BB-Cl-Amidine - Moligand™, ≥98% , CAS No.1802637-39-3

CAS: 1802637-39-3 Cat. No.: B1021758 Fórmula: C₂₆H₂₆ClN₅O Peso molecular: 459.97

GRADE & PURITY Moligand™, ≥98%

Storage

Store at -20°C,Argon charged

Shipped In

Ice chest + Ice pads

Specifications

Especificações e pureza

Moligand™, ≥98%

Condições de armazenamento de armazenamento

Store at -20°C,Argon charged

Enviado em

Ice chest + Ice pads

Este produto requer transporte de cadeia fria. Serviços terrestres e outros serviços econômicos não estão disponíveis.

Grau

Moligand™

Tipo de ação

INHIBITOR

Pureza

≥98%

Nomes e identificadores

• Sorrisos canónicos: C1=CC=C(C=C1)C2=CC=C(C=C2)C(=O)NC(CCCN=C(CCl)N)C3=NC4=CC=CC=C4N3
• IUPAC Name: N-[(1S)-4-[(1-amino-2-chloroethylidene)amino]-1-(1H-benzimidazol-2-yl)butyl]-4-phenylbenzamide
• InChIKey: YDOAWJHYHGBQFI-QHCPKHFHSA-N
• INCHI: 1S/C26H26ClN5O/c27-17-24(28)29-16-6-11-23(25-30-21-9-4-5-10-22(21)31-25)32-26(33)20-14-12-19(13-15-20)18-7-2-1-3-8-18/h1-5,7-10,12-15,23H,6,11,16-17H2,(H2,28,29)(H,30,31)(H,32,33)/t23-/m0/s1
• SMILES isoméricas: C1=CC=C(C=C1)C2=CC=C(C=C2)C(=O)N[C@@H](CCCN=C(CCl)N)C3=NC4=CC=CC=C4N3
• Peso molecular: 459.97

Propriedades químicas e físicas

• Peso molecular: 460.000 g/mol
• XLogP3: 4.300
• Hydrogen Bond Donor Count: 3
• Hydrogen Bond Acceptor Count: 3
• Rotatable Bond Count: 9
• Exact Mass: 459.183 Da
• Monoisotopic Mass: 459.183 Da
• Topological Polar Surface Area: 96.200 Ų
• Heavy Atom Count: 33
• Formal Charge: 0
• Complexity: 645.000
• 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 item-specific, tested application protocols can be listed here.

• Validated applications (WB, IHC, IF, FC, enzyme assay conditions, recommended dilutions, positive controls): Not specified for this item; refer to CoA/Spec Sheet.

General guidance for planning (not item-specific):

• Prepare DMSO stock; conduct a small solubility and stability check in your intended buffer and temperature.
• Run a short time-course to capture covalent kinetics and determine optimal preincubation time.
• Include vehicle controls and orthogonal readouts (e.g., anti-citrulline immunoblot and enzyme activity) to corroborate effects.

Biological Roles

Use context: For research use only. No medical or clinical claims are made.

Literature context for BB‑Cl‑amidine–type probes:

• Target class: Peptidyl arginine deiminases (PADs, e.g., PAD1–4, PAD6), Ca2+-dependent enzymes that catalyze conversion of peptidyl-arginine to peptidyl-citrulline (citrullination), modulating chromatin structure, transcription, and protein function.
• Mechanism: Haloacetamidine inhibitors act as electrophilic, mechanism-based covalent inhibitors that mimic arginine side chains and capture active-site nucleophiles, leading to time-dependent inactivation.
• Research applications:
  • Dissecting roles of citrullination in epigenetic regulation, neutrophil extracellular trap (NET) formation, and immune signaling (basic biology context).
  • Chemical validation of PAD involvement in specific signaling axes using gain/loss-of-function combined with inhibitor treatment.
• Selectivity considerations: Substituent and cap-group modifications in BB-series inhibitors are reported to tune isozyme selectivity and cell permeability; researchers often perform target deconvolution (e.g., chemical proteomics) to confirm isoform engagement.

