PfPKG-IN-1 , CAS No.2866493-89-0

CAS: 2866493-89-0 Cat. No.: P1421101 Formule: C₂₄H₂₂ClN₇OS Poids moléculaire: 492.00

Storage

Store at -20°C

Shipped In

Ice chest + Ice pads

Vue d’ensemble

PfPKG-IN-1 is a imidazole-based inhibitor of Plasmodium falciparum cGMP-dependent protein kinase (PfPKG).

Spécifications

Conditions de stockage de stockage

Store at -20°C

Expédié en

Ice chest + Ice pads

Ce produit nécessite l'expédition en chaîne froide. Les services terrestres et autres services économiques ne sont pas disponibles.

Type d'action

INHIBITOR

Noms et identifiants

Poids moléculaire

492.00

Application Protocols

• Item-specific (Product Data)
  • No validated protocols or recommended dilutions are provided for this item.
• General protocols for small-molecule inhibitors in biochemical assays (non-item-specific)
  1. Stock preparation
     • Warm vial to room temperature in a desiccator. Prepare a 10–50 mM stock in anhydrous DMSO. Vortex and, if needed, brief sonication. Record exact concentration and lot.
  2. Serial dilutions
     • Prepare intermediate DMSO dilutions to minimize aqueous precipitation. Aim for final assay DMSO ≤0.1–1% v/v. Use low-bind tips/tubes.
  3. Enzyme IC50 assay
     • Incubate enzyme with inhibitor for a defined pre-incubation time (e.g., 5–30 min). Initiate with ATP/substrate. Measure activity via radiometric, ADP/ATP-coupled, or fluorescence/luminescence readouts. Include vehicle and positive control wells.
  4. Counter-screens
     • Test for detergent sensitivity (0.01% Tween-20), redox interference, and fluorescence quenching/inner-filter effects as appropriate.
  5. Data analysis
     • Fit concentration–response curves with a 4-parameter logistic model; report IC50 with confidence intervals and note assay conditions (ATP, enzyme, time, temperature).
• General protocols for cell-based assays
  • Dose cells/parasites with a dilution series; maintain constant vehicle. Monitor viability/phenotype and include off-target/cytotoxicity controls.
• Documentation
  • Record plate maps, vehicle %, lot/aliquot IDs, and environmental conditions for reproducibility.

Biological Roles

• Item-specific (Product Data)
  • No biological role or target annotation is specified for this item beyond the product name; refer to primary literature and the CoA/Spec Sheet for any supplier-confirmed details.
• Literature/general background (non-clinical)
  • cGMP-dependent protein kinase (PKG) in Plasmodium (PfPKG) regulates key signaling events in the parasite life cycle, including egress/invasion processes and gametocyte activation. Modulation of PfPKG activity is a common strategy in malaria-focused chemical biology.
  • Small-molecule PfPKG inhibitors are used as chemical probes to interrogate cGMP signaling, dissect stage-specific pathways, and validate target engagement through biochemical and phenotypic assays.
  • Selectivity is an important consideration: cross-reactivity with mammalian kinases (e.g., PKG/PKA) can confound interpretation; orthogonal assays and counterscreens help establish on-target effects.
  • Typical experimental endpoints include enzyme IC50 determination, kinetics (competitive vs non-competitive behavior), cellular EC50 in parasite growth or egress assays, and rescue/epistasis experiments to link phenotype to target modulation.
• Caution
  • Results can depend strongly on assay format, protein construct, ATP concentration, and parasite stage; comparisons across studies should account for these variables.
  • This product is for research use only and not intended for diagnostic, therapeutic, or in vivo clinical applications.

Buffer Applications

• Applicability
  • This product is not a buffer component. It does not define a buffering range or capacity and is not typically used to prepare buffer systems.
• Practical note (general)
  • When used in biochemical assays, it is dissolved in a compatible vehicle (commonly DMSO) and diluted into an assay buffer optimized for the target enzyme (e.g., HEPES- or Tris-based buffers with Mg2+/Mn2+ as needed for kinase activity). Maintain consistent pH and ionic strength to avoid confounding kinetic parameters.
  • Include detergents (e.g., 0.01% Tween-20) and carrier protein (e.g., 0.1% BSA) as appropriate to reduce nonspecific adsorption and aggregation artifacts.

