Namitecan - 10mM in DMSO , CAS No.372105-27-6

CAS: 372105-27-6 Cat. No.: N655466 Formula: C₂₃H₂₂N₄O₅ Peso molecolare: 434.44 PubChem CID: 10950142

QUALITÀ & PUREZZA 10mM in DMSO

Storage

Store at -80°C

Shipped In

Dry ice packs + Cold packs

Panoramica

Namitecan is a potent topoisomerase I inhibitor, with antitumor property.

In Vitro

Namitecan and cetuximab cooperate in inhibiting EGFR expression. Namitecan induces a dose-dependent decrease in EGFR expression in the different cell lines. ST1968 induces a comparable level of apoptosis in A431 and A431/TPT cells with IC 50 of 0.21 and 0.29 μM. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

In Vivo

Namitecan (10 mg/kg) in combination with cetuximab (1 mg/mouse) induces synergistic antitumor effects in SCC models as a function of EGFR gene copy number . ST1968 (25 mg/kg) causes acceptable body weight loss and no toxic deaths. ST1968 produces a 100% complete response rate in the mice bearing the A431 tumor, and retains a relevant activity in the topotecan-resistant tumor. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

IC50& Target:Topoisomerase I

Specifiche

Specifiche e purezza

10mM in DMSO

Meccanismi biochimici e fisiologici

Namitecan is a potent topoisomerase I inhibitor, with antitumor property.

Condizioni di conservazione di stoccaggio

Store at -80°C

Spedito in

Dry ice packs + Cold packs

Questo prodotto richiede spedizione a catena fredda. I servizi di terra e altri servizi economici non sono disponibili.

Tipo di azione

INHIBITOR

Nomi e identificatori

Isomeri SMILES

CC[C@@]1(C2=C(COC1=O)C(=O)N3CC4=C(C5=CC=CC=C5N=C4C3=C2)/C=N/OCCN)O

CAS alternativo

372105-27-6

PubChem CID

10950142

Termini MeSH

namitecan;ST 1968;ST-1968;ST1968

Peso molecolare

434.44

Application Protocols

Tested applications and recommended protocols: Not specified for this item; refer to CoA/Spec Sheet.

General, non-validated guidance (for planning only; verify in-house):

• Cell viability/DDR assays: Prepare 10 mM DMSO stock; perform 8–10 point dose–response (e.g., 0.1 nM to 10 μM). Incubation 24–72 h depending on endpoint; include vehicle control and positive/negative controls as appropriate.
• Mechanistic studies: For short-pulse treatments (e.g., γH2AX, comet assays), expose cells for 0.5–4 h at submicromolar doses, then washout and recover in fresh media.
• Enzyme studies: If using purified human Top1, work in buffers at pH 6.0–7.0 with low ionic strength; include 1–2% DMSO if needed for solubility and preserve lactone by avoiding basic conditions.

These are illustrative class-level suggestions and are not part of the validated product specifications. Users must optimize for their specific models and readouts.

Biological Roles

Item-specific biological roles: Not specified for this item; refer to CoA/Spec Sheet and primary literature.

Literature/class-level context (for camptothecin analogs; not a medical claim):

• Molecular target: Eukaryotic DNA topoisomerase I (Top1). These agents intercalate at the cleavage site and stabilize the covalent Top1–DNA complex, preventing religation.
• Cellular consequences: Accumulation of DNA single-strand breaks that are converted to double-strand breaks upon replication fork collision; activation of DNA damage response (DDR) pathways including ATR/Chk1 and p53-dependent checkpoints; induction of apoptosis or senescence depending on context.
• Selectivity considerations: Activity is S-phase dependent; cells with defects in homologous recombination repair or checkpoint signaling can display heightened sensitivity.
• Resistance mechanisms (general): Upregulation of drug efflux transporters (e.g., ABCG2), Top1 mutations or downregulation, enhanced DNA repair capacity, and altered intracellular trafficking.

Use in research:

• Tool compound to probe replication stress, checkpoint integrity, and synthetic lethality interactions in cell lines and organoids.
• Benchmark control in screening panels targeting DDR modulators.

