ART558 - Moligand™,≥99% , CAS No.2603528-97-6

CAS: 2603528-97-6 Cat. No.: A648595 Formula: C₂₁H₂₁F₃N₄O₂ Molecular Weight: 418.41 PubChem CID: 156068882

GRADE & PURITY Moligand™, ≥99%

Synonyms

2-Pyrrolidinecarboxamide, 1-[3-cyano-6-methyl-4-(trifluoromethyl)-2-pyridinyl]-3-hydroxy-N-methyl-N-(3-methylphenyl)-, (2S,3R)- | (2S,3R)-1-(3-Cyano-6-methyl-4-(trifluoromethyl)pyridin-2-yl)-3-hydroxy-N-methyl-N-(m-tolyl)pyrrolidine-2-carboxamide

Storage

Store at 2-8°C,Protected from light,Argon charged,Desiccated

Shipped In

Wet ice

Overview

ART558 is a potent, selective, low molecular weight, allosteric DNA polymerase activity of Polθ inhibitor (IC50=7.9 nM). ART558 inhibits the primary Polθ-mediated DNA repair process, namely Theta-mediated end joining, without targeting non-homologous end joining.ART558 can be used for the research of cancer.

Specifications

Synonyms

2-Pyrrolidinecarboxamide, 1-[3-cyano-6-methyl-4-(trifluoromethyl)-2-pyridinyl]-3-hydroxy-N-methyl-N-(3-methylphenyl)-, (2S,3R)- | (2S,3R)-1-(3-Cyano-6-methyl-4-(trifluoromethyl)pyridin-2-yl)-3-hydroxy-N-methyl-N-(m-tolyl)pyrrolidine-2-carboxamide

Specifications & Purity

Moligand™, ≥99%

Biochemical and Physiological Mechanisms

ART558 is a nanomolar potent, selective, low molecular weight, allosteric DNA polymerase activity of Polθ inhibitor ( IC 50 =7.9 nM). ART558 can be used for the research of cancer.

Storage

Store at 2-8°C,Protected from light,Argon charged,Desiccated

Shipped In

Wet ice

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

Grade

Moligand™

Purity

≥99%

Names and Identifiers

• Canonical Smiles: CC1=CC(=CC=C1)N(C)C(=O)C2C(CCN2C3=NC(=CC(=C3C#N)C(F)(F)F)C)O
• IUPAC Name: (2S,3R)-1-[3-cyano-6-methyl-4-(trifluoromethyl)pyridin-2-yl]-3-hydroxy-N-methyl-N-(3-methylphenyl)pyrrolidine-2-carboxamide
• InChIKey: YHMDHAMZFMNMTF-MSOLQXFVSA-N
• INCHI: 1S/C21H21F3N4O2/c1-12-5-4-6-14(9-12)27(3)20(30)18-17(29)7-8-28(18)19-15(11-25)16(21(22,23)24)10-13(2)26-19/h4-6,9-10,17-18,29H,7-8H2,1-3H3/t17-,18+/m1/s1
• Isomeric SMILES: CC1=CC(=CC=C1)N(C)C(=O)[C@@H]2[C@@H](CCN2C3=NC(=CC(=C3C#N)C(F)(F)F)C)O
• PubChem CID: 156068882
• Molecular Weight: 418.41

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Organic acids and derivatives
    • Class Carboxylic acids and derivatives
      • Subclass Amino acids, peptides, and analogues
        • Level5 Amino acids and derivatives
          • Level6 Alpha amino acids and derivatives
            • Level7 Proline and derivatives

