Product Manager: Selina Zhang; Email: selina@coreychem.com
| Product Name | BenzeneDiaMidoEthaneThiol N,N’-Bis(2-Mercaptoethyl)isophthalaMide |
| Synonyms | Emeramide(BDTH2);1,3-(N-MERCAPTOETHYLCARBOXAMIDE)BENZENE,99%BDET;BenzeneDiaMidoEthaneThiolN,N’-Bis(2-Mercaptoethyl)isophtChemicalbookhalaMide;Emeramide;N,N’-Bis(2-mercaptoethyl)isophthalamide;NBMI;BDTH2;1,3-Benzenedicarboxamide,N1,N3-bis(2-mercaptoethyl)- |
| CAS NO | 351994-94-0 |
| Purity |
99% |
| Appearance |
White solid |
| MF | C12H16N2O2S2 |
| MW | 284.4 |
| Contact | selina@coreychem.com |
(1S,2S)-2-Fluoro-N-[6-(4-methyl-3-pyridinyl)-2-benzothiazolyl]cyclopropanecarboxamide (CAS: 2304918-81-6) is a highly potent, selective, and orally bioavailable small-molecule kinase inhibitor, widely used in targeted cancer therapy, immuno-oncology, and precision medicine research. Featuring a unique molecular architecture that combines a conformationally rigid fluorinated cyclopropane carboxamide with a benzothiazole-pyridine biaryl scaffold, it offers enhanced binding affinity, superior selectivity over off-target kinases, and improved metabolic stability compared to conventional flat heterocyclic inhibitors. Its well-defined stereochemistry, reliable synthetic accessibility, and established utility as a tool for probing oncogenic signaling pathways make it a dependable standard for drug discovery, chemical biology, and molecular pharmacology research. Its primary applications are outlined below:
1. Medicinal Chemistry & Drug Discovery
Targeted Kinase Inhibition (e.g., GSK-3β, RIPK1, or related therapeutic targets)
This compound serves as a lead candidate for the development of selective inhibitors targeting disease-relevant kinases such as glycogen synthase kinase-3 beta (GSK-3β), receptor-interacting serine/threonine-protein kinase 1 (RIPK1), or other emerging oncogenic and neuroinflammatory kinases. The fluorinated cyclopropane moiety enhances conformational pre-organization for optimal binding to the kinase hinge region, while the benzothiazole-pyridine scaffold engages in critical π–π stacking and hydrogen-bonding interactions. Medicinal chemists employ this scaffold in extensive SAR studies to fine-tune potency, selectivity, and physicochemical properties.
Oncology Therapeutics Development
The compound and its analogues are evaluated as antiproliferative agents against various cancer cell lines, including colorectal, pancreatic, breast, and hematological malignancies. By modulating key signaling nodes (e.g., Wnt/β-catenin, NF-κB, or apoptosis pathways), it can induce cell cycle arrest, promote apoptosis, and synergize with standard chemotherapeutics. Researchers utilize this scaffold in preclinical efficacy studies, combination therapy regimens, and patient-derived xenograft (PDX) models to assess translational potential.
Neurodegenerative & Neuroinflammatory Disease Research
Given its ability to modulate kinases implicated in neuroinflammation and neuronal survival, the compound is investigated for therapeutic applications in Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, and traumatic brain injury. The favorable brain penetration profile, conferred by the lipophilic fluorinated cyclopropane and rigid aromatic system, supports its evaluation in CNS disease models.
Immuno-Oncology & Inflammatory Disorders
The compound is explored as a modulator of innate immune signaling pathways, including necroptosis and pyroptosis, via inhibition of RIPK1 or related kinases. Researchers assess its effects on cytokine production, immune cell infiltration, and tumor immune microenvironment remodeling, supporting its development as a novel immunomodulatory agent for cancer and chronic inflammatory diseases.
2. Chemical Biology & Chemical Probe Development
Selective Kinase Probe
As a highly selective ATP-competitive kinase inhibitor, this compound serves as a valuable chemical probe for dissecting kinase-dependent signaling networks in cellular and in vivo systems. Its well-characterized binding mode, selectivity profile, and cellular activity make it an indispensable tool for target validation, pathway mapping, and phenotypic screening.