Note: All biological information above is provided as general background for the compound class. For Namitecan specifically, consult the primary literature corresponding to CAS 372105-27-6 / CID 10950142 before designing experiments.

Buffer Applications

Not a buffering reagent: Namitecan is not used to prepare pH buffer systems.

Practical formulation notes for assays (general guidance):

• Vehicle: Deliver from DMSO stocks; keep final DMSO ≤0.1–0.5% v/v in cell culture where possible, with matched vehicle controls.
• Aqueous media: If higher apparent solubility is needed, consider acidifying the medium slightly (within biological tolerance) or using acceptable solubilizing excipients (e.g., 0.5–2% hydroxypropyl-β-cyclodextrin) validated for your system.
• Avoid basic buffers (e.g., Tris at high pH) and prolonged incubations at elevated temperatures that can shift the lactone–carboxylate equilibrium toward hydrolysis.

For analytical buffers (LC–MS/HPLC):

• Use volatile acids (0.1% formic acid) in water/ACN to preserve lactone and enhance ionization; minimize buffer strength and pH >7.

All recommendations are general to camptothecin-like compounds and should be validated empirically for Namitecan.

Green Alternatives

Context: For small-molecule tool compounds like Namitecan, the principal environmental impacts arise from solvent selection for stock preparation, purification, and any synthetic steps if performed in-house.

Practical greener choices (general guidance):

• Stock solutions: Prefer DMSO over DMF/NMP when compatible with assays; DMSO has a more favorable toxicological profile and is widely accepted in bioassays.
• Aqueous vehicles: Consider cyclodextrin-based solubilizers or micellar media to reduce organic solvent content during dosing, if they do not perturb the biology under study.
• Workup/extraction (if synthesizing/derivatizing): Replace chlorinated solvents (DCM/CHCl3) with ethyl acetate or 2-MeTHF where feasible; evaluate CPME or 2-MeTHF as greener ethers with lower peroxide tendencies than THF and better safety than diethyl ether.
• Purification: Employ reversed-phase preparative HPLC using water–acetonitrile (ACN) with formic acid rather than normal-phase systems using large volumes of hexanes/DCM, when compatible.

Comparison (general, qualitative):

• DMSO vs DMF/NMP: DMSO—lower worker exposure concerns and better biodegradability; DMF/NMP—reproductive toxicity concerns and stricter regulatory oversight.
• 2-MeTHF/CPME vs THF/DCM: often lower VOC emissions and improved safety profiles; check solubility/selectivity constraints.

Caveats:

• Verify compound stability in chosen greener media (pH, light, temperature). For lactone-containing scaffolds, avoid basic micellar systems that could accelerate hydrolysis.

Pharmaceutical Uses

Regulatory/compendial status for this catalog item: Not specified for this item; refer to CoA/Spec Sheet. This product is for research use only.

Context (non-clinical; no therapeutic claims):

• Compound class: Camptothecin analogs have been extensively investigated in drug discovery as topoisomerase I poisons. Namitecan has been reported in the research literature within this class. Any evaluation pertains to preclinical research contexts, not approved pharmaceutical use.
• Formulation research (general): Due to poor aqueous solubility and lactone hydrolysis risk, discovery formulations often explore acidic aqueous vehicles, DMSO cosolvent systems, or lipid/cyclodextrin carriers to maintain the active lactone. Salt formation on basic side chains can modulate solubility but may also influence lactone stability—tradeoffs must be empirically assessed.
• Analytical development: Quantification commonly uses LC–MS/MS with dual-analyte tracking (lactone and carboxylate). Stability-indicating methods at biologically relevant temperatures are essential.

Important: This product is not manufactured under GMP, is not an API or excipient, and is not intended for any human or veterinary use. All pharmaceutical context provided is for background information guiding research-only formulation and analytical experiments.

Physical Properties

Item-specific specifications:

• 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, UV cutoff, residual metals/impurities: Not specified for this item; refer to CoA/Spec Sheet.

