Tinostamustine - ≥98% , CAS No.1236199-60-2

CAS: 1236199-60-2 Cat. No.: T414166 Formule: C₁₉H₂₈Cl₂N₄O₂ Poids moléculaire: 415.36 Numéro CE: 985-846-7 PubChem CID: 46836227

QUALITÉ & PURETÉ ≥98%

Synonyms

7-(5-(bis(2-chloroethyl)amino)-1-methyl-1H-benzo[d]imidazol-2-yl)-N-hydroxyheptanamide | 1236199-60-2 | 1H-Benzimidazole-2-heptanamide, 5-(bis(2-chloroethyl)amino)-N-hydroxy-1-methyl- | DB15147 | UNII-29DKI2H2NY | 7-{5-[Bis(2-chloroethyl)amino]-1-methyl-1

Storage

Store at -20°C

Shipped In

Ice chest + Ice pads

Vue d’ensemble

Information

Tinostamustine(EDO-S101) is a first-in-classalkylating deacetylaseinhibitor with IC50 values of 9 nM, 9 nM, 25 nM and 107 nM for HDAC1, HDAC2, HDAC3 and HDAC8 (Class 1 HDACs) respectively and 6 nM, 72 nM for HDAC6 and HDAC10 (Class II HDACs).

Targets

HDAC6 (Cell-free assay); HDAC1 (Cell-free assay); HDAC2 (Cell-free assay); HDAC3 (Cell-free assay); HDAC10 (Cell-free assay) 31723,6 nM; 9 nM; 9 nM; 25 nM; 72 nM

In vitro

The IC50s of EDO-S101 range between 5-13 μM in 8 myeloma cell lines. EDO-S101 has significant synergistic cytotoxicity with the proteasome inhibitors bortezomib and carfilzomib across all cell types tested. EDO-S101 induces strong protein and histone acetylation and is a strong inducer of pIRE-1, the key activator protein of the UPR in MM cells.

Cell Research(from reference)

Cell lines：HL-60 cells 

Concentrations：4 μM 

Incubation Time：0, 6, 12, 18, 24h 

Spécifications

Synonymes

7-(5-(bis(2-chloroethyl)amino)-1-methyl-1H-benzo[d]imidazol-2-yl)-N-hydroxyheptanamide | 1236199-60-2 | 1H-Benzimidazole-2-heptanamide, 5-(bis(2-chloroethyl)amino)-N-hydroxy-1-methyl- | DB15147 | UNII-29DKI2H2NY | 7-{5-[Bis(2-chloroethyl)amino]-1-methyl-1

Spécifications et pureté

≥98%

Mécanismes biochimiques et physiologiques

Tinostamustine(EDO-S101) is a first-in-class alkylating deacetylase inhibitor with IC50 values of 9 nM, 9 nM, 25 nM and 107 nM for HDAC1, HDAC2, HDAC3 and HDAC8 (Class 1 HDACs) respectively and 6 nM, 72 nM for HDAC6 and HDAC10 (Class II HDACs).

Conditions de stockage de stockage

Store at -20°C

Expédié en

Ice chest + Ice pads

Ce produit nécessite l'expédition en chaîne froide. Les services terrestres et autres services économiques ne sont pas disponibles.

Pureté

≥98%

Propriétés du produit

ALogP

4.36

Nombre de HBD

1

Liaison rotative

12

Noms et identifiants

Pubchem Sid

488201369

Pubchem Sid Url

https://pubchem.ncbi.nlm.nih.gov/substance/488201369

Sourires canoniques

CN1C2=C(C=C(C=C2)N(CCCl)CCCl)N=C1CCCCCCC(=O)NO

IUPAC Name

7-[5-[bis(2-chloroethyl)amino]-1-methylbenzimidazol-2-yl]-N-hydroxyheptanamide

InChIKey

GISXTRIGVCKQBX-UHFFFAOYSA-N

INCHI

1S/C19H28Cl2N4O2/c1-24-17-9-8-15(25(12-10-20)13-11-21)14-16(17)22-18(24)6-4-2-3-5-7-19(26)23-27/h8-9,14,27H,2-7,10-13H2,1H3,(H,23,26)

Isomères SMILES

CN1C2=C(C=C(C=C2)N(CCCl)CCCl)N=C1CCCCCCC(=O)NO

PubChem CID

46836227

Poids moléculaire

415.36

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Organoheterocyclic compounds
    • Classe Benzimidazoles