• Kingdom: Organic compounds
• Superclass: Organic acids and derivatives
• Class: Carboxylic acids and derivatives
• Subclass: Amino acids, peptides, and analogues
• Intermediate Tree Nodes: Amino acids and derivatives - Alpha amino acids and derivatives
• Direct Parent: Proline and derivatives
• Alternative Parents: Alpha amino acid amides Anilides Pyrrolidinecarboxamides Polyhalopyridines Dialkylarylamines 3-pyridinecarbonitriles Methylpyridines Hydroxypyridines Aminopyridines and derivatives 2-halopyridines N-acyl amines Imidolactams Tertiary carboxylic acid amides Heteroaromatic compounds Secondary alcohols Propargyl-type 1,3-dipolar organic compounds Nitriles Carboximidamides Azacyclic compounds Amidines Organopnictogen compounds Organofluorides Organic oxides Hydrocarbon derivatives Alkyl fluorides
• Molecular Framework: Aromatic heteromonocyclic compounds
• Substituents: Proline or derivatives - Alpha-amino acid amide - Anilide - 3-pyridinecarbonitrile - Polyhalopyridine - Dialkylarylamine - Tertiary aliphatic/aromatic amine - Pyrrolidine-2-carboxamide - Pyrrolidine carboxylic acid or derivatives - 2-halopyridine - Methylpyridine - Hydroxypyridine - Aminopyridine - Imidolactam - Benzenoid - Pyridine - N-acyl-amine - Monocyclic benzene moiety - Heteroaromatic compound - Tertiary carboxylic acid amide - Pyrrolidine - Tertiary amine - Secondary alcohol - Carboxamide group - Azacycle - Organoheterocyclic compound - Organic 1,3-dipolar compound - Propargyl-type 1,3-dipolar organic compound - Carboximidamide - Nitrile - Carbonitrile - Amidine - Organic nitrogen compound - Organic oxygen compound - Organopnictogen compound - Organic oxide - Hydrocarbon derivative - Organooxygen compound - Organonitrogen compound - Organofluoride - Organohalogen compound - Amine - Alkyl halide - Alkyl fluoride - Alcohol - Aromatic heteromonocyclic compound
• Description: This compound belongs to the class of organic compounds known as proline and derivatives. These are compounds containing proline or a derivative thereof resulting from reaction of proline at the amino group or the carboxy group, or from the replacement of any hydrogen of glycine by a heteroatom.
• 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)

DLD-1 (17511 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 : 170 mg/mL (406.30 mM; Need ultrasonic)
• Sensitivity: light sensitive，Moisture sensitive
• Molecular Weight: 418.400 g/mol
• XLogP3: 3.900
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 8
• Rotatable Bond Count: 3
• Exact Mass: 418.162 Da
• Monoisotopic Mass: 418.162 Da
• Topological Polar Surface Area: 80.500 Ų
• Heavy Atom Count: 30
• Formal Charge: 0
• Complexity: 679.000
• Isotope Atom Count: 0
• Defined Atom Stereocenter Count: 2
• 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

Item-specific facts (from Product Data)

• No validated application protocols are provided for ART558.

General protocols for screening ligands (not item-specific)

1. DMSO stock preparation

• Warm vial to room temperature under low light. Briefly purge headspace with argon if available. Add anhydrous DMSO to achieve 10–50 mM nominal concentration. Vortex/sonicate to dissolve completely. Record exact mass/volume for traceability.
• Optional: confirm concentration by UV (if ε known) or qNMR.

2. Serial dilution for assays

• Prepare 3-fold serial dilutions in DMSO (10–12 points). Transfer to assay buffer to reach final vehicle ≤0.5–1.0% DMSO. Include vehicle controls and, if available, a positive control ligand.

3. Solubility/aggregation check

• Inspect for precipitation/turbidity after dilution; if observed, increase surfactant to 0.01–0.05% or reduce top concentration. Consider filtration (0.2 µm PTFE) when assay-compatible.

4. Plate handling

• Use low-binding, black (fluorescence) or white (luminescence) plates as appropriate. Seal plates to limit evaporation; equilibrate to assay temperature before reading.

Documentation

• Record lot number, preparation date, and storage conditions for reproducibility. For regulated studies, attach CoA/SDS to the experiment record.

Biological Roles

Item-specific facts (from Product Data)

• No target, pathway, or mechanism information is provided for ART558.

General guidance (not item-specific)

• As a Moligand™ screening ligand, ART558 may be used to interrogate protein–ligand interactions in enzymatic, receptor, or protein–protein interaction systems. Any inferred biological role must be established empirically via assays and orthogonal confirmation (e.g., biophysics and chemoproteomics when appropriate).
• When exploring potential roles, consider off-target assessment using selectivity panels, counterscreens, and orthogonal phenotypic assays to mitigate false positives (assay interference, redox cycling, aggregation, fluorescence quenching).
• ADME profiling (permeability, solubility, microsomal stability, and plasma protein binding) can contextualize observed activity. Photostability and oxidative stability testing may be relevant given the recommended light and inert-atmosphere storage.

