Pimicotinib - ≥99% , CAS No.2253123-16-7

CAS: 2253123-16-7 Cat. No.: P1450751 Formula: C₂₂H₂₄N₆O₃ Molecular Weight: 420.46

GRADE & PURITY ≥99%

Storage

Store at 2-8°C

Shipped In

Wet ice

Overview

Pimicotinib is a CSF1R inhibitor with antitumor activity.

Specifications

Specifications & Purity

≥99%

Storage

Store at 2-8°C

Shipped In

Wet ice

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

Action Type

INHIBITOR

Purity

≥99%

Names and Identifiers

Molecular Weight

420.46

Application Protocols

Supplier-verified, tested application protocols and recommended conditions are not specified for this item; refer to the CoA/Spec Sheet.

General example workflows (for guidance only; not item-specific specifications):

• Biochemical kinase inhibition assay: prepare serial dilutions in assay buffer with constant DMSO (e.g., 0.1% v/v); incubate with recombinant CSF1R kinase domain and ATP at Km; measure ADP formation or peptide phosphorylation (TR-FRET, ADP-Glo, or LC–MS readouts). Fit IC50/kinetics with appropriate models.
• Cell-based phospho-signaling assay: pre-stimulate CSF1R-expressing cells with CSF1; treat with compound for 30–60 min; quantify p-CSF1R or downstream p-ERK/p-AKT by Western blot/ELISA. Include vehicle and pathway controls.
• Stability check: incubate working solutions at room temperature and 37 °C; sample at intervals for LC–MS to ensure concentration integrity during assay windows.

Always validate conditions in your laboratory and consult the SDS and CoA before use.

Biological Roles

General/literature context (not item-specific claims):

• Pimicotinib is described in the literature as a potent, selective inhibitor of the receptor tyrosine kinase CSF1R (c-FMS), a key regulator of mononuclear phagocyte lineage biology. CSF1R is activated by CSF1 (M-CSF) and IL-34, driving macrophage survival, proliferation, and differentiation.
• Inhibition of CSF1R enables interrogation of macrophage-dependent signaling, including downstream PI3K/AKT, ERK/MAPK, and JAK/STAT cascades, and can modulate gene programs associated with inflammation, osteoclastogenesis, and tissue remodeling.
• As a chemical probe, pimicotinib can be used to study receptor autophosphorylation, receptor internalization/turnover, and cross-talk with other receptor tyrosine kinases in cell systems expressing CSF1R.
• Selectivity over kinome panels is central for interpretation; literature sources report high selectivity of modern CSF1R inhibitors, but users should confirm selectivity data under their assay conditions (biochemical vs cellular potency, ATP competition, and time-dependence).

Practical usage notes:

• Employ appropriate controls (inactive analogs, unrelated kinase inhibitors) to differentiate on-target from off-target effects.
• For macrophage-related assays, pre-condition cells with CSF1 or IL-34 to elicit robust pathway activation before inhibitor treatment; quantify effects via phospho-CSF1R ELISA/Western, transcriptional profiling, or functional readouts (e.g., macrophage viability assays).

Buffer Applications

This item is a hydrophobic small-molecule research probe rather than a buffering agent. It is not typically used to prepare buffer systems.

Practical notes (general):

• When dosing into aqueous buffers (e.g., PBS, HBSS, assay media), prepare concentrated DMSO stocks and perform controlled dilutions to a constant final DMSO percentage across all conditions (commonly 0.05–0.5% v/v).
• If the compound includes ionizable groups (verify via CoA/structure), pH of the receiving buffer may influence solubility and apparent potency; perform pH-controlled assays or include pH-matched vehicle controls.

Green Alternatives

Because this compound is used as a research probe/standard rather than as a process solvent or bulk reagent, “green alternatives” primarily relate to solvent choices for preparation and dilution.

• Greener solvent considerations (general):
  • Prefer ethanol or water-containing systems where solubility and assay tolerance permit. Ethanol has a better EHS profile than DMF/NMP and lower persistence than DMSO, though solvency is typically lower.
  • 2-MeTHF and CPME are not generally relevant for aqueous biological assays but can be considered for non-aqueous analytical preparations if compatible with the method.
  • Reduce DMSO usage by preparing minimal-volume, high-concentration stocks and performing serial dilutions just-in-time.

