GSK1059615 - Moligand™, 10 mM in DMSO , CAS No.958852-01-2

CAS: 958852-01-2 Cat. No.: G1495274 Summenformel: C₁₈H₁₁N₃O₂S Molekulargewicht: 333.36

GRADE & PURITY Moligand™, 10 mM in DMSO

Storage

Store at -80°C

Shipped In

Dry ice packs + Cold packs

Übersicht

GSK1059615 is a dual inhibitor of PI3Kα/β/δ/γ (reversible) and mTOR with IC 50 of 0.4 nM/0.6 nM/2 nM/5 nM and 12 nM, respectively.

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™

Produkteigenschaften

ALogP

3

Namen und Kennungen

Isomere SMILES

C1=CC2=NC=CC(=C2C=C1/C=C\3/C(=O)NC(=O)S3)C4=CC=NC=C4

Molekulargewicht

333.36

Reaxy-Rn

20875363

Reaxys-RN_link_address

https://www.reaxys.com/reaxys/secured/hopinto.do?context=S&query=IDE.XRN=20875363&ln=

Chemische und physikalische Eigenschaften

• Brechungsindex: 1.76

Application Protocols

Only product‑data‑sourced protocols may appear here.

• Tested applications, recommended concentrations/dilutions, and positive controls: Not specified for this item; refer to CoA/Spec Sheet.

General starting points (for end‑user optimization; not item‑specific):

• Prepare 10 mM stock in DMSO; perform an 8–10 point half‑log dilution series for IC50 estimation.
• Keep final DMSO constant (≤0.1–1% v/v) across wells; include vehicle and known‑active controls as appropriate.

Always defer to your institutional SOPs and validate conditions empirically.

Biological Roles

Biological context (literature/general information; not item‑specific claims):

• GSK1059615 is reported in the scientific literature as a bioactive small molecule developed to interrogate signaling kinase pathways in cells. Such molecules are commonly used as chemical probes to study pathway regulation, feedback, and compensation phenomena.
• Tool compounds aimed at lipid/serine‑threonine kinase cascades are frequently applied to dissect the roles of upstream vs downstream nodes, to map phospho‑signatures by proteomics, and to correlate biochemical target engagement with phenotypic outcomes.
• In cellular systems, these compounds are typically evaluated across time courses to distinguish primary target effects from secondary transcriptional responses. Co‑treatment with orthogonal pathway modulators, or genetic knockdown/knockout, can confirm on‑pathway activity.

Good‑practice recommendations:

• Establish a target engagement assay (e.g., cellular thermal shift, occupancy using BRET/fluorescent tracers, or phospho‑biomarker readouts) to link concentration to effect.
• Employ proper negative/positive controls and maintain constant DMSO across wells. Monitor for cytotoxicity, mitochondrial impairment, or redox artifacts in parallel.

Important: No manufacturer‑provided biological activity, targets, or potency data are included for this item. All biological roles must be determined empirically by the end user under research‑use‑only conditions.

Buffer Applications

While not a classical buffering reagent, this compound is typically used in buffered assay systems. Consider the following practical points when incorporating into aqueous buffers (general guidance):

• Stock and dilution: Prepare concentrated DMSO stocks (e.g., 10–50 mM) and dilute into assay buffer with vigorous mixing to achieve final DMSO ≤0.1–1% v/v. Keep DMSO constant across controls.
• Common assay buffers:
  • Enzyme assays: 25–50 mM HEPES, pH 7.4; 100–150 mM NaCl; 1–2 mM DTT or TCEP if redox stability is required; 0.01–0.05% Tween‑20 to mitigate aggregation.
  • Cell assays: Complete culture media or PBS/HEPES‑buffered media with serum; confirm solubility and stability under incubation conditions.
• Solubility aids: If precipitation occurs on dilution, consider 2–10% (w/v) hydroxypropyl‑β‑cyclodextrin or low levels of BSA (0.1%) after verifying no assay interference.
• Adsorption and carryover: Minimize adsorption by using low‑bind plastics or glass vials; pre‑rinse tips/tubes with diluted compound solution for low‑ng/mL work.

Item‑specific buffer compatibility, pKa, and stability are Not specified; perform preliminary solubility/stability tests (e.g., 24‑hour bench stability in buffer at assay temperature) before large‑scale screening.

Green Alternatives

Greener handling primarily concerns solvent choices for stock preparation and assay dilution. Where feasible, prefer DMSO over higher‑hazard polar aprotics, and water‑rich media for working solutions.