Clickable & Photoaffinity Probe Derivatives
Medicinal chemists and chemical biologists modify the compound at suitable positions (e.g., the methyl group on pyridine or the benzothiazole ring) to introduce clickable handles (azides, alkynes) or photoaffinity labels (diazirines, benzophenones). These derivatives enable pull-down assays, target identification, and proteome-wide profiling of kinase–ligand interactions.
Activity-Based Protein Profiling (ABPP)
The scaffold is employed in competitive ABPP workflows to assess kinase engagement and occupancy in complex biological matrices. Its high affinity and selectivity allow researchers to quantify target engagement, evaluate off-target liabilities, and prioritize lead compounds in drug discovery campaigns.
3. Biochemical Research & Enzyme Studies
Kinase Selectivity & Inhibition Kinetics
The compound is widely utilized in kinase panel screening assays (e.g., Eurofins KinaseProfiler, KINOMEscan) to determine its selectivity profile across hundreds of human kinases. Researchers measure IC₅₀ values, binding kinetics (Kd, kon, koff), and mode of inhibition (ATP-competitive vs. allosteric) using biochemical assays such as ADP-Glo, HTRF, and surface plasmon resonance (SPR).
Binding Mode Elucidation via Structural Biology
Co-crystallization studies with target kinases (e.g., GSK-3β or RIPK1) provide high-resolution structural insights into the molecular determinants of binding affinity and selectivity. The fluorinated cyclopropane group often contributes to entropy-driven binding through desolvation effects and hydrophobic interactions, guiding rational drug design.
Cellular Signaling Pathway Dissection
Researchers use this compound to inhibit specific kinase activities in cell-based assays, followed by phosphoproteomic analysis (e.g., Western blotting, mass spectrometry) to map downstream signaling cascades. It is employed to study Wnt/β-catenin, PI3K/AKT, MAPK/ERK, and NF-κB pathways in various cellular contexts.
4. Pharmacology & ADME/Toxicology Studies
Pharmacokinetic (PK) Profiling
The compound is utilized as a model drug candidate in preclinical PK studies to evaluate oral bioavailability, plasma half-life, tissue distribution, and metabolic stability. Its fluorinated cyclopropane moiety often imparts reduced CYP450-mediated oxidation, improved metabolic half-life, and favorable drug-like properties. Researchers employ LC-MS/MS methods to quantify compound levels in plasma, brain, and target tissues.
Metabolite Identification & Stability Studies
Investigators study the in vitro and in vivo metabolic pathways of this compound using liver microsomes, hepatocytes, and recombinant CYP enzymes. Identification of major metabolites (e.g., oxidative defluorination, pyridine N-oxidation, or glucuronidation) informs medicinal chemistry efforts to block metabolic soft spots and improve systemic exposure.
Drug-Drug Interaction (DDI) Risk Assessment
The compound is evaluated for its potential to inhibit or induce cytochrome P450 isoforms (CYP1A2, CYP2C9, CYP2D6, CYP3A4) and transporters (P-gp, BCRP, OATP) to assess DDI liabilities. These studies are critical for advancing the compound toward clinical development.
Toxicological Profiling
In vitro safety pharmacology assays (hERG channel inhibition, Ames test, micronucleus assay) are performed to assess the compound’s safety profile. Its selectivity for the target kinase over off-targets reduces the risk of mechanism-based toxicities, supporting its continued development as a therapeutic candidate.
5. Neuroscience & CNS Drug Discovery
Blood-Brain Barrier (BBB) Permeability Studies
Due to its optimized lipophilicity (clogP), low molecular weight, and minimal P-gp efflux liability, the compound exhibits favorable BBB penetration. Researchers employ in vitro BBB models (e.g., hCMEC/D3 cell monolayers or parallel artificial membrane permeability assays, PAMPA-BBB) and in vivo brain distribution studies to assess CNS exposure.
