A-1165442 - ≥99% , CAS No.1221443-94-2

CAS: 1221443-94-2 Cat. No.: A646393 Formula: C₂₂H₂₀ClF₂N₃O₂ Molecular Weight: 431.86 PubChem CID: 46191567

GRADE & PURITY ≥99%

Storage

Store at -20°C

Shipped In

Ice chest + Ice pads

Overview

A-1165442 is a potent, competitive and orally available TRPV1 antagonist with an IC 50 of 9 nM for human TRPV1.

In Vitro

A-1165442 displays potent, competitive antagonism at recombinant human TRPV1 activated by capsaicin (IC 50 =9 nM) and incomplete blockade of acid-evoked response (62% block at 30 μM). A-1165442 possesses excellent selectivity (>100-fold) versus other members of the TRP family (TRPA1, TRPM8, TRPV2, TRPV3) and other receptors expressed in peripheral sensory neurons including P2X2/3, Cav2.2, Nav channels, and KCNQ2/3. A-1165442 shows minimal cross-reactivity upon evaluation (10 μM) in a broad screening panel (n=74, CEREP) of cell-surface receptors, ion channels, and enzymes. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

In Vivo

A-1165442 exhibits excellent pharmacological selectivity, has a favorable pharmacokinetic profile, and demonstrates good efficacy against osteoarthritis pain in rodents. Oral administration of A-1165442 prevents capsaicin-induced nocifensive behaviors in rats, with an ED 50 of 9.5 μmol/kg corresponding to plasma concentration of 420 ng/mL (970 nM). A single dose of A-1165442 produces a robust effect on grip force, with an ED 50 of 35 μmol/kg measured 1 h postdosing. Repeated dosing of A-1165442 results in an increase in potency relative to acute analgesic efficacy. No significant changes in core body temperature is observed in conscious rats dosed with A-1165442 and this temperature-neutral profile is maintained in conscious dogs . MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Form:Solid

IC50& Target:IC50: 9 nM (human TRPV1)

Specifications

Specifications & Purity

≥99%

Biochemical and Physiological Mechanisms

A-1165442 is a potent, competitive and orally available TRPV1 antagonist with an IC 50 of 9 nM for human TRPV1.

Storage

Store at -20°C

Shipped In

Ice chest + Ice pads

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

Action Type

ANTAGONIST

Purity

≥99%

Names and Identifiers

• Canonical Smiles: CC1=CC2=C(C=CC=C2NC(=O)NC3CC(OC4=C3C=CC(=C4)Cl)(CF)CF)C=N1
• IUPAC Name: 1-[(4R)-7-chloro-2,2-bis(fluoromethyl)-3,4-dihydrochromen-4-yl]-3-(3-methylisoquinolin-5-yl)urea
• InChIKey: VJJGAJAUECQWSZ-LJQANCHMSA-N
• INCHI: 1S/C22H20ClF2N3O2/c1-13-7-17-14(10-26-13)3-2-4-18(17)27-21(29)28-19-9-22(11-24,12-25)30-20-8-15(23)5-6-16(19)20/h2-8,10,19H,9,11-12H2,1H3,(H2,27,28,29)/t19-/m1/s1
• Isomeric SMILES: CC1=CC2=C(C=CC=C2NC(=O)N[C@@H]3CC(OC4=C3C=CC(=C4)Cl)(CF)CF)C=N1
• PubChem CID: 46191567
• MeSH Entry Terms: 1-(7-chloro-2,2-bis(fluoromethyl)chroman-4-yl)-3-(3-methylisoquinolin-5-yl)urea;A-1165442
• Molecular Weight: 431.86

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Organoheterocyclic compounds
    • Class Isoquinolines and derivatives