• Kingdom: Organic compounds
• Superclass: Organoheterocyclic compounds
• Classe: Benzimidazoles
• Subclass: Not available
• Intermediate Tree Nodes: Not available
• Direct Parent: Benzimidazoles
• Alternative Parents: Nitrogen mustard compounds Dialkylarylamines N-substituted imidazoles Benzenoids Heteroaromatic compounds Hydroxamic acids Amino acids and derivatives Azacyclic compounds Organopnictogen compounds Organochlorides Organic oxides Hydrocarbon derivatives Carbonyl compounds Alkyl chlorides
• Molecular Framework: Aromatic heteropolycyclic compounds
• Substituents: Benzimidazole - Dialkylarylamine - Tertiary aliphatic/aromatic amine - Nitrogen mustard - Benzenoid - N-substituted imidazole - Heteroaromatic compound - Imidazole - Azole - Tertiary amine - Hydroxamic acid - Amino acid or derivatives - Azacycle - Carboxylic acid derivative - Organic nitrogen compound - Organic oxygen compound - Organopnictogen compound - Organic oxide - Hydrocarbon derivative - Organooxygen compound - Organonitrogen compound - Organochloride - Organohalogen compound - Carbonyl group - Amine - Alkyl halide - Alkyl chloride - Aromatic heteropolycyclic compound
• Description: This compound belongs to the class of organic compounds known as benzimidazoles. These are organic compounds containing a benzene ring fused to an imidazole ring (five member ring containing a nitrogen atom, 4 carbon atoms, and two double bonds).
• 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

Cibles associées (humaines)

NB-4 (999 Activities)

Explore this target

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

Panel NCI-60 (60 carcinoma cell lines) (1088 Activities)

Explore this target

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

Kasumi 1 (420 Activities)

Explore this target

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

Cibles associées (non humaines)

Hdac1 Histone deacetylase 1 (93 Activities)

Discover Target: Hdac1

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

Mécanismes d'action

Propriétés chimiques et physiques

• Solubilité: Solubility (25°C) In vitro DMSO: 14 mg/mL (33.7 mM); Ethanol: 2 mg/mL (4.81 mM); Water: Insoluble
• DMSO (mg/mL) Solubilité maximale: 14
• DMSO (mM) Solubilité maximale: 33.7057010785824
• Eau (mg/mL) Solubilité maximale: ＜1
• Poids moléculaire: 415.400 g/mol
• XLogP3: 3.600
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 4
• Rotatable Bond Count: 12
• Exact Mass: 414.159 Da
• Monoisotopic Mass: 414.159 Da
• Topological Polar Surface Area: 70.400 Ų
• Heavy Atom Count: 27
• Formal Charge: 0
• Complexity: 438.000
• Isotope Atom Count: 0
• Defined Atom Stereocenter Count: 0
• 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 validated applications, recommended dilutions, and controls: Not specified for this item; refer to CoA/Spec Sheet or internal SOPs.

• General workflow suggestions (literature/general)

  • Cell-based HDAC/DNA-damage studies:
    • Prepare fresh DMSO stock; treat cells with a dose range and include DMSO vehicle control.
    • Readouts: histone acetylation (WB/ELISA), γH2AX foci (IF), cell-cycle profiling (flow cytometry), viability (ATP or resazurin assays).
  • Biochemical HDAC assays:
    • Use fluorogenic or MS-based deacetylase assays to gauge HDAC inhibition; include zinc chelator controls to benchmark hydroxamate behavior.
  • Omics profiling:
    • RNA-seq or proteomics after defined exposures to map pathway responses; include time-course for dynamics.

These are non-validated, literature-style outlines. Optimize conditions for your platform and consult institutional guidelines.

Biological Roles

• Nature of the compound (literature/general)

  • Tinostamustine is a bifunctional small molecule combining a histone deacetylase (HDAC) inhibitory hydroxamate with a nitrogen mustard DNA-alkylating moiety.

• Roles in cellular studies (literature/general)

  • Chromatin modulation: Inhibition of HDACs increases histone acetylation, promoting a more open chromatin state; used to probe transcriptional regulation and chromatin accessibility.
  • DNA damage induction: Alkylation can lead to interstrand crosslinks and other lesions, enabling interrogation of DNA damage response pathways (e.g., ATR/ATM signaling, Fanconi anemia pathway).
  • Synthetic lethality exploration: By coupling chromatin effects with DNA lesions, researchers study vulnerabilities in DNA repair–deficient cell systems.
  • Cell-cycle effects: Often associated with S/G2 checkpoint activation in response to induced damage (context-dependent; verify in your model).

• Selectivity considerations (literature/general)

  • Hydroxamate-based HDAC ligands are typically pan-HDAC with varying potency across isoforms; exact isoform profile for tinostamustine should be obtained from primary literature and is not specified for this item.