Assay considerations (general):

• Include time dependence in kinetic analyses to capture covalent mechanisms.
• Monitor global and substrate-specific citrullination by anti-citrulline immunoblotting or MS-based proteomics after treatment.
• Control for off-target alkylation using cysteine-reactive scavengers in counter-screens, recognizing that excessive scavenger can mask on-target engagement.

Consult primary literature for isoform-specific data relevant to your system and confirm findings with orthogonal genetic methods.

Buffer Applications

This product is not a buffer or buffering agent. It is a small-molecule biochemical probe.

Practical notes for use in buffered systems (general guidance):

• Stock preparation: Prepare concentrated stocks in anhydrous DMSO (e.g., 10–50 mM), then dilute into assay buffer immediately before use.
• Compatible buffers: Common enzyme assay buffers (HEPES, Tris, PBS) are typically used. Verify that buffer components do not contain high concentrations of free thiols or strong nucleophiles that can quench haloacetamidine electrophiles.
• pH considerations: Amidine groups are strongly basic; near-neutral pH (7.0–7.6) is generally compatible with PAD assays while balancing protein stability. Avoid high pH (>8.5) which can accelerate hydrolysis of electrophilic moieties.
• Vehicle control: Match final DMSO percentage in all samples, positive controls, and blanks to isolate compound effects from solvent effects.

If a specific buffer recipe or pH stability range is required for your assay, consult the primary literature for your target enzyme and validate empirically.

Green Alternatives

Context: BB‑Cl‑Amidine is a specialized covalent biochemical probe; substitution is generally driven by biological selectivity and mechanistic suitability rather than conventional “solvent green metrics.” That said, greener choices can be considered in two dimensions: solvent systems and probe design.

Greener solvent choices (general guidance):

• Prefer aqueous buffers with minimal DMSO content while maintaining solubility. Where feasible, use 0.1–1% DMSO cosolvent instead of higher loadings.
• Avoid chlorinated handling solvents (e.g., CH2Cl2) for solution prep and cleaning; substitute with ethyl acetate or cyclopentyl methyl ether (CPME) when compatible.

Probe-design/selection considerations (literature-based; not item-specific):

• Non-halogenated electrophiles: In some studies, non-chlorinated amidine-based PAD inhibitors (e.g., “BB‑amidine” analogs) are used to reduce potential off-target alkylation by chloride leaving groups. Tradeoff: may reduce covalent efficiency and potency.
• Reversible inhibitors: Switching to reversible PAD inhibitors (where appropriate) can lessen concerns around persistent covalent modification and downstream waste handling, but may require higher concentrations and continuous exposure.

Tradeoffs snapshot:

• Covalent haloacetamidine (e.g., BB‑Cl‑amidine): High target engagement at low doses; potential broader nucleophile reactivity; careful waste management.
• Non-halogenated/reversible alternatives: Potentially greener/reactivity-tuned; may require more material, longer incubations, and tighter selectivity validation.

Always validate biological performance after any “green” substitution, as selectivity and efficacy are typically the dominant constraints.

Pharmaceutical Uses

This product is supplied strictly for laboratory research use and is not intended for human or veterinary applications, diagnostics, or therapeutic use.

Formulation and development context (general, non-clinical):

• Role: BB‑Cl‑amidine–type molecules are used as discovery-stage chemical probes to explore target engagement, SAR, and exposure–response relationships in preclinical systems. They may inform medicinal chemistry campaigns but are not provided in a GMP or pharmacopoeial grade.
• Excipients/vehicles for research formulations: DMSO or PEG-containing vehicles (e.g., PEG400/saline with low DMSO content) are sometimes used for exploratory in vivo research; compatibility and tolerability must be established under institutional approvals. No specific formulation is provided for this catalog item.
• Regulatory status: No pharmacopeial monograph or clinical-grade designation. Researchers are responsible for ensuring appropriate approvals and SOPs for any nonclinical in vivo use.

For any application approaching regulated development, obtain GMP-grade material with full regulatory-support documentation; this Moligand™ product is not intended for that purpose.