Comparison (general, qualitative):

• DMSO: excellent solvency; low volatility; widely accepted in bioassays; environmental persistence is moderate; generally preferred baseline.
• Ethanol: greener, readily biodegradable; lower cytotoxicity at low % v/v; may have insufficient solvency for hydrophobic scaffolds.
• Propylene glycol/glycerol: benign but viscous; limited solvency for many kinase inhibitors; may interfere with some assays.

Operational green tips:

• Minimize waste by aliquoting stocks to match study size; avoid over-preparation.
• Use micro-scale assays (384/1536-well formats) to reduce solvent consumption.
• Segregate halogenated vs non-halogenated waste streams to facilitate compliant disposal.

Pharmaceutical Uses

No clinical/therapeutic claims are made. For research use only.

General formulation/analytical contexts (not item-specific specifications):

• Can serve as a reference standard or system suitability compound for development of LC–MS/MS bioanalytical methods targeting CSF1R inhibitors in preclinical matrices.
• Useful for preformulation studies in discovery settings (solubility screening across pH/cosolvent systems, stability in simulated gastric/intestinal fluids, or plasma stability), with all results to be confirmed experimentally for pimicotinib specifically.
• In medicinal chemistry workflows, may be used as a benchmark control in CSF1R-focused SAR campaigns to normalize potency shifts across series.
• If salt forms or solid-state variants exist, document and standardize the form used in any comparative studies; dose on free-base/free-acid equivalents as applicable.

Compliance note:

• Any use in GMP, GLP, or regulated assays requires obtaining the lot-specific CoA, impurity profile, and stability data. This catalog entry provides storage conditions (2–8 °C; shipped on wet ice); other pharmacopeial attributes are not specified for this item.

Physical Properties

Item-specific properties (this catalog entry):

• Appearance: Not specified for this item; refer to CoA/Spec Sheet.
• Melting point, boiling point, density, refractive index, pKa, logP/logD, solubility: Not specified for this item; refer to CoA/Spec Sheet.

General/literature guidance (not item specifications):

• Many kinase inhibitors of this class are crystalline solids with limited aqueous solubility at neutral pH and are typically prepared as DMSO stock solutions (e.g., 10–50 mM) for cell-based screening. Actual solubility and polymorph behavior can vary; verify experimentally.
• Hygroscopicity: small-molecule inhibitors are usually non-hygroscopic but can exhibit slow moisture uptake depending on salt form and crystallinity; handle quickly to minimize exposure if working on microgram scales.
• Ionization: reported CSF1R inhibitors often contain weakly basic nitrogens (pKa typically 4–9, literature range for related scaffolds), which can affect solubility across pH; determine the exact pKa for pimicotinib from analytical measurements or authoritative databases before constructing buffers or dosing solutions.

Practical tips:

• Determine solubility in intended assay media (e.g., HBSS, PBS + % FBS) with DMSO cosolvent titration; monitor for precipitation upon dilution.
• If crystallinity complicates dissolution, gentle warming (≤40 °C) and vortex/sonication can aid dissolution, followed by filtration (0.2 µm PTFE).

Quality & Grades

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

How to interpret grades (general guidance):

• Research-grade screening compounds are typically provided at high chemical purity (often ≥95% by HPLC/LC-MS) with accompanying analytical data (chromatogram, MS, sometimes NMR). Low levels of residual solvents and counter-ions may be present depending on the manufacturing route and salt form. Always review the lot-specific CoA for assay/purity method, reference standard, and acceptance criteria.
• If UV-based analytics are planned (e.g., HPLC-UV quantification), check the UV spectrum for absorption maxima and potential baseline drift; high-purity materials reduce background and facilitate quantitation.
• If the product contains a defined salt form, hydrate, or solvate, the CoA will indicate it; this can influence potency on a mass basis—calculate doses on a free-base/free-acid equivalent when required.

What is specific to this item:

• Storage is defined: Store at 2–8 °C; shipped on wet ice. No stabilizers or special additives are indicated in the listing. All other specifications must be confirmed from the lot CoA/Spec Sheet before use in screening or method development.

Reaction & Applications

This product is a finished bioactive small molecule intended primarily for screening, target validation, and mechanism studies rather than as a synthetic reagent.