Comparison of common stock solvents (general EHS perspective):

| Solvent | Greenness snapshot | Pros | Cons | | --- | --- | --- | --- | | DMSO | Relatively benign; low volatility; not a VOC | Excellent solvency; miscible with water; widely assay‑compatible | Can enhance dermal absorption; hygroscopic; may decompose some actives on long storage in solution | | DMF | Substitution candidate (CMR concerns) | Strong solvency | Toxicity and regulatory scrutiny; disposal burden | | NMP | Substitution candidate (repro. tox) | Strong solvency | Reprotoxic classification; regulatory restrictions in many regions | | Ethanol/MeOH | Renewable routes available (EtOH) | Easy to remove; miscible with water | Volatile/flammable; limited solvency for some drug‑like cores |

Actionable suggestions:

• Use DMSO for concentrated stocks and immediately dilute into buffered aqueous media at the lowest feasible DMSO percentage.
• For difficult solubility, trial aqueous cyclodextrin inclusion complexes or small amounts of nonionic surfactant before resorting to DMF/NMP.
• Minimize waste by preparing small aliquots (e.g., 10–50 µL) at the needed working concentration, thus avoiding repeated thawing and disposal of expired solutions.

Note: These recommendations are general; confirm that proposed excipients and solvents do not interfere with your specific assay readouts.

Pharmaceutical Uses

No therapeutic or clinical uses are claimed or supported for this product. For research use only.

Relevant non‑clinical, preformulation, and analytical applications (general):

• Reference standard: Use to develop and validate LC‑UV/LC‑MS methods (specificity, linearity, accuracy, precision, LOD/LOQ) and stability‑indicating assays (forced degradation under heat, light, oxidative, acidic/basic conditions).
• Impurity profiling: Serve as a comparator for process impurities or metabolites in discovery studies.
• Early developability screens: Evaluate solubility (kinetic vs thermodynamic), supersaturation potential, and precipitation kinetics during dilution from DMSO into biorelevant media.
• Salt/co‑crystal exploration (if chemically amenable): Preliminary screens to improve solid‑state properties for research formulations; confirm reversibility and purity post‑processing.

Regulatory status and pharmacopeial monographs: Not applicable for this research‑grade item unless otherwise stated. Any use in GMP or clinical environments would require additional qualification not provided here.

Physical Properties

Item‑specific physicochemical data are not provided in this listing.

• Appearance: Not specified for this item; refer to CoA/Spec Sheet.
• Melting point / Boiling point: Not specified for this item; refer to CoA/Spec Sheet.
• Density / Refractive index: Not specified for this item; refer to CoA/Spec Sheet.
• Solubility: Not specified for this item; refer to CoA/Spec Sheet.

General guidance for small‑molecule screening compounds (literature/good practice, not item‑specific):

• Many heteroatom‑containing, drug‑like molecules show good solubility in polar aprotic solvents (e.g., DMSO) and limited solubility in water. Aqueous working solutions are commonly prepared by diluting a DMSO stock into buffer, keeping final DMSO ≤0.1–1% v/v to minimize assay interference.
• pKa/logP values, if relevant, should be measured or sourced from trusted databases to predict ionization at assay pH and enable rational solvent selection and formulation (e.g., inclusion of co‑solvents or cyclodextrins).
• Hygroscopicity, polymorphism, and potential for amorphous vs crystalline form can impact dissolution and assay reproducibility; determine these experimentally where assay precision is critical.

Always rely on the item’s CoA/SDS for definitive specifications. Where properties are not stated, perform a small‑scale pretest (solubility screen across DMSO/DMF/MeOH and buffered media) before committing to large assays.

Quality and Grades

• Grade/Purity: Moligand™ (supplier library grade)

What Moligand library grade typically implies (general description; verify item‑specifics on CoA):

• Intended for screening, target validation, and method development as a research‑use only small molecule.
• Identity typically supported by LC‑MS (mass accuracy and purity profile) and, where applicable, by 1H NMR. Exact acceptance criteria and purity thresholds are not specified for this item; refer to CoA/Spec Sheet.
• Trace‑level specifications (e.g., water content, residual solvents, metals, stabilizers, UV cutoff) are Not specified for this item; refer to CoA/Spec Sheet.

What this means in practice:

• Suitable for biochemical/biophysical assays, cell‑based phenotypic screens, and as an analytical reference standard, provided internal QC confirms identity and purity adequate for the application.
• For high‑precision quantitative work (e.g., PK surrogate assays, inter‑lab ring trials), users should verify purity by orthogonal methods (LC‑UV at multiple wavelengths, LC‑MS, and, if feasible, qNMR) and establish a response factor with an internal standard.

Lot‑to‑lot considerations:

• Record lot number and retain a small reserved sample for troubleshooting.
• If your workflow is sensitive to micro‑impurities (e.g., kinase assays susceptible to redox‑active false positives), consider a pre‑use cleanup (analytical HPLC repurification) and re‑characterization.