Physical Properties

Item-specific measured properties:

• 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 (MP): Not specified for this item; refer to CoA/Spec Sheet.
• Boiling point (BP): Not applicable; compound is typically a nonvolatile solid (literature expectation for peptidic amidines).
• Density: Not specified for this item; refer to CoA/Spec Sheet.
• Refractive index: Not applicable to solids; refer to CoA/Spec Sheet if provided.
• UV/Vis cutoff or extinction: Not specified for this item; refer to CoA/Spec Sheet.

General/literature handling and solubility guidance (not item specifications):

• Solubility: Haloacetamidine PAD inhibitors are generally soluble in polar aprotic solvents such as DMSO and DMF and can be diluted into aqueous buffers with cosolvent. Aqueous solubility is enhanced by protonation of the amidine but may be limited at neutral pH without cosolvent.
• Ionization: Amidine functional groups are strongly basic (literature pKa of simple amidines ~11–13); many BB‑Cl‑amidine analogs are predominantly protonated under physiological conditions.
• Hygroscopicity: Multi-heteroatom, salt-forming molecules can be moderately hygroscopic; minimize atmospheric exposure.

Always verify exact physical constants and reconstitution behavior for this specific SKU from the product CoA prior to experimental planning.

Quality and Grades

• Grade/Purity: Moligand™ (as provided). This denotes Aladdin Scientific’s research-use small-molecule ligand/probe line intended for biochemical and chemical biology applications. It indicates a focus on identity confirmation and chromatographic purity appropriate for discovery research.
• What it does not imply: Unless explicitly stated on the CoA/Spec Sheet, Moligand™ is not a pharmacopoeial grade and carries no guaranteed limits for metals, residual solvents, water, nonvolatile residue, UV cutoff, or bioburden.

What to expect and how to use this grade effectively:

• Documentation: Refer to the lot-specific CoA for definitive purity assay (e.g., HPLC/LC–MS), identity confirmation (NMR/MS), and any residual solvent/water information if tested. If a numerical purity is not listed for your lot, treat as research grade and verify fitness-for-use via your in‑house QC.
• Recommended QC on receipt (good practice for covalent probes):
  • Quick LC–MS for molecular ion and major impurities.
  • Short HPLC purity check under your assay conditions (particularly for PAD activity assays where trace nucleophiles can quench inhibitors).
  • Optional: Titration of active concentration via target-based activity readout.
• Stabilizers: None are specified for this item; if stabilizers are present, they will appear on the CoA/Spec Sheet. Do not assume added antioxidants, scavengers, or salt forms.

For rigorous quantitative biology, consider orthogonal purity assessment (qNMR or calibrated LC) prior to potency benchmarking.

Reaction and Applications

This product is primarily a biochemical probe rather than a general-purpose synthetic reagent.

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

• Chemical biology of citrullination: Haloacetamidine inhibitors such as BB‑Cl‑amidine are widely used as covalent, mechanism-based tools to interrogate peptidyl arginine deiminase (PAD) enzyme function and to modulate protein citrullination in cells and lysates.
• Enzymology workflows:
  • In vitro PAD activity assays for IC50/Ki determination.
  • Time-dependent inhibition and reversibility studies to confirm covalent mechanism.
  • Competition assays with activity-based probes to quantify target engagement.
• Proteomics:
  • Target engagement profiling via ABPP (activity-based protein profiling) using fluorophore/biotin-tagged analogs; BB‑Cl‑amidine can serve as a competitor to map selectivity.
• Cell biology:
  • Modulation of PAD-dependent signaling; pathway validation using chemical inhibition.

Practical tips (general):

• Prepare fresh DMSO stocks and store aliquots at low temperature, anoxic, and desiccated conditions to preserve electrophile integrity.
• Filter sterilize through 0.22 μm PTFE/nylon when needed; avoid cellulose acetate in DMSO.
• Include vehicle controls and, where possible, inactive analog controls to confirm on-target effects.
• Avoid high concentrations of free thiols (e.g., DTT, βME) in assay buffers which can attenuate inhibitor potency via scavenging.