All statements above describe research/biochemical utility only. No clinical or medical claims are made. Consult primary literature for quantitative potency and isoform data.

Buffer Applications

This compound is a small-molecule research tool and does not function as a buffering agent.

• Practical handling in buffers (literature/general)
  • Prepare concentrated DMSO stocks, then dilute into biological buffers (e.g., PBS, HBSS, culture media) ensuring the final DMSO percentage is compatible with the system.
  • If precipitation occurs upon dilution, consider adding the stock slowly with vigorous mixing, warming gently to ambient temperature, or using minimal cosolvent-compatible surfactant.
  • Avoid strongly basic buffers that may promote hydroxamate hydrolysis or mustard degradation.

No defined pKa-based buffer systems are applicable to this item.

Green Alternatives

This product is a targeted research compound rather than a process solvent or commodity reagent. “Green alternatives” are therefore more about handling media and vehicles than replacing the compound itself.

• Greener solvent choices for stock/assay preparation (literature/general)

  • Prefer water-compatible systems with minimal DMSO where possible; evaluate cyclodextrin inclusion or low levels of approved surfactants to reduce organic cosolvent.
  • If organic cosolvent is required, DMSO remains widely accepted for in vitro work; small amounts of ethanol may be acceptable in some assays. Avoid high volumes of DMF/DMAC due to toxicity and environmental profiles.

• Operational green chemistry practices

  • Microscale experimentation to minimize cytotoxic waste.
  • Closed handling (vials with septa) to limit exposure and volatilization.
  • Waste segregation for cytotoxic/alkylating agents; consider on-site neutralization only if validated by EHS.

Comparison (general)

• Direct substitution of tinostamustine with a “green alternative” is not applicable, as its dual-function mechanism is unique to the research question. Optimize solvents and workflows around it to reduce environmental and exposure impact.

Pharmaceutical Uses

No therapeutic, diagnostic, or clinical claims are made for this product. It is supplied strictly for research use only.

• Formulation context in research (literature/general)

  • For in vitro work, small volumes of DMSO stock are commonly diluted into assay media.
  • For in vivo research (if permitted by local regulations), co-solvent systems such as DMSO:PEG400:saline or Captisol-based vehicles are sometimes explored; exact compositions must be developed and validated by the user and are not specified for this item.
  • Endotoxin/sterility are not implied for small-molecule solids unless explicitly stated in accompanying documentation.

• Pharmacopeial status

  • No pharmacopeial monograph is implied. Any use in regulated settings requires independent qualification and validation.

Physical Properties

• Item-specific specs (from Product Data)

  • Appearance: Not specified for this item; refer to CoA/Spec Sheet.
  • Molecular Weight: Not specified for this item; refer to CoA/Spec Sheet.
  • Melting/Boiling Point, Density, Refractive Index, UV cutoff: Not specified for this item; refer to CoA/Spec Sheet.
  • Solubility: Not specified for this item; refer to CoA/Spec Sheet.

• Literature/general expectations (for planning only; confirm experimentally)

  • Physical state: Typically handled as a solid in small-molecule libraries.
  • Solubility strategy: Frequently prepared as concentrated DMSO stocks (e.g., millimolar range) and diluted into aqueous assay buffers with cosolvent; actual limits depend on batch/form and counterions.
  • pKa behavior: Hydroxamic acids (general) pKa ~8–9 (literature, class-wide); tertiary amines often have pKaH ~7–10 (class-wide). Exact values for this item are not specified.
  • Partitioning: Amphiphilic due to both polar (hydroxamate/amide) and lipophilic (aryl/mustard) regions; expect moderate protein binding and limited aqueous solubility without cosolvent—verify experimentally.

Note: Use these literature/general notes only for preliminary planning. For specifications required in regulated or quantitative work, consult the item’s CoA/Spec Sheet and SDS.

Quality and Grades

• Item-specific grade/purity (from Product Data)

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

• Interpreting common grades (general guidance)

  • Screening/Library grade: Suitable for biochemical/cellular assays; often accompanied by NMR/LC-MS identity and purity data (e.g., HPLC area%).
  • Analytical/Reagent grades: Emphasize low inorganic/organic impurities; may not be relevant for bioactivity screening unless accompanied by bioassay-grade documentation.
  • Stabilizers/Counterions: Hydroxamate-containing compounds are sometimes provided as free acids/bases or salts; counterion and water content can influence solubility and assay performance.