• Kingdom: Organic compounds
• Superclass: Organoheterocyclic compounds
• Class: Isoquinolines and derivatives
• Subclass: Not available
• Intermediate Tree Nodes: Not available
• Direct Parent: Isoquinolines and derivatives
• Alternative Parents: 1-benzopyrans Alkyl aryl ethers Methylpyridines Aryl chlorides Benzenoids Heteroaromatic compounds Ureas Oxacyclic compounds Azacyclic compounds Carbonyl compounds Hydrocarbon derivatives Organic oxides Organochlorides Alkyl fluorides Organofluorides Organonitrogen compounds
• Molecular Framework: Aromatic heteropolycyclic compounds
• Substituents: Chromane - Benzopyran - Isoquinoline - 1-benzopyran - Alkyl aryl ether - Methylpyridine - Aryl chloride - Aryl halide - Benzenoid - Pyridine - Heteroaromatic compound - Urea - Oxacycle - Ether - Azacycle - Organochloride - Organohalogen compound - Alkyl halide - Alkyl fluoride - Carbonyl group - Organic nitrogen compound - Hydrocarbon derivative - Organic oxide - Organic oxygen compound - Organofluoride - Organonitrogen compound - Organooxygen compound - Aromatic heteropolycyclic compound
• Description: This compound belongs to the class of organic compounds known as isoquinolines and derivatives. These are aromatic polycyclic compounds containing an isoquinoline moiety, which consists of a benzene ring fused to a pyridine ring and forming benzo[c]pyridine.
• External Descriptors: Not available

Data sources

1. Djoumbou Feunang Y, Eisner R, Knox C, Chepelev L, Hastings J, Owen G, Fahy E, Steinbeck C, Subramanian S, Bolton E, Greiner R, and Wishart DS. ClassyFire: Automated Chemical Classification With A Comprehensive, Computable Taxonomy. Journal of Cheminformatics, 2016, 8:61.

DOI: 10.1186/s13321-016-0174-y

Associated Targets(Human)

TRPV1 Tclin Transient receptor potential cation channel subfamily V member 1 (1 Activities)

Discover Target: TRPV1

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

TRPV1 Tclin Vanilloid receptor (8273 Activities)

Discover Target: TRPV1

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

CYP2D6 Tclin Cytochrome P450 2D6 (33882 Activities)

Discover Target: CYP2D6

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

CYP3A4 Tclin Cytochrome P450 3A4 (53859 Activities)

Discover Target: CYP3A4

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

Associated Targets(non-human)

Canis familiaris (36305 Activities)

Explore this target

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

Rattus norvegicus (775804 Activities)

Explore this target

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

Mechanisms of Action

Chemical and Physical Properties

• Solubility: DMSO : ≥ 100 mg/mL (231.56 mM) H2O : <0.1 mg/mL (insoluble)
• Molecular Weight: 431.900 g/mol
• XLogP3: 4.300
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 5
• Rotatable Bond Count: 4
• Exact Mass: 431.121 Da
• Monoisotopic Mass: 431.121 Da
• Topological Polar Surface Area: 63.300 Ų
• Heavy Atom Count: 30
• Formal Charge: 0
• Complexity: 609.000
• Isotope Atom Count: 0
• Defined Atom Stereocenter Count: 1
• Undefined Atom Stereocenter Count: 0
• Defined Bond Stereocenter Count: 0
• Undefined Bond Stereocenter Count: 0
• The total count of all stereochemical bonds: 0
• Covalently-Bonded Unit Count: 1

Application Protocols

Only protocols validated for this catalog item may appear here.

• Tested applications: Not specified for this item; refer to CoA/Spec Sheet.
• Recommended working ranges/dilutions: Not specified for this item; refer to CoA/Spec Sheet.
• Positive controls/assay references: Not specified for this item; refer to CoA/Spec Sheet.

General practice (for planning purposes only):

• Prepare DMSO stocks and perform serial dilutions in assay buffer/media to generate full concentration–response curves.
• Include matched vehicle controls and, when available, orthogonal probe controls.
• Document lot number, stock concentration, and exact vehicle composition in all records.

