CDK7/12-IN-1 - Moligand™, 10 mM in DMSO , CAS No.2654075-94-0

CAS: 2654075-94-0 Cat. No.: C1499117 Summenformel: C₂₅H₃₄N₈O Molekulargewicht: 462.59

GRADE & PURITY Moligand™, 10 mM in DMSO

Storage

Store at -80°C

Shipped In

Dry ice packs + Cold packs

Übersicht

CDK7/12-IN-1 is a selective CDK7/12 inhibitor with IC 50 s of 3 and 277 nM for CDK7 and CDK 12, respectively. CDK7 and CDK12 inhibition is an effective strategy to inhibit tumour growth.

Specifications

Spezifikationen & Reinheit

Moligand™, 10 mM in DMSO

Storage

Store at -80°C

Verschickt in

Dry ice packs + Cold packs

Dieses Produkt erfordert Kühlkettenversand. Grundversand und andere Economy-Optionen sind nicht verfügbar.

Note

Moligand™

Aktionsart

INHIBITOR

Namen und Kennungen

Molekulargewicht

462.59

Application Protocols

No tested application protocols or validated dilutions are provided in the Product Data for this item.

• General guidance for use in assays (not item-specific; verify experimentally):
  • Biochemical kinase assays: Titrate across a broad range (e.g., 0.1 nM to 30 µM) to capture full dose–response. Keep ATP concentration near Km to best reveal competitive inhibition.
  • Cell-based studies: Begin with low-nanomolar to low-micromolar ranges; verify on-target engagement via phospho-CTD immunoblotting or transcriptional readouts. Maintain consistent vehicle (DMSO) controls.
  • Stock handling: Prepare DMSO stocks, aliquot to single-use vials, and avoid repeated freeze–thaw.

These are general suggestions only. For definitive, product-specific protocols, refer to the CoA/Spec Sheet or develop SOPs based on pilot experiments.

Biological Roles

CDK7/12-IN-1 is designated to modulate cyclin-dependent kinase 7 (CDK7) and cyclin-dependent kinase 12 (CDK12) based on its name. Item-specific potency and selectivity are not provided in the Product Data; the following summarizes biological context from general literature.

• CDK7 (general biology):

  • Functions as part of the TFIIH complex, phosphorylating the RNA polymerase II C-terminal domain (Pol II CTD) at Ser5/Ser7 during transcription initiation and promoter clearance.
  • Acts as a CDK-activating kinase (CAK) for multiple CDKs via T-loop phosphorylation, influencing cell-cycle and transcriptional control.

• CDK12 (general biology):

  • Regulates transcription elongation of genes involved in DNA damage response and RNA processing by promoting Pol II CTD Ser2 phosphorylation.
  • CDK12 integrity influences expression of long, exon-rich genes, including those in homologous recombination pathways.

• Research utility of dual CDK7/12 inhibitors (general):

  • Enable interrogation of transcriptional regulation at initiation and elongation phases.
  • Facilitate mapping of gene expression programs dependent on CTD phosphorylation states and assessment of genome stability pathways.
  • Support chemical-genetic studies such as rescue with kinase-dead mutants or orthogonal readouts (e.g., phospho-CTD immunoblotting, nascent RNA labeling).

• Assay readouts (general):

  • Biochemical kinase assays (radiometric, ADP-Glo, TR-FRET), cellular phospho-CTD profiling, global run-on sequencing (GRO-seq), and transcriptomics.

All uses are for research only; no medical or clinical claims are made.

Buffer Applications

This product is not a buffering agent and is not used to set or maintain solution pH.

• Practical note:

  • When preparing assay solutions, dissolve in an appropriate solvent (commonly DMSO) and dilute into your chosen buffer (e.g., HEPES- or Tris-based assay buffers for kinase studies). Maintain a consistent final solvent percentage across samples.

• Buffer recipes and pKa ranges are not applicable to this compound. For buffer system guidance, refer to HEPES, Tris, or phosphate buffer products.

Green Alternatives

As a small-molecule inhibitor used primarily in biochemical or cellular assays, the main environmental considerations relate to solvent choice and waste minimization rather than substitution of the active compound.

• Solvent choices (general guidance):

  • Prefer DMSO for stock solutions due to low volatility and established biocompatibility at low percentages; minimize final DMSO to the lowest effective level (often ≤0.1–0.2% v/v) to reduce solvent burden.
  • Where possible, replace DMF/NMP with DMSO or aqueous-compatible cosolvents to improve environmental and operator safety profiles.

• Waste reduction strategies:

  • Prepare small aliquots at concentrations aligned with experimental throughput to avoid repeated freeze–thaw and disposal of expired material.
  • Use micro-scale assay formats (e.g., 384- or 1536-well) to reduce compound and solvent use without compromising data quality.
  • Implement sealed-plate handling to minimize evaporative losses and volatile solvent emissions.