• Practical recommendations

  • Request the CoA for exact purity (HPLC), residual solvents, and salt form.
  • Verify identity/purity on receipt (e.g., LC–MS, 1H NMR) before critical studies.
  • If used in quantitative biology, confirm endotoxin/bioburden only if relevant to your application; not typically provided for small molecules unless specified.

Reaction and Applications

• Applicability as a reagent

  • Tinostamustine is a specialized bioactive probe and is not commonly used as a general-purpose synthetic reagent. It is principally applied in chemical biology and phenotypic screening.

• Research applications (literature/general)

  • Epigenetics/Chromatin studies: Hydroxamic-acid motif engages HDACs; used to explore histone acetylation dynamics.
  • DNA damage/repair research: Nitrogen-mustard moiety forms DNA adducts; applied in assays of DNA damage response (DDR), checkpoint activation, and repair pathway dependencies.
  • Combination mechanism studies: Serves as a tool compound to evaluate synergy between chromatin relaxation (HDAC inhibition) and DNA alkylation within a single molecule.
  • Omics profiling: Employed in transcriptomic/proteomic studies to map global responses to dual HDAC inhibition and alkylation stress.

• Practical notes

  • Prepare fresh working solutions to limit time-dependent degradation of mustard and hydroxamate functionalities.
  • Control for solvent vehicle effects and include appropriate comparators (e.g., a pure HDAC inhibitor and a pure alkylator) to deconvolute mechanisms.
  • Use light-protective handling if photolability is suspected; limit exposure to moisture and elevated temperature during assays.

For synthetic transformations or building-block applications, this molecule is not typically selected; see the Synthetic Utility section for context.

Reaction Conditions

This product is a bioactive probe rather than a synthetic reagent; standard “reaction conditions” are not typically applicable.

• Handling/assay conditions (literature/general)
  • Stock solutions: Prepare in anhydrous DMSO at a concentration suitable for your assay; aliquot and store at −20 °C to minimize freeze–thaw.
  • Working concentrations: Determined empirically per model system. Include vehicle controls and, where relevant, comparator compounds (HDAC inhibitor alone; alkylator alone).
  • Incubation parameters: Time- and dose-dependence should be profiled; monitor endpoints such as histone acetylation (e.g., H3/H4 Ac by Western blot) and DNA damage markers (e.g., γH2AX).
  • Stability: Avoid prolonged exposure to moisture and elevated temperature which can promote hydroxamate hydrolysis and mustard decomposition.

All quantitative conditions (concentrations, exposure times) must be derived from primary literature or pilot experiments; they are not specified for this item.

Safety and Handling

• Item-specific hazard data (from Product Data)

  • Signal Word / H-Statements / GHS Classification / Pictograms: Not specified for this item; refer to SDS.

• General safety guidance (literature/general for alkylating/HDAC-inhibiting research chemicals)

  • Hazard profile: Nitrogen mustards are potent alkylating agents; hydroxamic acids can chelate metals. Expect potential for acute toxicity, skin/eye irritation, respiratory irritation, and mutagenicity. Handle as a cytotoxic research chemical.
  • Controls/PPE: Work in a certified chemical fume hood or ventilated enclosure. Wear lab coat, double nitrile gloves (change regularly), safety glasses or face shield for splash risk. Use dedicated cytotoxic waste containers.
  • Incompatibilities: Avoid strong bases/acids that may degrade hydroxamates; avoid reactive nucleophiles and strong oxidizers. Protect from moisture for stability where applicable.
  • Spill/Exposure (overview): For small spills, absorb with inert material while wearing appropriate PPE; dispose as hazardous cytotoxic waste. Skin/eye contact: immediate decontamination with copious water for ≥15 min; seek medical attention. Ingestion/inhalation: seek medical attention; provide SDS to responders.
  • Decontamination: Use appropriate deactivating/oxidizing agents only if validated; otherwise, physical containment and disposal are preferred for alkylators.

Always defer to the current SDS and institutional cytotoxic handling procedures for authoritative guidance.

Solvent Selection

• Item-specific solubility data: Not specified for this item; refer to CoA/Spec Sheet.

• Literature/general guidance for tinostamustine and similar amphiphilic bioactives

  • Stock preparation: DMSO is commonly used due to broad solvency and assay compatibility. Prepare concentrated stocks and dilute into aqueous buffers with final DMSO typically ≤0.1–0.5% v/v for cell-based assays (verify tolerance).
  • Alternative solvents: DMF and ethanol can dissolve many hydroxamate/mustard hybrids; cosolvent systems (e.g., DMSO:water, DMSO:PBS, or DMSO:PEG400:saline) may be employed depending on assay.
  • Aqueous buffers: Limited inherent aqueous solubility is expected; surfactants (e.g., 0.01–0.1% Tween-80) or complexation (cyclodextrins) can aid dissolution, subject to assay constraints.
  • pH effects: Hydroxamate deprotonation and amine protonation can alter solubility; avoid high pH that can hydrolyze hydroxamates and conditions that promote mustard decomposition.