Biological Roles

This product is intended strictly for laboratory research. The following content provides general, literature-based context for small-molecule probes of intracellular pathways and how such compounds are typically utilized. No medical or clinical claims are made.

• Role as a chemical probe: Small molecules are widely used to acutely and reversibly modulate protein function, enabling time-resolved dissection of signaling, viability, and stress-response pathways in cells and lysates. Compared to genetic perturbations, chemical probes can provide rapid onset and tunable dosing.
• Pathway interrogation: By titrating concentration and exposure time, researchers can derive concentration–response relationships, estimate apparent cellular potency, and map pathway-specific biomarkers (e.g., phosphorylation states, transcriptional signatures, or proteolytic markers) that report on target engagement.
• Selectivity considerations: Off-target interactions are an inherent risk. Best practice involves orthogonal confirmation (e.g., phenocopy via genetic KO/knockdown, use of an inactive analog, or rescue experiments) to ensure on-target attribution.
• Pharmacology in vitro: Key parameters include biochemical potency (e.g., Ki/IC50 in purified systems), cellular potency (e.g., EC50 for a pathway readout), and time-dependence. These values are highly compound- and cell-model-dependent and must be established empirically under defined conditions.
• Formulation for biology: Stock solutions in DMSO are commonly employed; final solvent concentrations are typically maintained at ≤0.1–0.5% v/v to minimize vehicle effects.

Note: Compound-specific biological targets, mechanisms, or potencies are not specified in the current product data for A-1165442. Consult the primary literature or the batch documentation if target annotations are required for experimental design.

Buffer Applications

This item is not a buffering agent and is not used to control pH. However, buffer choice is important for its use in biochemical or cell-based assays.

General guidance (practice-based):

• Common assay buffers: PBS or HBSS for cell handling; Tris, HEPES, or phosphate buffers for enzyme and binding assays. Maintain physiological pH (≈7.2–7.6) unless the assay demands otherwise.
• Vehicle compatibility: Ensure the final DMSO fraction after dosing remains within the tolerance of your system (often ≤0.1–0.5% v/v for mammalian cells). Match vehicle across control and treated samples.
• Protein binding: Serum proteins (e.g., in FBS-containing media) can sequester hydrophobic compounds, shifting apparent potency. Consider reduced-serum or serum-free conditions for defined windows, with appropriate controls for cell health.
• Adsorption and precipitation: Use low-binding plastics and add compound stocks to vigorously mixed buffers to avoid local supersaturation and precipitation.
• Stability checks: If target pathways are sensitive to redox or metal ions, use chelators (e.g., 0.5–1 mM EDTA) only if validated not to interfere with the biology of interest.

Item-specific buffer recipes and pH ranges are not applicable; refer instead to your assay’s validated SOPs and include vehicle-only controls.

Green Alternatives

Green chemistry considerations are generally applied to solvents and bulk reagents. As a specialized small-molecule probe used at micromolar concentrations, A-1165442 has limited direct impact on process-scale green metrics. Nevertheless, greener practices can be implemented around its use:

• Solvent minimization: Prepare the highest practical concentration of DMSO stock compatible with assay requirements to reduce solvent volumes across dilutions.
• Solvent selection: Prefer DMSO over higher-toxicity aprotic solvents (e.g., DMF, NMP) for biological work. When possible, use aqueous buffers with minimal cosolvent.
• Packaging/waste: Consolidate experiments to minimize partial-vial wastage; dispose of solutions as hazardous organic waste according to local regulations.
• Energy use: Thaw and handle aliquots efficiently to limit repeated freeze–thaw cycles and unnecessary freezer door-open times.

Comparison (general context):

• DMSO vs DMF/NMP: DMSO offers favorable toxicity/biocompatibility profile and is widely accepted in bioassays; DMF/NMP are less desirable from an EHS standpoint.
• Aqueous vehicles with solubilizing excipients (e.g., cyclodextrins) can reduce DMSO percentages, but require validation for assay compatibility and may introduce additional variables.