Important

• No clinical or diagnostic use is implied. For research use only, as stated by the manufacturer. Any proposed biological function must be supported by user-generated data on the specific system of interest.

Buffer Applications

Not typically applicable

• ART558 is a small-molecule screening ligand, not a buffering agent. No buffer capacity or pKa information is provided.

Practical note

• For assays, select buffers based on the biology (e.g., HEPES, PBS, Tris) and ensure vehicle (DMSO/EtOH) and any surfactant levels are compatible with the readout and target. Conduct stability checks of ART558 in the chosen buffer system once the structure/stability data are available.

Green Alternatives

Context

• Without a disclosed structure, solvent and process choices for ART558 cannot be optimized item-specifically. However, greener handling of screening compounds often centers on solvent selection and waste minimization.

Greener considerations (general)

• Prefer aqueous assay buffers with minimal DMSO where compatible; target ≤0.5% v/v.
• Consider biobased dipolar aprotics (e.g., Cyrene, PolarClean) for preparative operations when physicochemical compatibility allows; verify assay/background effects first.
• Use amber glass and reusable consumables to reduce plastic waste when chemically compatible.
• Consolidate plate operations to reduce dead volumes and rinse waste; adopt sealed low-evaporation plates to minimize rework.

Trade-offs (general)

• Cyrene and PolarClean can have higher viscosity and limited miscibility with water versus DMSO; solubility and assay interference must be validated.
• Ethanol is greener than DMF/DMSO but may be less effective for highly lipophilic ligands and can disrupt cells at low percentages.

Summary table (general)

• DMSO: excellent solvency; moderate EHS; proven assay utility; minimize % and waste.
• Ethanol: renewable, lower toxicity; limited solvency for very nonpolar chemotypes.
• Cyrene/PolarClean: greener profile; check compatibility/solubility and optics before adoption.

Pharmaceutical Uses

Not typically applicable

• ART558 is provided for research use only as part of a small-molecule screening collection. It is not supplied as an excipient, not covered by pharmacopeial monographs, and is not intended for formulation for human or veterinary use.

Research formulation context (general)

• For in vitro work, DMSO stocks are standard; for exploratory in vivo method development (if permitted within your institution and regulations), appropriate toxicology, stability, and formulation studies would be required first. Aladdin Scientific does not provide any clinical-use claims for this product.

Physical Properties

Item-specific facts (from Product Data)

• Appearance: Not specified for this item; refer to CoA/Spec Sheet.
• Physical form/phase: Not specified for this item; refer to CoA/Spec Sheet.
• Solubility: Not specified for this item; refer to CoA/Spec Sheet.
• Other physicochemical parameters (mp, bp, density, logP, pKa, UV cutoff, refractive index): Not specified for this item; refer to CoA/Spec Sheet.

General guidance (literature/typical for screening compounds — not item-specific)

• Many discovery ligands are supplied as dry solids or as argon-charged desiccated vials, indicating potential sensitivity to moisture/oxygen or photolability (consistent with: store at 2–8°C, protected from light, argon charged, desiccated).
• Typical stock preparation solvents: anhydrous DMSO (most common), DMF, or ethanol; aqueous solubility often requires cosolvent or surfactant (e.g., 0.5–2% DMSO, 0.01–0.05% Tween-20) depending on the chemotype.
• Hygroscopicity and polymorphism can influence apparent solubility; pre-dry under argon/vacuum if specified by the CoA.

Practical notes

• Verify concentration by weight-on-vial or qNMR/UV if an extinction coefficient is available (not provided here).
• Use a small solubility screen (DMSO, DMF, MeOH, EtOH, PBS + cosolvent) at the intended working concentration to confirm compatibility prior to assay deployment.

Quality & Grades

Item-specific facts (from Product Data)

• Grade/Purity designation: Moligand™
• Supplied condition: Store at 2–8°C, protected from light, argon charged, desiccated; shipped on wet ice.
• Assay/purity %, residual solvents, and elemental limits: Not specified for this item; refer to CoA/Spec Sheet.

What Moligand™ indicates (program description — general, not item-specific)

• Moligand™ denotes inclusion in Aladdin’s research screening collection of small-molecule ligands intended for hit finding, SAR, and probe development.
• Typical expectations for screening-grade ligands: analytical verification by LC/MS and/or 1H NMR; trace impurity control suited for biochemical/biophysical assays; packaging under inert atmosphere when sensitivity is known or suspected.