• Practical tips

  • Filter-sterilize final working solutions (0.22 µm) when used in cell culture.
  • Minimize freeze–thaw of DMSO stocks; aliquot upon first dissolution.
  • Confirm absence of precipitation after dilution into assay media (visual check, nephelometry).

All solvent choices should be validated in pilot experiments for the specific biological system.

Storage and Reconstitution

• Item-specific instructions (from Product Data)

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

• Reconstitution (general guidance)

  • Use anhydrous, oxygen- and moisture-minimized conditions when first opening the container.
  • Dissolve in high-purity DMSO to prepare a concentrated stock; mix gently until fully dissolved. Exact solubility and concentration limits are not specified for this item; refer to CoA/Spec Sheet and verify experimentally.
  • Filter if particulate is observed (PTFE, 0.22 µm) and aliquot into amber vials to avoid repeated freeze–thaw and potential light sensitivity.

• Handling and stability (general)

  • Store aliquots at −20 °C, tightly sealed, desiccated, and protected from light. Avoid multiple freeze–thaw cycles.
  • For aqueous working solutions, prepare fresh just prior to use; discard unused portions according to cytotoxic waste procedures.

Always consult the product’s CoA and SDS for definitive storage stability, re-test intervals, and any specific cautions for this lot.

Structure and Identity

A bifunctional small molecule combining a DNA-alkylating nitrogen mustard and a hydroxamic-acid HDAC inhibitor pharmacophore (commonly referenced in the literature as EDO-S101).

• Item-specific identifiers (from Product Data)

  • Product Name: Tinostamustine
  • SKU: T414166
  • CAS: 1236199-60-2
  • CID: 46836227
  • InChIKey: 103143 (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 (literature/general)

  • Functional groups: hydroxamic acid (Zn2+-chelating HDAC-binding motif), di(2-chloroethyl)amino mustard (alkylator), amide/urea-like linkages, aromatic linkers.
  • Bifunctional design: enables chromatin modulation (HDAC inhibition) concurrent with DNA alkylation.
  • Ionization: hydroxamate can be deprotonated under basic conditions; tertiary amine may be protonated under acidic conditions.

• 2D structure description (literature/general)

  • An aromatic core bearing a tether to a terminal hydroxamate; a separate pendant tertiary amino nitrogen substituted with two 2-chloroethyl arms (mustard). The architecture provides a polar chelating terminus (hydroxamate) and a lipophilic/alkylating terminus (mustard) joined through amide/aryl linkers.

Synthetic Utility

Tinostamustine itself is not typically used as a synthetic intermediate; it is a finalized, functionally complex probe molecule. Nonetheless, understanding its functionality informs derivatization and analogue synthesis (literature/general):

• Reactive motifs and implications

  • Hydroxamic acid: amenable to O-acylation, metal chelation, and potential hydrolysis to corresponding acids/amides under forcing conditions.
  • Nitrogen mustard (bis(2-chloroethyl)amino): intramolecular aziridinium formation under physiological/basic conditions enables alkylation of nucleophiles (e.g., DNA bases); this reactivity limits many downstream chemical manipulations on the intact molecule.
  • Amide/aryl linkers: provide sites for analogue development via amide coupling, Suzuki/Heck cross-couplings in precursor scaffolds (not typically on the final mustard-bearing molecule due to instability).

• Retrosynthetic considerations

  • Convergent assembly from a protected HDAC-ligand fragment (hydroxamate introduced late-stage) and a mustard-bearing amine fragment (installed under carefully controlled, dry conditions to avoid premature decomposition).

• Derivatization strategies

  • Prodrug or masked hydroxamate approaches (e.g., O-alkyl hydroxamates) are explored in literature to tune PK/stability; any modifications should be validated for retained dual-function behavior.

For routine synthesis tasks, choose simpler building blocks; employ tinostamustine primarily as a research probe.

Target Specificity

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

• Literature/general context

  • Designed to engage HDAC enzymes via hydroxamate chelation of the catalytic Zn2+ while independently delivering DNA-alkylating activity through a nitrogen mustard. Isoform-level HDAC specificity, potency values (IC50/Ki), and cellular target engagement are model- and study-dependent and are not specified here.

Users should consult peer-reviewed studies for quantitative target profiles relevant to their system.