Literature/general properties for camptothecin-class analogs (not item-specific; verify for Namitecan before use):

• Physical state: typically solid powders, light-sensitive.
• Solubility profile: low aqueous solubility at neutral pH; readily soluble in polar aprotic organic solvents (e.g., DMSO); limited solubility in ethanol/MeOH; solubility often increases in mildly acidic media due to protonation of basic substituents.
• Acid–base behavior: E-ring lactone can hydrolyze to the corresponding carboxylate at basic or high-ionic-strength conditions; the lactone form is favored in acidic environments and organic solvents.
• LogP/logD: camptothecin analogs commonly show moderate-to-high lipophilicity; exact values are structure-dependent and must be confirmed for Namitecan from primary data.

Practical implications (general):

• Prepare concentrated DMSO stocks (e.g., 10–50 mM) and dilute into aqueous media immediately before use to limit lactone hydrolysis.
• Use amber vials or foil wrap; minimize exposure to light and elevated temperatures.
• Pre-warm buffers can accelerate hydrolysis; keep solutions cold when feasible and avoid alkaline pH.

Quality and Grades

Item-specific grade/purity: Not specified for this item; refer to CoA/Spec Sheet.

Interpretation and guidance:

• Research-use only: This product is designated for laboratory research use. It is not an excipient, not GMP-qualified, and not intended for human or veterinary administration.
• Small-molecule library compounds: These are typically supplied at research grade with identity and purity confirmed by appropriate analytical methods (e.g., NMR, LC–MS, HPLC). When the specific assay requirements are stringent (e.g., biochemical kinetics, crystallography), request and review the latest CoA, including analytical chromatograms and water/solvent content if applicable.
• UV/LC suitability: If planning quantitative LC–MS or HPLC assays, consider the need for low-UV-absorbing residuals and provide your method requirements to match lot specifications.
• Stabilizers: Not specified for this item. If stabilizers or salt forms are used, they will be stated on the CoA. For lactone-containing compounds, absence of stabilizers means users should manage pH and temperature during solution handling to preserve the lactone form.

Recommendations:

• Define acceptance criteria (purity thresholds, residual solvents, form) for your application and confirm lot conformance.
• If orthogonal identity confirmation is required (e.g., for screening hits), consider in-house verification by HRMS and 1H/13C NMR upon receipt.

Reaction and Applications

Scope: Namitecan is supplied as a research small molecule; it is not primarily used as a synthetic reagent. Applications are therefore centered on chemical biology and mechanism-of-action studies rather than stoichiometric transformations.

Research applications (literature, class-level):

• Enzymology/Mechanism studies: Camptothecin-class molecules act as topoisomerase I poisons by stabilizing the Top1–DNA cleavage complex (ternary complex), enabling studies of DNA topology, replication stress, and DNA damage signaling pathways.
• Cell-based assays: Used as a tool compound to induce replication-associated DNA breaks for probing cell-cycle checkpoints, DDR pathway dependencies, and synthetic lethality screens. Typical working concentrations range from low nM to low μM, depending on cell line and endpoint; users must empirically optimize.
• Biophysical/structural biology: Serve as ligands in binding assays (SPR, ITC, DSF) with purified Top1 or surrogate constructs to map binding energetics; lactone integrity may influence affinity.
• Analytical method development: A useful analyte for developing LC–MS methods for lactone/carboxylate interconversion monitoring as a function of pH and matrix.

Notes specific to handling (general):

• Maintain acidic or neutral conditions and minimize time in aqueous media before assays to preserve the lactone.
• Control DMSO content in biological assays to ≤0.1–0.5% v/v; include vehicle controls.

Manufacturer Applications: Not provided; users should align use with their internal assay SOPs and research goals.

Reaction Conditions

As supplied, Namitecan is a research tool compound rather than a reagent; no synthetic reaction conditions are specified for this item.

General handling and solution preparation conditions (guidance for assays and analytics; not item-specific):

• Stock preparation: dissolve in anhydrous DMSO to prepare 10–50 mM master stocks; sonication or gentle warming (≤40°C) may help dissolution. Filter through 0.2 μm PTFE if particulate persists.
• Working solutions: dilute into pre-equilibrated media or buffers immediately before use; maintain final DMSO at assay-tolerable levels (often ≤0.1–0.5% v/v for cells).
• pH and stability: avoid pH >7.4 where feasible to limit lactone hydrolysis; short exposures at neutral pH are typically acceptable for dosing protocols.
• Light/temperature: protect from light (amber vials, foil wrap) and keep on ice during extended setup. Do not leave aqueous solutions at room temperature for prolonged periods.
• Analytical conditions: LC–MS with water/ACN + 0.1% formic acid; column temps 30–40°C; monitor both lactone and carboxylate peaks to ensure stability assessment.

