) proceed under standard coupling conditions (EDC/HATU/acid chloride routes) with attention to sterics and basicity to preserve CNS-suitable properties.
• Optimization cycles integrate microsomal stability and permeability assays to guide substituent and scaffold choices.

These are general medicinal chemistry practices and are not specifications for this product.

Safety and Handling

• Item-specific hazard information from Product Data:
  • Signal Word: Not specified for this item; refer to SDS.
  • H-Statements: Not specified for this item; refer to SDS.
  • GHS Classification: Not specified for this item; refer to SDS.
  • Pictograms: Not specified for this item; refer to SDS.

Best-practice guidance for compound libraries (general, not item-specific):

• Treat as a mixture of research chemicals with unknown comprehensive toxicology. Use in a chemical fume hood and avoid aerosolization or skin contact.
• PPE: lab coat, safety glasses, and appropriate chemical-resistant gloves; change gloves frequently when handling plates or concentrated stocks.
• If supplied in DMSO (common for libraries), avoid skin contact due to transdermal transport potential of solutes; clean spills with absorbent pads and detergent, then water rinse.
• Incompatibilities: segregate from strong oxidizers, strong acids/bases, and sources of ignition; avoid cross-contamination between wells/plates.
• First aid (general):
  • Skin/eye contact: rinse with water for at least 15 minutes; remove contaminated clothing.
  • Inhalation: move to fresh air; seek medical attention for persistent symptoms.
  • Ingestion: rinse mouth; do not induce vomiting; seek medical attention.
• Waste: collect assay residues and rinsates as organic chemical waste per institutional and local regulations.

Always consult the SDS and product documentation specific to SKU Lib412051 for definitive hazard and response information.

Solvent Selection

For a compound library, solvent choice is application- and assay-dependent rather than library-specific.

• Item-specific solvent details: Not specified for this item; refer to CoA/Spec Sheet.

General guidance for CNS-focused libraries (not item-specific):

• Stock solutions:
  • DMSO is the prevalent vehicle due to broad solubilization capacity; keep final assay DMSO ≤0.1–1% v/v to minimize biological confounds.
  • For poorly soluble chemotypes, co-solvent strategies (DMSO + PEG400 or DMSO + ethanol) or cyclodextrin inclusion can be considered; validate assay tolerance.
• Aqueous buffers:
  • Use physiological pH (7.2–7.4) buffers for cell-based assays. Add 0.01–0.05% nonionic surfactant (e.g., Pluronic F-68, Tween-20) as needed to suppress aggregation (assay-dependent; verify compatibility).
• Volatile organic solvents for intermediate handling:
  • Acetonitrile or methanol for analytical sample prep; ensure complete removal before biological assays if not tolerated.

Comparison (general considerations):

• DMSO: high solvency, hygroscopic; potential cytotoxicity above ~1%.
• DMF/NMP: strong solvents but often less biocompatible; typically avoided in live-cell assays.
• EtOH/MeOH: compatible at low percentages but limited solvency for hydrophobic scaffolds.

Always pilot-test solvent tolerance in your specific assay system; consult the library documentation for any supplier-recommended vehicles.

Storage and Reconstitution

• Item-specific storage (from Product Data):
  • Storage Conditions: Room temperature
  • Shipped In: Not specified for this item; refer to CoA/Spec Sheet.

General guidance for library handling (not item-specific and not overriding the above):

• If supplied as DMSO solutions: store in tightly sealed, inert gas–blanketed plates or vials to limit water uptake; minimize light exposure for photosensitive chemotypes; track freeze–thaw cycles and avoid more than 2–3 where possible.
• If supplied as dry films/solids: reconstitute with anhydrous solvent (commonly DMSO) to the specified stock concentration; vortex and sonicate if needed; verify complete dissolution visually and by analytical spot-check.
• Plate care: equilibrate to room temperature before opening; centrifuge briefly to collect condensate; reseal with low-evaporation seals after dispensing.
• Stability checks: periodically inspect for precipitation, color change, or peak decomposition by LC–MS on representative wells.

Because exact format, solvent, and concentrations are Not specified for this item; refer to CoA/Spec Sheet for definitive reconstitution instructions and long-term storage recommendations specific to SKU Lib412051.

Structure and Identity

This product is a curated screening set of small molecules selected for properties associated with central nervous system (CNS) penetration. As a library, it does not have a single structure or identifier.

• Item-specific identifiers:
  • Molecular formula: Not applicable to a multi-compound library
  • Molecular weight: Not applicable to a multi-compound library
  • CAS, InChIKey, SMILES: Not applicable (set of diverse structures)
• Product Data (item-specific):
  • SKU: Lib412051
  • Product Name: CNS-Penetrant Compound Library
  • Storage Conditions: Room temperature
  • Research Use Note: For research use only
• Composition overview (general/literature guidance, not item-specific):
  • Typical CNS-directed libraries enrich for scaffolds with balanced lipophilicity, limited H-bonding, and compact polar surface area to favor blood–brain barrier (BBB) crossing.
  • Common functional groups include N-heteroaromatics, anilides, carbamates, ureas, small amides, ethers, and halogenated aromatics with constrained polarity.
  • 2D structural features often emphasize 5–6 membered aromatic/heteroaromatic cores with one or two heteroatoms and minimal rotatable bonds.
• Physicochemical windows often targeted (literature, indicative only):
  • MW typically 250–450 Da, cLogP ~2–4, TPSA ≤60–90 Ų, HBD ≤1, HBA ≤7, pKa adjusted to reduce permanent charge at physiological pH.

Note: Specific constituents, identifiers, and plate maps for this SKU are Not specified for this item; refer to CoA/Spec Sheet.

Synthetic Utility

Not directly applicable. The product is a collection of finished small molecules for screening, not a single synthetic building block or reagent.

General notes for chemists advancing hits (literature guidance):

• Retrosynthetic leverage: CNS-like scaffolds frequently contain synthetically tractable motifs (e.g., substituted pyridines, indazoles, anilides) amenable to rapid diversification via cross-coupling (Suzuki, Buchwald–Hartwig), heterocycle formation, and late-stage functionalization.
• Property-driven design: adjust cLogP, pKa, TPSA, and aromatic substitution to manage BBB penetration and efflux; reduce HBDs and rotatable bonds to improve MPO scores.
• De-risking liabilities: avoid structural alerts (anilides vulnerable to metabolism, Michael acceptors, redox cyclers). Use matched molecular pair analysis to tune solubility and clearance.

These considerations apply after hit identification; they are not characteristics of the library as supplied.

Target Specificity

• Item-specific data:
  • Target(s), pathway coverage, or selectivity annotations: Not specified for this item; refer to CoA/Spec Sheet.

Context (general, not item-specific):

• CNS-focused libraries may include chemotypes historically enriched for CNS targets (e.g., GPCR ligands, CNS ion channel modulators). However, without the detailed compound list, no claims can be made about coverage or selectivity for this SKU.

Users should examine the provided compound list (if supplied) to map target classes, remove known frequent hitters, and ensure alignment with the biological objectives of their screen.