Green Alternatives

• Context
  • As a solid screening compound, “green alternatives” mainly concern solvent choices for dissolution and assay preparation rather than substitution of the compound itself.
• Greener solvent considerations (general)
  • Prefer aqueous buffers with minimal DMSO where solubility allows; titrate down to the lowest vehicle percentage that maintains clear solutions.
  • Where organic cosolvent is needed, consider ethanol or propylene glycol derivatives in biocompatible assays, acknowledging reduced solvency versus DMSO.
  • Avoid halogenated solvents for routine handling; reserve for analytical or stability testing only when justified.
• Comparison (general)
  • DMSO: high solvency; environmental/health profile acceptable at small scale but enhances dermal absorption—use PPE.
  • Ethanol: renewable origin possible; lower toxicity; limited solubility for lipophilic scaffolds.
  • Water/buffer: greenest option; may require pH adjustment or cyclodextrin/surfactant aids to achieve solubility.
• Operational green tips
  • Use concentrated master stocks and dispense with acoustic or low-dead-volume systems to minimize solvent waste.
  • Store aliquots to reduce freeze–thaw cycles and compound waste due to degradation.

Pharmaceutical Uses

• Item-specific (Product Data)
  • No pharmacopeial status, excipient role, or formulation guidance is specified for this item; for research use only.
• Research and development context (non-clinical, no therapeutic claims)
  • Functions as a reference or tool compound in early discovery to probe PfPKG-related biology, support target validation, and benchmark assays.
  • Can serve as a positive control in high-throughput screening (HTS) or as part of focused libraries for structure–activity relationship (SAR) exploration.
  • Material may be used as an analytical reference standard for LC-MS method development, stability-indicating assays, and metabolite identification—provided authentic structure and purity documentation are available from the CoA.
• Formulation for assays (general)
  • Prepare concentrated DMSO stocks (e.g., 10–50 mM) and dilute into assay-compatible media; avoid surfactants or excipients that interfere with readouts (fluorescence, luminescence).
  • For longer incubations or storage in plates, test stability under assay conditions (temperature, light exposure) to ensure consistent potency during the assay window.

Physical Properties

• Item-specific (Product Data)
  • Appearance: Not specified for this item; refer to CoA/Spec Sheet.
  • Purity/grade: Not specified for this item; refer to CoA/Spec Sheet.
  • Molecular weight: Not specified for this item; refer to CoA/Spec Sheet.
  • Melting point, boiling point, density, refractive index, UV cutoff, water/peroxide/metal limits: Not specified for this item; refer to CoA/Spec Sheet.
• Literature/general expectations for kinase inhibitors (solid small molecules)
  • Physical state: frequently crystalline or amorphous solids.
  • Solubility: often highly soluble in DMSO; variable in aqueous buffers depending on ionizable groups and pH. For assay work, 10–50 mM DMSO stocks are typical (general practice).
  • LogP/cLogP: kinase-targeted chemotypes often fall in cLogP ~1.5–4.5 (literature, varies by scaffold).
  • pKa: heteroaromatic amines, sulfonamides, or lactams may impart one or more pKa values; actual values are structure-dependent (not specified for this item).
  • Hygroscopicity/photolability: varies by scaffold; protect from moisture and light as a conservative practice for screening compounds.
• Practical notes
  • Pre-screen solubility in intended assay buffer with final DMSO ≤1–2% v/v to avoid vehicle effects.
  • Use analytical HPLC/UPLC to confirm a single dominant peak prior to dose–response testing; add LC-MS for identity confirmation if structural data become available.

Quality and Grades

• Item-specific (Product Data)
  • Grade/purity: Not specified for this item; refer to CoA/Spec Sheet.
• How to interpret quality for screening compounds (general guidance)
  • Purity: for biochemical/phenotypic screening, ≥95% area by HPLC/UPLC is commonly targeted; confirm by orthogonal methods (NMR, LC-MS) when feasible.
  • Identity: verify via supplier-provided structure identifiers (SMILES/InChI, MW) and cross-check with LC-MS exact mass if available.
  • Residual solvents/inorganics: review CoA for residual solvent profiles and inorganic residues; these can confound cell-based assays at low micromolar doses.
  • Stabilizers: not specified for this item. If stabilizers are present in other products, note potential UV/fluorescence interference.
  • Documentation: retain batch-specific CoA and SDS in ELN; record lot numbers in all assay reports for reproducibility.
• Practical QA tips
  • Run an incoming QC: analytical HPLC purity check, LC-MS for mass, and a quick stability test (e.g., 24–48 h in assay buffer at room temperature) to flag rapid degradation.
  • For SAR projects, ensure plate maps encode lot/aliquot IDs to correlate anomalies with material provenance.