• Comparison of common solvents (general; literature-based):

  • DMSO: Low vapor pressure, good solvency, favorable EHS relative to DMF/NMP; potential skin penetration risk—use gloves.
  • Ethanol: Renewable feedstocks possible, but limited solubility for many kinase inhibitors and higher volatility.
  • DMF/NMP: Strong solvency but reproductive toxicity concerns; avoid in biological testing where feasible.

No greener “substitute compound” is suggested because bioactivity is target-specific; instead, focus on greener handling practices and solvent selection.

Pharmaceutical Uses

CDK7/12-IN-1 is provided strictly for research use only (per Product Data). No therapeutic, diagnostic, or clinical uses are endorsed or implied.

• Research and development context (general):

  • Serves as a chemical tool in drug discovery workflows to interrogate transcriptional CDKs, informing target validation, medicinal chemistry direction, and biomarker strategy.
  • Can function as a reference control in high-content screens or orthogonal assays profiling transcriptional outputs.

• Formulation/excipient perspective:

  • Not used as a pharmaceutical excipient. Any formulation-like preparation (e.g., DMSO stocks, aqueous dilutions, or vehicles for in vivo model development) should be considered exploratory research only and validated for stability, compatibility, and dose accuracy.

• Regulatory status:

  • No pharmacopeial monograph or compendial status is provided for this item. Any claims about GMP status, residual solvent classes, or impurity thresholds are not specified; refer to CoA/Spec Sheet if required.

All handling should adhere to institutional policies for investigational research chemicals.

Physical Properties

• Item-specific physico-chemical specifications:

  • Appearance: Not specified for this item; refer to CoA/Spec Sheet.
  • Molecular Weight: Not specified for this item; refer to CoA/Spec Sheet.
  • Melting point, boiling point, density, refractive index, logP/logD, pKa, UV cutoff: Not specified for this item; refer to CoA/Spec Sheet.
  • Aqueous or organic solubility limits: Not specified for this item; refer to CoA/Spec Sheet.

• General guidance for kinase inhibitors (literature/typical, not item-specific):

  • Physical state: Typically solid powders with moderate crystallinity.
  • Solubility: Frequently soluble in polar aprotic solvents (e.g., DMSO) at 10–50 mM; variable aqueous solubility that can be improved by cosolvents (DMSO, ethanol) or pH adjustment if ionizable groups are present.
  • Stability: Many heteroaromatic inhibitors are stable under dry, dark, low-temperature conditions; sensitivity to moisture, oxidation, or strong light is variable and should be confirmed per CoA/SDS.

• Practical notes (general):

  • Prepare concentrated DMSO stock (e.g., 10 mM) and dilute into assay buffers immediately before use to minimize precipitation.
  • If aqueous precipitation occurs, consider gentle heating (<40°C), sonication, or incremental cosolvent (≤1% v/v DMSO final), ensuring assay compatibility.
  • Filter sterilization (0.22 µm PTFE) may be applied to working solutions when compatible with solvent composition.

Always defer to the item-specific CoA and SDS for authoritative physical property data.

Quality and Grades

• Item-specific grade (from Product Data):

  • Grade/Purity: Moligand™

• What Moligand™ typically signifies (general description; not a specification):

  • Moligand™ designates small-molecule ligands intended for research screening, target validation, and chemical biology. Such materials are commonly provided with identity confirmation (e.g., NMR/LC-MS) and screening-appropriate purity suitable for in vitro assays. Exact acceptance criteria (purity %, residual solvents, water, counter-ions, salt form) are product-specific.

• For this item specifically:

  • Purity level, analytical methods, residual solvent limits, water content, metal limits, and UV profile: Not specified for this item; refer to CoA/Spec Sheet.
  • Salt form, polymorph, and counter-ion (if any): Not specified for this item; refer to CoA/Spec Sheet.

• Practical implications for users:

  • Screening-grade compounds are typically fit for biochemical/biophysical assays, cellular studies, and SAR exploration. If you require quantitative pharmacology or in vivo enabling studies, verify lot-specific purity, salt form, and stability from the CoA and request additional QC as needed.
  • If performing analytical HPLC/UPLC quantitation or mass-balance studies, confirm extinction coefficients and detector response for your conditions, and consider orthogonal purity assessment (qNMR) when critical.

• Documentation:

  • For reproducibility, archive the lot-specific CoA, analytical chromatograms, and any user-performed verification (e.g., LC-MS retention time, purity in your mobile phase).

Reaction and Applications

This product is a small-molecule research inhibitor intended for chemical biology and assay-based applications rather than as a synthetic reagent.