Conclusion: Focus green improvements on solvent choice, aliquotting strategy, and waste reduction during the compound’s life cycle rather than on replacing the probe itself.

Pharmaceutical Uses

Research-use context only; no therapeutic or clinical use is intended or implied.

• Role in drug discovery workflows (general): Small-molecule probes are commonly used in target validation, pathway deconvolution, and as reference comparators in screening assays. They can inform structure–activity relationships (SAR) and guide medicinal chemistry optimization.
• Formulation studies (preclinical research): Investigators may evaluate solubility, stability, and compatibility in simple vehicles (e.g., DMSO, PEG-containing systems) to support in vitro and ex vivo experiments. Such activities remain strictly research-focused.
• Regulatory status: Not a pharmacopeial standard and not approved as an active pharmaceutical ingredient (API). Labeled for Research Use Only.
• Manufacturing/quality notes: Where applicable, request batch CoA to document purity, identity, and residual solvents for inclusion in research data packages.

Item-specific excipient roles, dosage forms, or compendial monographs are not provided for this product. Any evaluation of formulation properties should be conducted within institutional laboratory research guidelines and not for human or veterinary administration.

Physical Properties

Item-specific physical constants are not provided in the current listing.

• Appearance: Not specified for this item; refer to CoA/Spec Sheet.
• Melting point (MP): Not specified for this item; refer to CoA/Spec Sheet.
• Boiling point (BP): 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: Not specified for this item; refer to CoA/Spec Sheet.
• Refractive index/UV cutoff: Not specified for this item; refer to CoA/Spec Sheet.

General guidance for small-molecule tool compounds (literature/practice, not item-specific specifications):

• Many hydrophobic probes are formulated as concentrated DMSO stocks (e.g., 10–50 mM) and subsequently diluted into assay buffers. Actual solubility limits vary by structure and salt form.
• If aqueous use is intended, co-solvent systems (e.g., DMSO 0.1–1% v/v in PBS or culture media) and gentle warming/sonication can aid dissolution. Avoid excessive heating that may cause decomposition.
• Stability can depend on light, oxygen, and moisture exposure. Where details are unknown, minimize exposure and prepare single-use aliquots.

Always consult the batch CoA/SDS for definitive physical and stability parameters before experimental planning.

Quality & Grades

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

Context and expectations for research-use small molecules:

• Research Use Only (RUO): Supplied for laboratory research and chemical biology applications. Not for human or veterinary use, diagnostics, or food/cosmetic applications.
• If HPLC purity, residual solvent, or water content limits are critical, consult the batch CoA. When not specified at listing time, these attributes may still be controlled internally and documented per lot.
• Analytical verification typically includes HPLC/UPLC purity, LC–MS or HRMS for mass confirmation, and occasionally 1H/13C NMR. Confirm which analyses are provided for your lot.
• Stabilizers, salt forms, and polymorphs can influence solubility and bioassay performance. Where not specified, assume the free base/neutral form and verify on the CoA.

Practical guidance:

• For quantitative studies (e.g., IC50 determination), verify purity and identity on receipt; if needed, perform orthogonal checks (e.g., additional HPLC method, NMR in DMSO-d6).
• Record the exact lot number in data packages to ensure traceability and reproducibility across experiments.

Reaction & Applications

This item is a bioactive small-molecule tool compound and is not typically employed as a reagent or solvent in synthetic transformations.

Applicable research uses (general, non-clinical, literature/practice):

• Chemical biology: Probe-dependent modulation of intracellular pathways in cell lysates and live-cell assays to study target engagement, pathway dependency, and downstream signaling consequences.
• Target validation: Use in parallel with orthogonal chemotypes or genetic perturbations (e.g., RNAi/CRISPR) to strengthen causal inference for the pathway under study.
• SAR and profiling: Serve as a reference control within a chemotype family for comparative potency/selectivity profiling across biochemical and cellular panels.