Implications for users

• Light/oxygen/moisture precautions suggest attention to handling to preserve assay reproducibility. Open only in low-humidity environments; recap and purge with argon/nitrogen when practical.
• For chromatography- or spectroscopy-critical work (HPLC-UV, SPR, MST), request low-UV or metal impurity data if relevant to your platform. If exact thresholds are required, rely on the lot-specific CoA.

Documentation

• For regulated workflows, retain CoA/SDS with lot traceability. Where specific numeric specs are required (water content, peroxides, metals, UV cutoff), they are Not specified for this item; refer to CoA/Spec Sheet.

Reaction & Applications

Relevance note

• ART558 is supplied as a Moligand™ small-molecule library member intended primarily for screening and ligand-discovery workflows, not as a general synthetic reagent. No specific reactivity profile is provided in the Product Data.

Applications in discovery (general, not item-specific)

• Biochemical inhibition/activation screens: enzyme assays (fluorometric/absorbance), binding displacement, and activity-based profiling.
• Biophysical binding: SPR, BLI, MST, DSF/TSA, nanoDSF, NMR titrations, ITC.
• Cellular/phenotypic assays: reporter readouts, viability/cytotoxicity windows, target engagement (e.g., CETSA) — validate DMSO tolerance and vehicle controls.
• Computational chemistry: docking, pharmacophore mapping, and free-energy perturbation when structure is available.

Assay execution tips

• Prepare concentrated, accurately quantified DMSO stocks; verify by LC/UV or qNMR when feasible.
• Use serial dilutions across 8–12 points (typically 3-fold) to define potency curves; ensure top concentration is below solubility limit in final assay medium.
• Control aggregation artifacts by adding low % detergent and monitoring Hill slopes/outlier counterscreens.
• For light- or air-sensitive compounds (suggested by packaging), handle under low light and inert atmosphere, minimizing air exposure.

Reaction Conditions

Not applicable to this item’s primary use

• No synthetic reaction use or conditions are specified for ART558. It is supplied for biochemical/biophysical screening rather than as a reagent.

Assay-condition considerations (general, not item-specific)

• Temperature: many enzyme and binding assays run at 20–25°C; cell-based assays typically at 37°C with 5% CO2.
• Solvent vehicle: maintain ≤0.5–1.0% DMSO in final assays unless validated otherwise.
• Light/oxygen sensitivity: suggested by storage conditions; perform preparation and incubations under reduced light and minimize exposure to air when feasible.
• Time courses: pilot time-dependence studies (e.g., 10–120 min) can reveal slow-binding or time-dependent effects.

Safety & Handling

Item-specific hazards (from Product Data)

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

General laboratory precautions (not item-specific; defer to SDS for authoritative guidance)

• Handle in a fume hood with appropriate PPE: lab coat, safety glasses, and suitable chemically resistant gloves (e.g., nitrile). Avoid inhalation of dust/aerosols and contact with skin/eyes.
• Given storage instructions (2–8°C, protected from light, argon charged, desiccated), treat as potentially moisture/air/light sensitive. Minimize headspace air exposure; recap promptly; purge with inert gas if feasible.
• Avoid incompatible conditions typical for organic ligands: strong oxidants, strong acids/bases, and prolonged UV exposure unless stability is known.
• In case of contact: rinse skin/eyes with water for at least 15 minutes; remove contaminated clothing. If inhaled, move to fresh air. If swallowed, rinse mouth; do not induce vomiting unless directed. Seek medical attention as per SDS.
• Spill/cleanup: avoid dust generation; absorb solutions with inert material; collect in properly labeled waste for organic hazardous disposal.

Notes

• Always consult the lot-specific SDS for transport, toxicology, environmental fate, and disposal requirements.

Solvent Selection

Item-specific facts (from Product Data)

• No solvent preferences or solubility values are provided for ART558.