Research applications (general, literature-based; not item-specific claims):

• Chemical biology probe: Pimicotinib is reported in the literature as a selective CSF1R kinase inhibitor and is used to interrogate CSF1/IL-34–CSF1R signaling pathways in macrophages and osteoclasts, enabling studies of receptor phosphorylation, downstream PI3K/AKT and MAPK pathways, and transcriptional responses.
• Assay development: suitable as a positive control/reference compound in biochemical kinase assays (enzyme inhibition kinetics, IC50 determination) and in cell-based phospho-signaling readouts (e.g., p-CSF1R, p-ERK by Western blot).
• Target engagement: supports CETSA, NanoBRET/kinase tracer displacement, or chemoproteomics workflows to confirm cellular binding in relevant models.

Practical tips:

• Prepare concentrated DMSO stocks and avoid freeze–thaw cycling; aliquot for consistency across screening runs.
• Confirm identity and purity via LC–MS prior to critical assays. Establish a stability-indicating LC method to monitor potential degradation in storage solvents.
• Use a defined dilution protocol to control final DMSO content across dose–response curves. Include vehicle controls and orthogonal readouts to exclude assay interference.

Reaction Conditions

Not typically applicable. Pimicotinib is supplied as a finished research compound rather than a reagent or catalyst for chemical synthesis.

General practical conditions for handling in assays and analytics (not item-specific specifications):

• Stock preparation: dissolve in anhydrous DMSO to 10–50 mM; vortex/sonicate gently. Filter if necessary (0.2 µm PTFE). Record exact concentration by weight and adjust for purity if known from CoA.
• Storage of solutions: keep light-protected aliquots at ≤–20 °C for long-term storage where compatible; avoid repeated freeze–thaw cycles.
• Assay dosing: dilute into pre-warmed media/buffer to final DMSO 0.05–0.5% v/v. Equilibrate 15–30 min to ensure complete mixing before readout.
• LC–MS analysis: use water/acetonitrile (0.1% formic acid) or water/methanol mobile phases; start with a 5–95% organic gradient over 10–15 min on C18; adjust as needed. Optimize source parameters for positive ESI if basic sites are present.

For any synthetic transformations involving the scaffold (custom chemistry), consult the primary structure and published procedures; no reaction condition data are specified for this item.

Safety & Handling

Item-specific hazard data for this SKU:

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

General laboratory safety guidance (not a substitute for the SDS):

• Handle in a chemical fume hood; avoid inhalation of dust/aerosols and skin/eye contact. Wear appropriate PPE: lab coat, safety glasses, and chemical-resistant gloves (e.g., nitrile). For weighing fine powders, consider double-gloving and antistatic measures to reduce airborne particulates.
• Avoid contact with strong oxidizers and strong acids/bases unless stability has been confirmed. Use dedicated, clean tools for microgram-to-milligram quantities to prevent cross-contamination in screening campaigns.
• First aid (overview; consult SDS): on skin/eye contact, rinse with water for at least 15 minutes; remove contaminated clothing. If inhaled, move to fresh air. If ingested, rinse mouth; do not induce vomiting; seek medical attention.
• Waste disposal: collect solutions/solids in suitable organic waste containers; dispose per institutional and local regulations.
• Special risks: none are specified for this item. As with many bioactive small molecules, minimize exposure and environmental release. Always defer to the product SDS for authoritative guidance.

Solvent Selection

Item-specific solubility is not provided; verify empirically. The following is general guidance for hydrophobic kinase inhibitors used in screening.