Reaction Conditions

This catalog item is not typically used as a reagent in chemical transformations, so standard “reaction conditions” are not generally applicable.

Experimental conditions for biological assays (general, literature-based; not item-specific):

• Stock solutions: Commonly prepared in dry DMSO at 10–50 mM, stored in aliquots to minimize freeze–thaw and moisture exposure.
• Enzyme assays: Performed in HEPES or Tris buffers near neutral pH with Ca2+ as required for PAD activity. Final DMSO typically maintained at ≤1–2% v/v. Incubation times vary from minutes to hours depending on kinetics and readout.
• Cell treatments: Concentration ranges and exposure times are model-dependent; begin with literature precedents for BB‑series PAD inhibitors and perform titrations with vehicle controls.
• Stability: Avoid extended preincubation in aqueous buffer without protein present; prepare fresh working solutions immediately before dosing to limit hydrolysis of electrophilic moieties.

For chemical synthesis conditions or coupling protocols, this product is not recommended; select appropriate reagents from synthetic catalogs instead.

Safety and Handling

GHS and hazard classification:

• 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 safety guidance for haloacetamidine/alkylating research reagents (literature-based; not item-specific):

• Potential hazards: Many chloroacetamidine-containing molecules are electrophilic and can alkylate nucleophiles (e.g., thiols). Treat as potentially harmful if swallowed, inhaled, or upon skin/eye contact. Avoid generating aerosols or dust.
• Engineering controls: Handle in a certified chemical fume hood with local exhaust ventilation.
• PPE: Lab coat, safety glasses or face shield, and appropriate chemically resistant gloves (e.g., disposable nitrile). Change gloves frequently when handling DMSO solutions due to enhanced dermal transport.
• Incompatibilities: Avoid strong nucleophiles and bases that may cause decomposition or undesired substitution; segregate from strong oxidizers. Moisture can promote hydrolysis.
• First aid (overview; defer to SDS):
  • Skin/eye contact: Immediately flush with water for ≥15 min and remove contaminated clothing; seek medical attention.
  • Inhalation: Move to fresh air; monitor breathing; obtain medical attention.
  • Ingestion: Rinse mouth; do not induce vomiting; seek medical attention.
• Waste: Collect solutions and contaminated disposables as halogenated organic waste or per institutional hazardous-waste procedures.

Always consult the product’s SDS for authoritative hazard, exposure limits, and response measures.

Solvent Selection

Applicability: BB‑Cl‑Amidine is a small-molecule probe typically handled as a solid and dispensed as concentrated stock solutions. Solvent choice impacts stability, assay compatibility, and delivery.

General/literature guidance (not item-specific):

• Primary stock solvents:
  • DMSO: Preferred for high-concentration stocks; excellent solubilizing power for cationic amidines; miscible with water for buffer dilution.
  • DMF: Useful alternative when DMSO is incompatible; also good solvent for amidines.
• Aqueous media:
  • Amidine basicity favors protonation and some water compatibility; however, many analogs exhibit limited aqueous solubility at neutral pH without cosolvent. Use 0.1–1% DMSO as a vehicle when preparing assay buffers.
• Stability considerations:
  • Avoid prolonged exposure to strong nucleophiles (e.g., high thiol concentrations) that can consume haloacetamidine warheads.
  • Minimize water and base to limit hydrolysis or elimination.
• Choosing among vehicles:
  • For enzyme assays (e.g., PAD activity), DMSO at low final percentages (≤1–2%) is commonly tolerated; confirm assay tolerance.
  • For cell-based studies, prefilter 0.22 μm and keep final DMSO ≤0.1–0.5% if possible; confirm with your cell model.

Comparison snapshot (general):

• DMSO: Highest solubility; may enhance dermal transport—use care.
• DMF: Similar solvation; higher volatility/odor; ensure compatibility.
• Aqueous buffers: Best biocompatibility; may require cosolvent or pH adjustment.