Reaction and Applications

• Applicability to synthetic reactions
  • This product is a research screening compound and is not typically employed as a reagent or solvent in synthetic transformations. No manufacturer reaction applications are provided for this item.
• Relevant applications (general, non-clinical)
  • Chemical biology: use as a reference inhibitor in enzyme assays targeting cGMP-dependent protein kinase from Plasmodium spp. to benchmark assay performance and validate target dependence.
  • Phenotypic screening: evaluate concentration–response in parasite or surrogate models to explore pathway engagement, with appropriate controls for off-target and cytotoxic effects.
  • Mechanistic studies: time-dependent inhibition and reversibility experiments, competition with ATP or substrate, and assessment of selectivity across related kinases (e.g., mammalian PKG/PKA) where data are available in literature.
• Practical notes
  • Confirm compound integrity before use (HPLC/LC-MS) and re-check after prolonged incubations in assay buffer.
  • Implement counter-screens (e.g., detergent-sensitive aggregation tests, redox activity assays) to rule out assay interference.
  • Maintain consistent vehicle content across wells/plates and include vehicle controls to quantify baseline effects.

Reaction Conditions

• Not typically applicable
  • No manufacturer-provided reaction conditions apply to this item because it is not used as a reagent in chemical synthesis.
• Assay conditions (general, for context rather than synthesis)
  • Enzyme assays: buffer such as 25–50 mM HEPES, pH 7.0–7.5, with appropriate divalent cations (e.g., Mg2+) and ATP near Km to assess competitive behavior; temperature often 25–37 °C. Maintain constant DMSO across wells (≤0.1–1% v/v).
  • Cell/parasite assays: culture-appropriate media with controlled serum and vehicle content; include positive and negative controls; measure dose–response over a log range (e.g., 11-point 3-fold serial dilutions).
  • Stability checks: incubate inhibitor in assay buffer for the assay duration and analyze by HPLC to ensure no significant degradation that could skew potency estimates.
• Labeling
  • The above parameters are general literature practices and are not specifications for this item.

Safety and Handling

• Item-specific (Product Data)
  • GHS classification, pictograms, signal word, H-statements: Not specified for this item; refer to SDS.
  • Storage: Store at −20 °C.
  • Shipping: Ice chest + ice pads.
• General laboratory safety (not item-specific; follow institutional SOPs and SDS)
  • PPE: lab coat, nitrile gloves, safety glasses; use in a chemical fume hood when weighing or preparing stock solutions, especially with DMSO vehicles that enhance dermal absorption.
  • Handling: avoid inhalation/ingestion/skin contact. Prevent cross-contamination between screening plates by preparing master stocks and single-use aliquots.
  • Incompatibilities: strong oxidants and strong acids/bases may degrade many drug-like organics; avoid prolonged exposure to moisture and light.
  • First aid (general): on skin/eye contact, rinse with water for ≥15 minutes and remove contaminated clothing; if inhaled, move to fresh air; if ingested, seek medical attention. Always defer to SDS for authoritative instructions.
  • Waste: collect solutions and contaminated disposables as halogenated or non-halogenated organic waste per local regulations; segregate DMSO-containing waste if required.
  • Special risks: potency toward biological targets implies activity at low concentrations; minimize aerosol formation and wipe spills promptly with inert absorbent.