• Intended research applications (general; no therapeutic claims):

  • Biochemical kinase inhibition assays targeting CDK7 and CDK12 to probe transcriptional CDK function.
  • Cell-based target engagement studies (e.g., measuring RNA Pol II CTD phosphorylation states) to assess on-target effects.
  • Time-course studies of transcriptional responses and DDR (DNA damage response) signaling dependent on CDK12 activity.
  • Use as a reference/positive control compound in screening cascades exploring CDK7/12 pathways.

• Not typically applicable:

  • Named organic reactions or use as a coupling/activation reagent are not relevant to this compound class. For synthetic chemistry needs, refer to building-block reagents.

• Practical assay considerations (general):

  • Maintain a consistent DMSO concentration across wells/replicates.
  • Include counter-screens against kinases with overlapping ATP sites to assess selectivity if the dataset is not provided.
  • Confirm reversibility/irreversibility and time dependence of inhibition experimentally (preincubation studies) since CDK inhibitors can vary in binding kinetics.
  • Verify compound stability in assay media over the duration of the experiment (LC-MS check of remaining parent).

Item-specific potency, selectivity profile, and mechanistic binding mode are not provided in the Product Data; consult literature sources or request additional documentation if needed.

Reaction Conditions

This product is not intended for use as a reagent in chemical synthesis; thus, conventional reaction conditions (solvent, temperature, catalysts) are not typically applicable.

• Assay preparation conditions (general guidance for small-molecule inhibitors; not item-specific):

  • Stock solutions: Prepare in anhydrous DMSO (commonly 10–50 mM). Mix thoroughly and verify clarity.
  • Working solutions: Dilute into assay buffer immediately before use. Maintain consistent final DMSO across all wells/samples (often ≤0.1–0.5% v/v, depending on assay tolerance).
  • Temperature: Conduct biochemical assays at recommended enzyme temperatures (often 25–30°C) and cellular assays at physiological conditions (37°C, 5% CO2) as applicable.
  • Controls: Include vehicle controls, positive/negative controls, and, if possible, time-dependent preincubation to assess binding kinetics.

• Stability checks (general):

  • Confirm short-term stability of the compound in assay matrix by LC-MS (parent peak area over time) and monitor for precipitation or adsorption.

No yields, catalytic systems, or synthetic reaction timelines are relevant for this item.

Safety and Handling

• Item-specific hazard data (from Product Data):

  • 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.

• Storage and shipping (from Product Data):

  • Storage Conditions: Store at −80°C.
  • Shipped In: Dry ice packs + Cold packs.

• General laboratory precautions (advisory; defer to SDS):

  • Handle in a chemical fume hood; avoid inhalation of dust or aerosols and contact with skin/eyes.
  • Recommended PPE: lab coat, safety glasses, and appropriate chemical-resistant gloves (e.g., nitrile). Use double-gloving for extended handling of DMSO solutions.
  • Incompatibilities (general): strong oxidizers, strong acids/bases (for solutions), and reactive acylating/alkylating agents. Avoid prolonged exposure to light and moisture unless stability is confirmed.

• First-aid overview (general):

  • Skin/eye contact: Rinse with copious water for ≥15 minutes; remove contaminated clothing. Seek medical attention.
  • Inhalation: Move to fresh air; monitor breathing; seek medical attention if symptoms persist.
  • Ingestion: Rinse mouth; do not induce vomiting; seek medical attention.

• Spill and disposal (general):

  • Contain with inert absorbent, prevent dust generation, and collect in labeled waste for disposal per institutional and local regulations.

Consult the product SDS for definitive hazard classification and response measures.

Solvent Selection

CDK7/12-IN-1 is a small-molecule inhibitor where the primary consideration is preparing reliable stock solutions for biochemical or cell-based assays.

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

• General solvent guidance for kinase inhibitors (literature/typical, not item-specific):

  • Primary solvent: DMSO due to broad solubilizing power and biocompatibility at ≤0.1–0.5% v/v in many assays.
  • Secondary solvents/co-solvents: DMF or NMP for initial dissolution (laboratory use only; typically diluted into DMSO or buffer), ethanol or PEG400 for specialized applications.
  • Aqueous work: Dilute DMSO stocks into assay buffer with vigorous mixing; include surfactant (e.g., 0.01–0.05% Tween-20) when compatible to reduce aggregation/precipitation.

• Buffer compatibility (general):

  • Many kinase assays use HEPES- or Tris-based buffers with Mg2+/ATP. Maintain consistent final DMSO content across controls and treated samples.

• Practical tips:

  • Prepare concentrated DMSO stocks (e.g., 10–50 mM); verify clarity after dilution to working concentrations.
  • If precipitation occurs on dilution, add compound to buffer last, with high-speed mixing, or pre-equilibrate at 37°C.
  • Avoid glass adsorption for very lipophilic compounds by using low-binding plasticware.