Practical tips:

• Establish vehicle-only controls and, when applicable, inactive analog controls to distinguish on-target from off-target effects.
• Titrate over a logarithmic concentration range (e.g., 8–10 points) to map full concentration–response curves.
• Include time-course studies to capture kinetics of pathway modulation; steady-state effects may differ from acute responses.

If you require a synthetic building block for reactions, please consult our Building Blocks or Reagents categories; this listing is best utilized for assay-focused applications rather than chemical synthesis.

Reaction Conditions

Not typically applicable. A-1165442 is supplied as a bioactive small-molecule probe rather than as a reagent for chemical reactions.

Guidance for experimental use (assay context; practice-based, not item-specific specifications):

• Stock preparation: Commonly 10–50 mM in anhydrous DMSO, filtered through 0.2 µm PTFE if necessary. Prepare single-use aliquots to avoid freeze–thaw.
• Working concentrations: Determined empirically via concentration–response titration in the specific assay model. Include vehicle-only controls.
• Incubation parameters: Time- and temperature-dependence should be optimized; many cellular assays are performed at 37°C with exposure ranging from minutes to 24–72 hours depending on endpoint.
• Light/oxidation sensitivity: When details are unknown, protect from light and minimize air exposure.

If you require reaction condition guidance for synthetic chemistry, select a reagent designed for that purpose; this listing is not intended for synthetic transformations.

Safety & Handling

Safety data for this specific item are not fully specified in the current record.

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

General laboratory precautions (good practice; not item-specific):

• Handle in a fume hood with appropriate PPE: lab coat, safety glasses, and chemical-resistant gloves (e.g., nitrile). Avoid inhalation of dust/aerosols and contact with skin/eyes.
• Avoid incompatible materials until confirmed via SDS (strong oxidizers/reducers, strong acids/bases) and segregate from foodstuffs and non-lab areas.
• Prepare DMSO stock solutions using clean, dry glassware; wipe external vial surfaces to remove residues. Cap tightly to limit solvent loss and moisture ingress.
• If material is provided as a dry solid, minimize static and dust generation; consider weighing boats with antistatic tools.

First-aid overview (consult SDS for authoritative guidance):

• Skin/eye contact: Immediately rinse with copious water for ≥15 minutes; remove contaminated clothing. Seek medical evaluation if irritation persists.
• Inhalation: Move to fresh air; monitor for respiratory irritation; seek medical attention as needed.
• Ingestion: Rinse mouth; do not induce vomiting unless directed by medical personnel; seek immediate medical attention.

Waste disposal: Collect solutions and contaminated disposables as organic hazardous waste. Follow institutional and local regulations. Always defer to the SDS and institutional EHS requirements.

Solvent Selection

This product is a small-molecule chemical probe rather than a bulk process solvent. Solvent selection therefore focuses on stock-solution preparation and assay compatibility rather than synthetic use.

General guidance (literature/practice; not item-specific specifications):

• Primary solvent for stock: DMSO is typically preferred due to broad solvating power and compatibility with cell-based and biochemical assays at low final percentages (commonly ≤0.1–0.5% v/v).
• Alternative co-solvents: DMF or ethanol can dissolve certain chemotypes but may be less biocompatible; evaluate assay tolerance if used (e.g., keep ≤0.1% v/v in sensitive cells).
• Aqueous compatibility: If direct aqueous solubility is limited, prepare a concentrated DMSO stock (e.g., 10–50 mM) and dilute into buffer/media with vigorous mixing. Add the DMSO solution last to well-mixed aqueous media to minimize precipitation.
• Buffers: Physiological buffers (PBS, HBSS) or assay-specific buffers (HEPES, Tris) are commonly used; maintain consistent pH and ionic strength during compound addition.
• Adsorptive losses: Low-binding plasticware or glass vials help reduce nonspecific adsorption for hydrophobic compounds.