Solvent Selection

• Item-specific (Product Data)
  • No solvent recommendations are specified for this item; refer to CoA/Spec Sheet.
• General guidance for small-molecule kinase inhibitors used in screening
  • Primary stock solvent: DMSO is the de facto choice due to broad solubilizing power for heteroaromatic, moderately lipophilic compounds. Typical stock: 10–50 mM (general practice).
  • Cosolvents for aqueous work: prepare working solutions by serial dilution into assay buffer, maintaining final DMSO ≤0.1–1% v/v to limit vehicle effects on enzymes or cells.
  • Alternative solvents: DMF or acetonitrile may help dissolve recalcitrant solids but are less favored for routine bioassays; ethanol can be acceptable in some cell assays at ≤0.1–0.5% v/v.
  • Buffer additives: low levels of non-ionic surfactants (e.g., 0.01% Tween-20) can mitigate aggregation artifacts; confirm they do not perturb the assay readout.
• Comparison (general)
  • DMSO: highest solvency, strong skin permeation, hygroscopic; most assay-compatible at low %.
  • Acetonitrile: volatile, good solvency, may affect enzyme activity; use cautiously.
  • Ethanol: biocompatible at low %, limited solvency for more lipophilic scaffolds.
• Practical tips
  • Warm to room temperature and vortex/sonicate to aid dissolution; avoid heating above 40 °C unless stability is documented.
  • Filter 0.2 µm if particulate persists; verify no adsorption losses to filters at low micromolar levels.

Storage and Reconstitution

• Item-specific (Product Data)
  • Storage conditions: Store at −20 °C.
  • Shipping: Ice chest + ice pads.
• General guidance (not item-specific)
  • Upon receipt: allow the sealed container to equilibrate to room temperature before opening to minimize condensation. Open in a low-humidity environment.
  • Aliquoting: prepare single-use aliquots of concentrated DMSO stock (e.g., 10–50 mM) to avoid repeated freeze–thaw; store aliquots at −20 °C or −80 °C in tightly sealed, inert vials.
  • Protection: store desiccated and protected from light. Use amber vials or foil wrap if chromophore sensitivity is suspected.
  • Stability checks: periodically verify integrity by analytical HPLC/LC-MS, especially after >6 months storage or multiple thaw cycles.
  • Thawing: thaw aliquots at room temperature, mix gently, and promptly return unused material to cold storage. Avoid repeated freeze–thaw of the bulk solid and of DMSO stocks.
  • Aqueous working solutions: prepare fresh on the day of use; filter if needed (0.2 µm) and discard after the experiment to avoid degradation or adsorption losses.
• Disclaimer
  • Where specific stability data (shelf-life, light/moisture sensitivity) are required, consult the item’s CoA/Spec Sheet and SDS; these supersede general guidance.

Structure and Identity

• Item-specific (Product Data)
  • Product name: PfPKG-IN-1 (SKU: P1421101)
  • CAS: 2866493-89-0
  • 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.
• Literature/general description
  • “PfPKG-IN-1” commonly denotes a small-molecule inhibitor used as a chemical probe against cGMP-dependent protein kinase from Plasmodium spp. (PfPKG). Specific structure, substituent pattern, and stereochemistry vary by supplier and publication.
  • Without a supplier-verified structure, detailed functional group analysis and 2D structural description cannot be provided for this catalog item.
  • Recommendation: consult the item’s Certificate of Analysis (CoA) and Structure/Spec Sheet for definitive identifiers (SMILES, InChI, MF, MW) prior to method development, LC-MS tracking, or registration in ELN/SDMS.

Synthetic Utility

• Applicability
  • This product is a bioactive small molecule supplied for screening/assay use and is not typically employed as a synthetic reagent, catalyst, or building block. No synthetic utility is claimed in the product data.
• General note
  • If structural information becomes available and derivatization is desired for probe development (e.g., biotinylation, photoaffinity tags, fluorophore conjugation), conduct feasibility analysis to identify modifiable positions that retain PfPKG engagement; this requires SAR data and is outside the scope of this listing.
  • For analytical derivatization (e.g., forming salts to enhance LC or improve crystallinity), consult stability and pKa information once structure is confirmed.

Target Specificity

• Item-specific (Product Data)
  • No target specificity, antigen/epitope information, or species reactivity is provided for this item. This section typically applies to biologics/antibodies; for small molecules, consult literature and the CoA for any target annotations.
• Note
  • The product name suggests an association with PfPKG in common research usage, but target identity, potency, and selectivity are not specified for this catalog item and should not be inferred. Verify using supplier documentation and independent assays.