General guidance for small-molecule ligands (literature/practice — not item-specific)

• Primary solvent for stocks: anhydrous DMSO (5–50 mM typical). Consider DMF or ethanol if DMSO is incompatible with the assay.
• Aqueous use: dilute DMSO stocks into assay buffer to ≤0.5–1.0% final DMSO to minimize vehicle effects. Include vehicle controls.
• If the compound is hydrophobic: add 0.01–0.05% nonionic surfactant (Tween-20, Pluronic F-127) or use co-solvent blends (e.g., 5–20% PEG-400 in buffer) while confirming target/assay tolerance.
• For light-sensitive chemotypes: use amber vials and minimize exposure during solution prep and transfers.

Small comparison (general)

• DMSO: highest solvency for diverse chemotypes; widely assay-compatible at ≤1% v/v.
• DMF: similar solvency; verify cytotoxicity/background effects in cell-based assays.
• Ethanol/MeOH: useful for moderately polar ligands; higher volatility and potential assay interference.

Practical tips

• Perform a micro-solubility screen at intended working concentration and temperature. Use sonication and brief warming (≤37°C) if compatible. Filter (0.2 µm PTFE) to remove particulates where appropriate.

Storage & Reconstitution

Item-specific facts (from Product Data)

• Storage conditions: Store at 2–8°C, protected from light, argon charged, desiccated.
• Shipped in: Wet ice.

Item-specific notes

• The combination of light protection, inert gas, and desiccation indicates potential light and moisture/air sensitivity. Keep vial tightly closed; minimize air exposure during openings; consider purging with inert gas after each use.

General guidance (not item-specific)

• Reconstitution: Prepare stocks in anhydrous solvent (commonly DMSO) under low light. Use amber vials or foil wrap. Record exact concentration and solvent.
• Aliquoting: To minimize freeze–thaw and headspace exposure, split into single-use aliquots immediately after initial dissolution.
• Short-term storage of solutions: 2–8°C for hours to days, if stability is known. For longer-term storage of DMSO stocks, many screening ligands are kept at −20°C to −80°C; confirm stability for ART558 experimentally or via CoA before deviating from the labeled storage condition.
• Thawing/handling: Warm sealed aliquots to room temperature before opening to avoid condensation; mix gently to re-homogenize.

Specifications not provided

• Appearance, water content, stabilizers, and solution stability parameters: Not specified for this item; refer to CoA/Spec Sheet.

Disposal

• Dispose of unused solutions and residues as organic hazardous waste in accordance with institutional and local regulations.

Structure & Identity

Item-specific facts (from Product Data)

• SKU: A648595 (ART558)
• CAS: 2603528-97-6
• PubChem CID: 156068882
• InChIKey: 437448 (as provided)
• 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.
• Category: Small-molecule/compound library (Moligand™ collection)

Interpretive notes

• Structural features, ring systems, functional groups, and stereochemistry cannot be summarized without a structure. Please consult the CoA/SDS or request the structure disclosure if available under your screening agreement.
• 2D description: Not available. If you require a 2D/3D depiction for docking or cheminformatics, contact Aladdin Scientific for data under appropriate terms.

Data integrity

• Where a value is not listed above, it is intentionally left “Not specified for this item; refer to CoA/Spec Sheet.” to avoid unintended assumptions. Always confirm identity via lot-specific CoA prior to regulated or data-critical use.

Synthetic Utility

Relevance note

• As a Moligand™ library member, ART558 is intended for screening rather than as a synthetic reagent or building block. No functional group or reactivity data are provided.

General commentary (not item-specific)

• If structural disclosure is available and the compound bears synthetically useful handles (e.g., aryl halides, boronates, amines, acids), analog generation via cross-coupling, amidation, or nucleophilic substitution may support SAR campaigns.
• Absent a disclosed structure, treat the material as a terminal screening entity. For derivatization or linker installation (e.g., biotinylation, photoaffinity tags), request structural and IP-clearance information from Aladdin prior to custom synthesis.

Target Specificity

Item-specific facts (from Product Data)

• No target, family, or selectivity profile is provided for ART558.

Guidance (not item-specific)

• Establish target specificity through primary activity screening followed by orthogonal validation and selectivity panels against close homologs and unrelated counterscreens. Use biophysical confirmation (SPR/MST/ITC/DSF) and, where appropriate, chemoproteomic pull-downs or CETSA for cellular target engagement.
• Track potential assay interferences (absorbance/fluorescence overlap, redox cycling, aggregation) using PAINS and colloidal aggregation filters; confirm with detergent sensitivity and dynamic light scattering when necessary.