• Comparison (general):

  • DMSO vs ethanol: DMSO typically affords higher solubility and lower volatility; ethanol can be preferable for certain biological contexts but has tighter concentration limits in cells.
  • DMSO vs DMF/NMP: DMF/NMP can solubilize refractory solids but are less favored in biological assays; use only as minor cosolvents if required.

Storage and Reconstitution

• Item-specific storage and shipping (from Product Data):

  • Storage Conditions: Store at −80°C.
  • Shipped In: Dry ice packs + Cold packs.

• Reconstitution (item-specific details not provided):

  • Solvent, concentration limits, and stability after reconstitution: Not specified for this item; refer to CoA/Spec Sheet.

• General best practices for small-molecule inhibitors (not item-specific):

  • Reconstitution: Prepare concentrated stock solutions in anhydrous DMSO (e.g., 10–50 mM) under inert atmosphere if feasible. Vortex and, if needed, briefly sonicate to ensure complete dissolution.
  • Aliquoting: Dispense into single-use, low-binding, light-protective vials to minimize adsorption and freeze–thaw cycles.
  • Storage of solutions: Store frozen stocks at −80°C. Avoid repeated freeze–thaw; thaw on ice and use immediately. Discard any turbid or precipitated solutions.
  • Light/moisture: Protect from light and moisture during handling. Allow vials to equilibrate to room temperature in a desiccated environment before opening to reduce condensation.

• Stability checks:

  • Verify integrity periodically by LC-MS or HPLC-PDA after storage. Establish an internal retest date if the CoA does not specify one.

For any lot-specific stability, solubility, or reconstitution instructions, defer to the CoA/Spec Sheet.

Structure and Identity

Brief overview: CDK7/12-IN-1 is a small-molecule research inhibitor designated for cyclin-dependent kinases CDK7 and CDK12 based on its name. Detailed structural identifiers are not provided in the Product Data.

• Item-specific identifiers (from Product Data):

  • CAS: 2654075-94-0
  • InChIKey: Not specified for this item; refer to CoA/Spec Sheet.
  • 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.
  • Grade: Moligand™

• Structural features (general/literature context for CDK inhibitors; not item-specific):

  • Many CDK inhibitors are heteroaromatic, hydrogen-bonding-competent scaffolds designed to engage the ATP-binding site via donor/acceptor motifs and planar aromatic systems. Typical features include amide/urea linkers, heterocycles (e.g., quinazolinone, pyrimidinone, pyrazole), and substituents that reach the gatekeeper pocket.
  • CDK7/12-selective chemotypes in literature often present hinge-binding motifs (e.g., substituted pyrimidines) and solubilizing side chains to balance permeability and target residence time.

• 2D structure description (general, not item-specific):

  • Expect a polyheteroaromatic core with one or more ring systems, at least one H-bond acceptor/donor pair to anchor the kinase hinge, and peripheral substituents for kinase-family selectivity. Exact ring count, stereochemistry, and substituent pattern are not provided for this product and should be confirmed in the CoA/Spec Sheet.

Synthetic Utility

CDK7/12-IN-1 is a finished small-molecule inhibitor and is not generally employed as a reagent or building block in synthetic organic chemistry.

• Non-applicability to standard transformations:

  • It is not designed for use as a coupling partner, catalyst, or stoichiometric reagent in named reactions (e.g., Suzuki, amide coupling). Any synthetic modification would be part of medicinal chemistry SAR development rather than routine synthesis.

• If derivatization is contemplated (general medicinal chemistry considerations):

  • Prodrug or solubilizing group installation (e.g., tertiary amine salts, carbonate linkers) may be explored to tune properties, but such modifications create new entities requiring full recharacterization.
  • Bioorthogonal tagging (e.g., alkyne/azide handles) can enable chemical proteomics; ensure that tagging sites do not disrupt hinge-binding motifs essential for kinase inhibition.

• Data needs before derivatization:

  • Full structural information (SMILES, InChIKey), stereochemistry, and SAR context are prerequisites; these are not provided in the Product Data and must be obtained from the CoA/Spec Sheet or literature mapping to the CAS.

For practical synthetic chemistry needs, refer instead to dedicated building blocks and reagents.

Target Specificity

Target specificity data (e.g., IC50/Ki values, kinome selectivity panels, binding mode) are not provided in the Product Data for this item.

• Applicability note:

  • This section typically applies to biologics (antibodies, proteins) or small molecules with fully disclosed profiling. For this listing, no lot-specific or literature-based potency/selectivity values are supplied.

• Recommendation:

  • Consult the CoA/Spec Sheet for any available target panel data. If absent, users should perform in-house profiling (biochemical assays against CDK7, CDK12, and off-target kinases; cellular phospho-CTD readouts) to establish effective working ranges and selectivity under their conditions.