Note: These conditions are general to camptothecin-like compounds and should be validated experimentally for Namitecan. For any synthetic transformations on this molecule, consult primary literature for CAS 372105-27-6 and adapt conditions accordingly.

Safety and Handling

Authoritative source: Always consult the SDS for SKU N655466 for definitive and current hazard information.

Item-specific hazard data provided:

• 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.

General safety considerations for camptothecin-class research compounds (literature; not item-specific):

• Potential hazards: may be acutely toxic, cytotoxic, mutagenic, or reproductive toxins. Avoid inhalation, ingestion, and skin contact. Handle as a potent bioactive with containment.
• Engineering controls: work in a certified chemical fume hood or ventilated enclosure; consider closed-transfer systems for weighing/aliquoting.
• PPE: lab coat, safety glasses, double nitrile gloves; consider chemo-rated gloves if frequent handling; use dedicated tools to avoid cross-contamination.
• Hygiene: avoid creating dust/aerosols; clean benches with appropriate decontamination agents; segregate waste in clearly labeled containers.
• Incompatibilities: avoid strong bases (can promote lactone hydrolysis), strong oxidizers, and prolonged exposure to light/heat.
• First aid (overview): in case of skin contact, wash with plenty of water and soap; for eye contact, rinse cautiously for several minutes; if inhaled, move to fresh air; if ingested or in case of exposure concerns, seek medical attention. Provide SDS to responders.

Environmental handling: collect all solutions, wipes, and disposables as hazardous chemical waste; do not discharge to drains.

Solvent Selection

Applicability: As a hydrophobic small molecule, Namitecan is typically handled as concentrated stocks in aprotic polar solvents.

General guidance (class-level, not item-specific):

• Primary stock solvent: DMSO is preferred due to high solvating power for polycyclic lactone–amine scaffolds and good compatibility with biological assay media upon dilution.
• Alternative solvents: DMF and NMP provide similar solubilization but can be less desirable in biological settings; ethanol can sometimes be used at lower stock concentrations; aqueous solubility is usually poor at neutral pH.
• pH considerations: Maintaining mildly acidic conditions helps preserve the E-ring lactone; avoid prolonged exposure to basic buffers which promote hydrolysis to the carboxylate form.

Solvent comparison (general):

• DMSO: high solubility, miscible with water; commonly tolerable at ≤0.1–0.5% v/v in cell assays.
• DMF/NMP: strong solvents but less biocompatible; use cautiously if assays are sensitive.
• MeOH/EtOH: moderate solubility; volatility can complicate dosing accuracy.
• Aqueous buffers: typically require cosolvent or cyclodextrin carriers.

Practical tips:

• Prepare 10–50 mM DMSO master stocks, aliquot to avoid freeze–thaw, and store at −80°C per item storage guidance.
• When dosing into aqueous systems, add stock last with vigorous mixing to avoid local supersaturation/precipitation; verify clarity and use 0.2 μm filtration if compatible with your application.

Storage and Reconstitution

Item-specific facts (from Product Data):

• Storage conditions: Store at −80°C.
• Shipped in: Dry ice packs + Cold packs.
• Appearance: Not specified for this item; refer to CoA/Spec Sheet.

General guidance (for camptothecin-class small molecules; not item-specific):

• Reconstitution: Dissolve in anhydrous DMSO to prepare concentrated stocks (e.g., 10–50 mM). Vortex/sonicate as needed. Avoid aqueous reconstitution to preserve the lactone.
• Aliquoting: Dispense single-use aliquots in amber vials or low-bind tubes to minimize adsorption and freeze–thaw cycles.
• Storage of solutions: Store DMSO stocks at −80°C, protected from light. Headspace should be minimized; consider inert gas overlay for long-term storage.
• Stability: Expect gradual degradation and/or lactone hydrolysis upon repeated thawing or prolonged exposure to moisture, light, or elevated temperatures. Discard aliquots showing precipitation, discoloration, or new peaks in LC–MS/HPLC.
• Handling: Thaw on ice, mix gently, and promptly return unused portions to −80°C. Record open/thaw dates to manage stock lifecycle.