Neuroprotection & Neuroinflammation Models
The compound is evaluated in preclinical models of ischemic stroke, spinal cord injury, and neuroinflammatory diseases. By inhibiting RIPK1 or GSK-3β, it reduces neuronal apoptosis, microglial activation, and pro-inflammatory cytokine release, providing therapeutic benefit in disease models.
Cognitive Function & Behavioral Studies
In rodent models of Alzheimer’s disease or aging-related cognitive decline, researchers assess the compound’s effects on learning, memory, and synaptic plasticity. Modulation of GSK-3β activity can impact tau phosphorylation and amyloid-β pathology, making it a candidate for disease-modifying strategies in dementia.
6. Immunology & Inflammation Research
Necroptosis & Pyroptosis Inhibition
The compound is employed as a tool to study programmed cell death pathways. Inhibition of RIPK1 prevents necroptotic cell death in models of ischemia-reperfusion injury, pancreatitis, and inflammatory bowel disease. Researchers investigate its effects on cell death, tissue damage, and inflammatory cytokine release (e.g., TNF-α, IL-1β, IL-6).
Macrophage & T-Cell Modulation
By targeting kinases involved in immune receptor signaling, the compound modulates macrophage polarization (M1/M2 balance) and T-cell activation. It is used in studies of autoimmune diseases (e.g., rheumatoid arthritis, psoriasis, multiple sclerosis) to evaluate its immunomodulatory potential.
Sepsis & Systemic Inflammation Models
In preclinical sepsis models, the compound is assessed for its ability to reduce systemic inflammation, improve survival rates, and preserve organ function. Its rapid oral absorption and favorable PK profile support its evaluation in acute inflammatory conditions.
7. Handling & Storage
Storage Conditions
Store as supplied in tightly sealed, amber glass vials under inert atmosphere (N₂ or Ar) at –20 °C, protected from light, moisture, and strong oxidizing agents. The compound is stable under recommended storage conditions for extended periods. Desiccated storage is advised to prevent hydrolysis of the carboxamide bond.
Solubility & Preparation
Soluble in organic solvents including dimethyl sulfoxide (DMSO), dimethylformamide (DMF), and methanol; poorly soluble in aqueous buffers. For biological assays, prepare stock solutions in DMSO (10–50 mM) and dilute with assay buffer (final DMSO concentration ≤0.1–1% v/v) to achieve desired working concentrations. Note that precipitation may occur at high concentrations in aqueous media; sonication or gentle heating may assist dissolution.
Chemical Stability Considerations
The compound is sensitive to prolonged exposure to strong acids, bases, and nucleophilic conditions, which may hydrolyze the carboxamide bond or degrade the benzothiazole ring. Neutral to slightly acidic conditions (pH 5–7) are recommended for long-term stability in solution. Avoid repeated freeze-thaw cycles; aliquot stock solutions for single use to maintain integrity.
Intended Use
This product is intended for research, development, and laboratory use only. It is not for human therapeutic use, clinical diagnostics, veterinary treatment, or food applications unless explicitly authorized for regulated clinical trials. Standard laboratory safety practices (chemical fume hood, impermeable gloves, safety goggles) should be followed during handling. Avoid inhalation of dust and contact with skin or eyes.
Summary
The value of (1S,2S)-2-Fluoro-N-[6-(4-methyl-3-pyridinyl)-2-benzothiazolyl]cyclopropanecarboxamide (CAS: 2304918-81-6) lies in its unique combination of stereochemically defined fluorinated cyclopropane, rigid benzothiazole-pyridine biaryl scaffold, and potent, selective kinase inhibitory activity, which together enable its application across multiple research disciplines. Its use spans from targeted cancer therapy and immuno-oncology (as a lead kinase inhibitor) to chemical biology (as a selective probe for pathway mapping) and neuroscience (as a neuroprotective and anti-inflammatory agent). The well-defined stereochemistry, reliable synthetic accessibility, favorable ADME properties, and proven utility in both biochemical assays and preclinical disease models make this compound a dependable standard for drug discovery, chemical biology, and molecular pharmacology worldwide.
For more information, please contact: selina@coreychem.com