Small comparison (general):

• DMSO: highest solvency, excellent freezing stability, broadly accepted in biological assays.
• Ethanol: good solvency; higher volatility; may affect membrane integrity at >0.5% v/v.
• Aqueous with cosolvent or cyclodextrins: improved delivery for poorly soluble scaffolds; requires optimization and controls.

Always verify the final vehicle composition is matched in vehicle controls.

Storage & Reconstitution

Item-specific instructions:

• Storage conditions (Product Data): Store at -20°C.
• Shipping (Product Data): Shipped in ice chest + ice pads.

General best practices (not item-specific specifications):

• Upon receipt: Allow the shipping container to equilibrate to room temperature before opening to avoid condensation on cold vials. Immediately return unopened vials to -20°C.
• Light/moisture protection: Store in the original, tightly capped container; protect from light and humidity. If provided as a dry solid, consider using a desiccant and an inert atmosphere in secondary containment.
• Aliquoting: If frequent use is anticipated, prepare single-use aliquots of DMSO stock solutions in amber vials or low-bind tubes to minimize freeze–thaw and adsorption losses.
• Reconstitution: Dissolve the compound in anhydrous DMSO to a convenient concentration (e.g., 10–50 mM), vortex to clarity, and, if needed, gently warm (≤37°C) or sonicate briefly. Filter through a 0.2 µm PTFE membrane if particulate persists. Record the exact concentration and date.
• Working solutions: Dilute the DMSO stock into prewarmed buffer/media with vigorous mixing. Keep final DMSO at assay-tolerated levels (often ≤0.1–0.5% v/v). Use freshly prepared working solutions when possible.
• Stability: In the absence of item-specific stability data, limit storage of solutions to short periods (days at 2–8°C; weeks to months at -20°C) and monitor by LC–MS/HPLC as needed.

Always defer to the product’s CoA and SDS for definitive handling and stability guidance.

Structure & Identity

Brief overview: A-1165442 is supplied as a research-use small-molecule tool compound. Limited structural identifiers are available in the current product record.

• SKU: A646393
• Product name: A-1165442 (research-use chemical probe)
• CAS: 1221443-94-2 (Product Data)
• PubChem CID: 46191567 (Product Data)
• InChIKey: 380528 (Product Data; note: this entry is non-standard length for an InChIKey; refer to CoA/SDS for confirmation)
• 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 description (general):

• Functional groups and ring systems: Not specified for this item; refer to CoA/Spec Sheet.
• Stereochemistry: Not specified for this item; refer to CoA/Spec Sheet.
• 2D structure (verbal): Not specified for this item; refer to CoA/Spec Sheet.

Notes:

• Identity confirmation should rely on the provided CAS/CID and the Certificate of Analysis for batch-specific structural and analytical details (e.g., HPLC, NMR, MS).

Synthetic Utility

This product is a finished small-molecule probe and is not positioned as a synthetic building block or reagent.

• Not typically used as: coupling partner, catalyst/ligand, protecting group reagent, or solvent.
• If chemical modification or derivatization is desired (e.g., to prepare tagged analogs for pull-downs or imaging), consult the primary literature for disclosed synthetic routes to related chemotypes and identify suitable vectors for functionalization. Such work should be undertaken by experienced synthetic chemists with appropriate route-scouting and analytical controls.

For general synthetic needs, please refer to our dedicated Reagents, Catalysts/Ligands, and Building Blocks categories, where you will find substances with clearly defined reactivity profiles and handling recommendations.

Target Specificity

Only product-data–verified target details may appear here.

• Target/Pathway: Not specified for this item; refer to CoA/Spec Sheet.
• Species reactivity or selectivity: Not specified for this item; refer to CoA/Spec Sheet.
• Mechanism of action: Not specified for this item; refer to CoA/Spec Sheet.

Note: Researchers may consult the primary literature for background on this compound name; however, any study-specific target assignments should be independently verified under your assay conditions.