Note: For definitive stability data (shelf life, retest date, freeze–thaw tolerance), consult the lot-specific CoA and SDS for Namitecan (CAS 372105-27-6).

Structure and Identity

Short overview: Namitecan is a small-molecule research compound listed in our screening library category. Limited item-specific identifiers are provided below; additional identifiers should be confirmed from the CoA/SDS or primary literature.

• SKU: N655466
• Product name: Namitecan
• CAS: 372105-27-6
• PubChem CID: 10950142
• InChIKey: Not specified for this item; refer to CoA/Spec Sheet.
• SMILES: Not specified for this item; refer to CoA/Spec Sheet.
• Molecular formula: Not specified for this item; refer to CoA/Spec Sheet.
• Molecular weight: Not specified for this item; refer to CoA/Spec Sheet.

Structural features (general chemistry knowledge):

• Namitecan is reported in the literature as a camptothecin-class analog (topoisomerase I inhibitor family), typically featuring a rigid pentacyclic scaffold with an E-ring lactone and a tertiary amine–bearing side chain on the A/B ring system. Verify exact substitution pattern from a primary source before structural work.
• 2D-description (literature, class-level): a fused polycyclic quinoline-like core (A–D rings) attached to a δ-lactone E-ring; common functional groups include aromatic rings, a lactone (prone to hydrolysis to the carboxylate at basic pH), and an aminoalkyl substituent that modulates solubility.

Important note: Do not use the class-level description as a substitute for a definitive structure. For structure-based design, docking, or analytical reference standards, obtain and confirm the exact structure (SMILES/InChI) from the CoA or a validated database entry corresponding to CAS 372105-27-6 / CID 10950142.

Synthetic Utility

Role in synthesis: Namitecan is a complex, bioactive small molecule and is not typically used as a reagent or building block in routine organic synthesis.

General synthetic chemistry notes for the scaffold (literature; class-level):

• Functional group landscape: polycyclic aromatic–lactone core with phenolic/alkoxy substituents and a basic aminoalkyl side chain. The E-ring lactone is sensitive to base and nucleophiles.
• Diversification strategies: late-stage functionalization via carbamate/urethane formation on phenolic groups; amide coupling or reductive amination on side-chain amines; Suzuki/Heck cross-couplings may be possible on suitably halogenated precursors during scaffold construction rather than on the final molecule.
• Protection/deprotection: maintain acidic conditions to preserve the lactone; employ acid-stable protecting groups (e.g., Boc on amines can be compatible if deprotected under carefully controlled acidic conditions that do not open the lactone).
• Stereochemistry: camptothecin scaffolds possess defined stereocenters critical for bioactivity; racemization or epimerization must be avoided.

If derivatization of Namitecan is intended:

• Confirm exact structure and reactive handles from CoA/literature for CAS 372105-27-6 before planning chemistry.
• Conduct small-scale feasibility under anhydrous, oxygen- and light-minimized conditions; monitor by LC–MS for lactone integrity and by NMR for side-chain modifications.

Target Specificity

Item-specific target information: Not specified for this item; refer to CoA/Spec Sheet and primary literature for definitive target, binding constants, and selectivity profile.

No additional target details are provided in the product data for SKU N655466.

Domande frequenti

How should this product be stored?

Store at ?80 °C. Ultra-low temperature storage is required to maintain the specified shelf life.

How is this product shipped?

This product ships frozen with dry ice and cold packs. Unpack on arrival and transfer it to the storage condition stated above; handle dry ice with insulated gloves in a ventilated area.

What are the CAS number, molecular formula and molecular weight?

The CAS Number is 372105-27-6, the molecular formula is C23H22N4O5, and the molecular weight is 434.44 g/mol.

What documentation is provided?

Available product documentation, including Certificates of Analysis (COA), Safety Data Sheets (SDS), and specification sheets, is shown in the product document area. Document availability and access follow the current site policy.