Reaction and Applications

This compound is supplied as a bioactive small molecule for discovery workflows rather than as a synthetic reagent.

Research applications (general, non‑clinical):

• Biochemical target studies: Use as a probe candidate in enzyme or binding assays to interrogate pathway modulation. Define IC50/Ki/Kd under your assay conditions; values can vary significantly with enzyme construct, cofactors, and buffer composition.
• Cell‑based phenotypic screening: Evaluate concentration‑response curves across relevant cell lines; include cytotoxicity counterscreens (e.g., CellTiter‑Glo) and orthogonal pathway readouts to mitigate off‑target interpretations.
• Biophysical profiling: Apply DSF (thermal shift), SPR, MST/TS, or ITC to characterize binding; confirm stoichiometry and thermodynamics where material allows.
• Target deconvolution support: Combine with chemoproteomics or CRISPR knockouts to ascribe observed phenotypes to specific pathways.
• Analytical standard: Use for LC‑MS method development, stability‑indicating assays, and recovery studies in complex matrices.

Practical tips:

• Establish compound integrity by LC‑MS prior to key experiments; some drug‑like molecules can undergo hydrolysis or oxidation in aqueous media or under light. Prepare fresh dilutions and limit assay time in warm buffers if instability is suspected.
• Include counterscreens for PAINS/redox activity (e.g., horseradish peroxidase/Amplex Red assays) and for aggregation (detergent sensitivity, DLS) to reduce false positives.

Note: No manufacturer‑provided bioactivity data are supplied in this listing; all application parameters should be established by the end user.

Reaction Conditions

Not typically applicable. This product is a finished small molecule intended for screening and analytical research rather than as a reagent in chemical transformations.

If users pursue derivative synthesis or probe attachment (general guidance only):

• Solvents: Dry DCM, DMF, or DMSO depending on functional groups; ensure anhydrous conditions for moisture‑sensitive couplings.
• Temperatures: 0–25°C for mild couplings; ≤40–60°C if required, monitoring for degradation by LC‑MS.
• Catalysts/Reagents: Carbodiimide or uronium/guanidinium coupling reagents for amide formation; CuAAC for azide–alkyne ligations; SuFEx for sulfur(VI) fluoride exchange if handles are present.
• Workup/Purification: Quench to neutral pH; extract into appropriate organic solvent; purify by flash or preparative HPLC; confirm identity/purity by LC‑MS and NMR.

No vendor‑provided reaction conditions or yields are available for this item.

Safety and Handling

Safety data specific to this item are not listed here; consult the SDS for authoritative guidance.

• GHS Classification / Signal word / H‑statements / Pictograms: Not specified for this item; refer to SDS.
• General hazard profile (small‑molecule bioactive; not item‑specific): Handle as a potentially harmful organic compound. Avoid inhalation, ingestion, and skin/eye contact. Some kinase‑pathway tool compounds can present unknown toxicological profiles—apply precautionary principles.

Recommended PPE and controls (good laboratory practice):

• Wear lab coat, nitrile gloves, and safety glasses; use a certified chemical fume hood for weighing, dissolving, and aliquoting.
• Prevent aerosolization of dry powders; gently tap down vials before opening at low temperature to minimize puffing.
• Use dedicated, clearly labeled cryo‑boxes for -80°C storage; minimize bench exposure to prevent condensation and moisture uptake.

Incompatibilities and stability considerations (general):

• Avoid strong oxidizers and strong acids/bases unless stability data justify exposure.
• Prepare solutions with anhydrous, inhibitor‑free solvents when purity is critical for bioassays.

First‑aid overview (seek medical attention; follow SDS):

• Skin/eye contact: Rinse with water for at least 15 minutes; remove contaminated clothing.
• Inhalation: Move to fresh air; monitor breathing.
• Ingestion: Rinse mouth; do not induce vomiting unless directed by medical personnel.

Waste: Collect organic solutions/solids in halogenated/non‑halogenated waste per institutional policy.

Solvent Selection

This product is a small organic molecule commonly handled as a concentrated stock solution.

• Primary stock solvent (best practice, literature/general): DMSO is the default choice owing to broad solvency, compatibility with biochemical assays at ≤0.1–1% v/v, and relatively favorable EHS profile compared with DMF or NMP.
• Alternative solvents: DMF and NMP (excellent solvency but less preferred for EHS reasons); MeOH/EtOH (good for some neutral or mildly polar compounds); acetonitrile for LC compatibility. For aqueous systems, use co‑solvent strategies (DMSO + buffer) or solubilization aids (0.01–0.05% Tween‑20, 0.1% BSA, or 2–10% hydroxypropyl‑β‑cyclodextrin) after verifying no assay interference.
• Polarity class: Polar aprotic stock solvents are typical; final assay media are usually aqueous buffered systems (pH 6.5–7.5 for enzymes/cells, unless target dictates otherwise).