Storage and Reconstitution

Item-specific conditions (as provided for this SKU):

• Storage Conditions: Store at −20 °C, Argon charged.
• Shipped In: Ice chest + Ice pads.

Additional item-specific notes:

• Appearance: Not specified for this item; refer to CoA/Spec Sheet.
• Stabilizers/Salts: Not specified for this item; refer to CoA/Spec Sheet.

General guidance (not item-specific specifications):

• Containerization: Keep tightly sealed in a dry, inert atmosphere (argon or nitrogen). Use a desiccant and protect from light if the CoA or literature suggests photosensitivity.
• Reconstitution: If not otherwise instructed on the CoA, dissolve in anhydrous DMSO to prepare a concentrated stock. Filter through 0.22 μm if sterile solutions are required. Record the exact concentration by weight and adjust for purity if provided on the CoA.
• Aliquoting: Prepare single-use aliquots to minimize freeze–thaw cycles and headspace oxygen/moisture exposure.
• Working solutions: Prepare immediately before use; avoid extended standing in aqueous buffer to limit hydrolysis of electrophilic moieties.
• Stability checks: For critical experiments, verify integrity by LC–MS after storage.

Always consult the lot-specific CoA/SDS for definitive instructions on storage, handling, and reconstitution.

Structure and Identity

BB-Cl-Amidine is a small-molecule research reagent commonly used as a covalent haloacetamidine-type probe in chemical biology studies.

• SKU: B1021758
• Product Name: BB-Cl-Amidine
• CAS: 1802637-39-3 (as provided)
• CID: 129021946 (as provided)
• InChIKey: 434482 (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.

Structural features (general/literature description):

• Literature describes BB‑Cl‑amidine analogs as peptide- or amino acid–derived haloacetamidines that function as electrophilic warheads targeting active-site cysteine/nucleophiles in peptidyl arginine deiminases (PADs). They typically comprise:
  • An amidine/imidamide moiety (strongly basic) capable of engaging acidic active-site residues.
  • A haloacetamidine or related chloroacetamidine electrophile for irreversible covalent capture.
  • An N-acyl/N-aryl cap (e.g., benzoyl/benzyl variants) modulating potency and cell permeability.

2D structure in words (general/literature):

• A central amino acid–like scaffold bearing an N-acylated side chain; terminal chloroacetamidine electrophile; additional amide linkages; multiple hydrogen-bond donors/acceptors; overall cationic tendency at physiological pH due to amidine basicity.

Note: Exact atom connectivity, stereochemistry, and substituent pattern for this catalog item are not specified here; consult the Certificate of Analysis (CoA) and structure file on the product page for definitive identity.

Synthetic Utility

Not a general-purpose synthetic building block in routine organic synthesis. Its primary value is as a ready-to-use biochemical probe.

General chemistry perspective (literature-based):

• Functional groups expected in BB‑Cl‑amidine analogs include amidines and haloacetamidines (electrophilic), amides, and possibly protected amino acid–derived motifs. These groups are sensitive to strong base and nucleophiles.
• Derivatization: Researchers sometimes prepare tagged derivatives (e.g., alkyne-, fluorophore-, or biotin-labeled analogs) for activity-based protein profiling and pull-down assays. Such work typically starts from related intermediates rather than modifying the final inhibitor.
• Stability constraints: The chloroacetamidine warhead can undergo substitution or hydrolysis; therefore, late-stage functionalization is limited. Protecting-group strategies and low-temperature conditions are often required during synthesis.

If you require a synthetic intermediate or a functionalized analog for conjugation, contact technical support for custom synthesis options rather than modifying this final probe in-house.

Target Specificity

Only item-specific data may be included here.

• Specific target(s), isoform selectivity, Kd/IC50 values, clone/isotype (if antibody), or species reactivity: Not specified for this item; refer to CoA/Spec Sheet and primary literature for BB‑Cl‑amidine probes.

Note: While the literature discusses BB‑Cl‑amidine analogs as covalent PAD inhibitors, no target-specific performance data are provided for this specific SKU. Users should confirm target engagement and selectivity in their own system.