• Primary stock solvent choices (general):
  • DMSO: preferred for making concentrated stocks (e.g., 10–50 mM) due to broad solvency and assay compatibility at ≤0.1–0.5% v/v.
  • DMF or NMP: alternatives when DMSO solubility is inadequate; assess cytotoxicity for biological assays.
  • Aqueous buffers: often require co-solvent (DMSO, ethanol) or pH adjustment if ionizable groups are present.
• Polarity/miscibility (general): DMSO and DMF are fully miscible with water and many organics; they facilitate serial dilutions into media. Ethanol can be used for less water-tolerant systems, but may affect cells at >0.5–1% v/v.
• Practical tips:
  • Establish a solvent hierarchy: attempt DMSO first; if precipitation occurs on aqueous dilution, increase incubation time, warm gently, or include surfactant (e.g., 0.01–0.05% Tween-80) where appropriate to the assay.
  • Filter final assay solutions through 0.2 µm PTFE or PES to remove particulates.
  • For analytical quantitation (LC–MS), use LC–MS grade solvents; consider adding 0.1% formic acid or 5 mM ammonium formate for positive-mode ionization, as method-appropriate.
• Compare alternatives:
  • DMSO (benchmark) vs 2-pyrrolidone (stronger solvency, higher viscosity) vs ethanol (greener but lower solvency). Select based on assay tolerance and solubility needs.

Storage & Reconstitution

Item-specific instructions (from Product Data):

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

Additional guidance (general; not item-specific specifications):

• Solid storage: keep container tightly closed, desiccated, and protected from light. Allow vial to equilibrate to room temperature before opening to minimize condensation.
• Reconstitution: dissolve the required amount in anhydrous DMSO to prepare a concentrated stock (e.g., 10–50 mM). Vortex and, if needed, sonicate briefly to aid dissolution. Filter through a 0.2 µm PTFE syringe filter to remove particulates.
• Aliquoting: dispense single-use aliquots into inert, light-protective microvials; purge headspace with inert gas if prolonged storage is anticipated.
• Solution storage: for longer-term stability, store aliquots at –20 to –80 °C; avoid repeated freeze–thaw cycles. Track freeze–thaw count and discard aliquots showing precipitation or degradation by LC–MS/HPLC.
• Compatibility: verify solubility and stability in the intended assay buffer/media prior to large experiments. Maintain a constant final DMSO percentage across all treatment conditions.

Note: If the product is supplied as a particular salt/hydrate/solvate, or with stabilizers, refer to the lot-specific CoA for exact handling and mass-correction details.

Structure & Identity

• Item-specific identifiers provided: CAS 2253123-16-7; Product name: Pimicotinib; SKU: P1450751.
• 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 (non-item-specific):

• Pimicotinib is a small-molecule kinase inhibitor reported in the literature as a selective CSF1R (colony-stimulating factor 1 receptor) inhibitor used as a chemical probe for macrophage/osteoclast signaling studies. Exact stereochemistry and substituent pattern should be verified from primary references or the product CoA before use in regulated work.
• Structural features (literature, descriptive): typical CSF1R inhibitors are heteroaromatic, H-bond acceptor–rich scaffolds designed to engage the ATP-binding site; confirm the precise ring system and functional groups from the CoA/structure file for this lot.

Notes for users:

• For publication or registration, obtain the definitive structure file (SDF/MOL, exact SMILES, InChIKey) from the CoA/Spec Sheet associated with this SKU/lot.

Synthetic Utility

This product is a final bioactive small molecule and is not typically used as a synthetic building block or reagent.

General considerations for chemists:

• If analog synthesis is pursued, pimicotinib may inform retrosynthetic analysis for related CSF1R inhibitor scaffolds (e.g., fragment linking to hinge-binding motifs, optimization of solvent-exposed vectors). However, the parent compound itself is not commonly incorporated into further transformations.
• For analytical method development, having a stable, well-characterized sample enables preparation of calibration curves, internal standards (if isotopologues are available), and stability-indicating methods to support synthetic campaigns.
• Derivatization for target engagement studies (e.g., photoaffinity or biotinylated probes) might be feasible if a solvent-exposed handle exists on the scaffold; the exact position must be determined from the verified structure and SAR to avoid loss of potency.

Summary:

• Treat pimicotinib as a reference/probe compound. For synthetic chemistry needs, consult primary literature on CSF1R inhibitor series to identify functional handles suitable for late-stage diversification rather than modifying the parent molecule directly.

Target Specificity

No target specificity data are provided in the product data for this SKU. This section typically lists antibody antigens/epitopes or, for bioactive small molecules, confirmed primary targets from the supplier. For this item, refer to the CoA/Spec Sheet for any supplier-verified target information.

Note: Literature sources describe pimicotinib as a selective CSF1R inhibitor; however, such information is not supplier-verified here and should not be treated as item-specific without consulting the CoA.