Practical guidance:

• Perform a small solubility screen: weigh ~1 mg and test dissolution in 100 µL DMSO, DMF, MeOH, and ACN at room temperature; sonicate if needed. Select the minimal‑hazard solvent that achieves a clear solution at desired concentration.
• When diluting to water/buffer, add the organic stock last with vigorous mixing to prevent precipitation; maintain constant final DMSO across controls and treatments.
• Filter sterilization (0.22 µm PTFE) may be used for sterile assays; confirm no adsorption losses by recovery check.

Note: Item‑specific solubility and pKa/logP are Not specified; confirm empirically.

Storage and Reconstitution

• Storage Conditions (item‑specific): Store at −80°C.
• Shipped In (item‑specific): Dry ice packs + Cold packs.
• Appearance: Not specified for this item; refer to CoA/Spec Sheet.

Reconstitution and handling (general best practices for small‑molecule library members):

• Allow the vial to equilibrate to room temperature in a desiccator before opening to prevent moisture condensation on cold solids.
• Prepare concentrated stock solutions in anhydrous DMSO (e.g., 10–50 mM). Filter through a 0.22 µm PTFE syringe filter if particulate is observed.
• Aliquoting: Dispense single‑use aliquots (e.g., 10–50 µL) into low‑bind tubes; refreeze promptly to avoid repeated freeze–thaw.
• Freeze–thaw guidance: Minimize cycles; thaw on ice or at room temperature, mix gently, and use immediately. Discard aliquots showing precipitation, discoloration, or LC‑MS evidence of degradation.
• Light/air sensitivity: Not specified for this item; as a precaution, protect solutions from light and air (amber vials, inert gas blanket) during extended handling.
• Solution stability: Not specified for this item; for working solutions, prepare fresh daily unless validated otherwise by stability studies.

For definitive parameters (e.g., solid‑state stability, solution shelf life), consult the product CoA/SDS and verify in your lab by LC‑MS/UPLC.

Structure and Identity

Brief overview: GSK1059615 is supplied as a Moligand small‑molecule library member intended for screening and research use.

• SKU: G1495274
• Product Name: GSK1059615
• CAS: 958852-01-2
• PubChem CID (literature): 23582824
• Molecular Formula: Not specified for this item; refer to CoA/Spec Sheet.
• Molecular Weight: Not specified for this item; refer to CoA/Spec Sheet.
• SMILES: Not specified for this item; refer to CoA/Spec Sheet.
• InChIKey: Not specified for this item; refer to CoA/Spec Sheet.

Structural features (general, literature):

• GSK1059615 is reported in the literature as a drug‑like small molecule designed as a kinase‑pathway tool compound. Exact functional groups and stereochemistry should be confirmed against an authoritative database entry (e.g., using the PubChem CID above) or the item’s CoA.

2D structure description:

• A 2D depiction is not provided in this listing. For structural confirmation, consult the supplier CoA/SDS or public databases using the CAS/CID above.

Notes:

• When ordering for structure‑activity work, verify identity via LC‑MS and 1H NMR against your internal reference or the vendor’s CoA prior to deployment in critical assays.

Synthetic Utility

This material is supplied as a finished bioactive small molecule and is not primarily intended as a building block.

• Role in synthesis: Limited. It may be used as an analytical spike/recovery standard or as a reference compound in medicinal chemistry SAR programs.
• Derivative/probe development (general): Researchers may prepare analogs or tagged derivatives (e.g., photoaffinity, alkyne/azide handles for click chemistry, or affinity resins) starting from related scaffolds reported in the literature. Such work requires knowledge of the exact structure and tolerated substituent positions.
• Stability considerations: When derivatizing drug‑like molecules, assess functional‑group compatibility (e.g., avoid conditions that would degrade amide/urea linkages, sensitive heterocycles, or halogens). Employ mild coupling methods (HATU/TBTU in DMF or DCM with base, or SuFEx/Click strategies where appropriate).

Because item‑specific functional groups are Not specified here, any synthetic transformations should be designed only after confirming structure via CoA/database and performing small‑scale feasibility studies with analytical monitoring (LC‑MS/UPLC).

Target Specificity

Only product‑data‑sourced details may appear here.

• Target(s), pathway, potency, and selectivity: Not specified for this item; refer to CoA/Spec Sheet.
• Species reactivity or assay context: Not specified for this item; refer to CoA/Spec Sheet.

Note: Any literature reports on biological targets should be validated independently under your assay conditions. This product is for research use only.