Rigosertib (ON-01910) - 10mM in DMSO , CAS No.1225497-78-8

CAS: 1225497-78-8 Cat. No.: R408527 Formula: C₂₁H₂₄NO₈S・Na Peso molecolare: 473.43

GRADE & PURITY 10mM in DMSO

Synonyms

N-​[2-​methoxy-​5-​[[[2-​(2,​4,​6-​trimethoxyphenyl)​ethenyl]​sulfonyl]​methyl]​phenyl]​-​glycine,sodium salt (1:1)

Storage

Store at -80°C

Shipped In

Dry ice packs + Cold packs

Panoramica

Information

Rigosertib (ON-01910) is a non-ATP-competitive inhibitor ofPLK1withIC50of 9 nM in a cell-free assay. It shows 30-fold greater selectivity against Plk2 and no activity to Plk3. Rigosertib inhibitsPI3K/Aktpathway and activates oxidative stress signals. Rigo
In vitro

Rigosertib is non-ATP-competitive inhibitor to PLK1 with IC50 of 9 nM. Rigosertib also exhibits inhibition against PLK2, PDGFR, Flt1, BCR-ABL, Fyn, Src, and CDK1, with IC50 of 18-260 nM. Rigosertib shows cell killing activity against 94 different tumor cell lines with IC50 of 50-250 nM, including BT27, MCF-7, DU145, PC3, U87, A549, H187, RF1, HCT15, SW480, and KB cells. While in normal cells, such as HFL, PrEC, HMEC, and HUVEC, Rigosertib has little or no effect unless its concentration is greater than 5-10 μM. In HeLa cells, Rigosertib (100-250 nM) induces spindle abnormalities and apoptosis. Rigosertib also inhibits several multidrug resistant tumor cell lines, including MES-SA, MES-SA/DX5a, CEM, and CEM/C2a, with IC50 of 50-100 nM. In DU145 cells, Rigosertib (0.25-5 μM) blocks cell cycle progression in G2/M phase, results in an accumulation of cells containing subG1 content of DNA, and activates apoptotic pathways. In A549 cells, Rigosertib (50 nM-0.5 μM) induces loss of viability and caspase 3/7 activation. In a recent study, Rigosertib induces apoptosis in chronic lymphocytic leukemia (CLL) cells without toxicity against T-cells or normal B-cells. Rigosertib also abrogates the pro-survival effect of follicular dendritic cells on CLL cells and reduces SDF-1-induced migration of leukemic cells.

In vivo

In mouse xenograft models of Bel-7402, MCF-7, and MIA-PaCa cells, Rigosertib (250 mg/kg) markedly inhibits tumor growth. Rigosertib (200 mg/kg) shows inhibition on tumor growth in a mouse xengraft model of BT20 cells.
Cell Data

cell lines：

Concentrations：1 nM - 10 μM, dissolved in DMSO as stock solution.

Incubation Time：96 hours

Powder Purity:≥98%

Specifications

Sinonimi

N-​[2-​methoxy-​5-​[[[2-​(2,​4,​6-​trimethoxyphenyl)​ethenyl]​sulfonyl]​methyl]​phenyl]​-​glycine,sodium salt (1:1)

Specifiche e purezza

10mM in DMSO

Meccanismi biochimici e fisiologici

Rigosertib (ON-01910) is a non-ATP-competitive inhibitor of PLK1 with IC50 of 9 nM in a cell-free assay. It shows 30-fold greater selectivity against Plk2 and no activity to Plk3. Rigosertib inhibits PI3K/Akt pathway and activates oxidative stress signals

Condizioni di conservazione di stoccaggio

Store at -80°C

Spedito in

Dry ice packs + Cold packs

Questo prodotto richiede spedizione a catena fredda. I servizi di terra e altri servizi economici non sono disponibili.

Nomi e identificatori

Isomeri SMILES

COC1=C(C=C(C=C1)CS(=O)(=O)/C=C/C2=C(C=C(C=C2OC)OC)OC)NCC(=O)[O-].[Na+]

Peso molecolare

473.43

Reaxy-Rn

26934487

Reaxys-RN_link_address

https://www.reaxys.com/reaxys/secured/hopinto.do?context=S&query=IDE.XRN=26934487&ln=

Proprietà chimiche e fisiche

• Solubilità: Solubility (25°C) In vitro DMSO: 48 mg/mL (198.91 mM)

Application Protocols

No vendor‑validated application protocols are provided for this SKU. The following general, literature‑style guidance is offered for typical small‑molecule cell‑based studies:

• Stock solution: Prepare 10–50 mM in anhydrous DMSO; aliquot (e.g., 10–50 µL) and store at −80°C. Avoid repeated freeze–thaw cycles.
• Cell treatment (general):
  • Plate cells to 60–80% confluence. Add compound to achieve final DMSO ≤0.1–0.5% v/v.
  • Perform a concentration–response (e.g., 8–10 points; 3‑fold serial dilutions). Include vehicle control and, if available, an orthogonal probe.
  • Incubation times commonly range 2–72 h depending on the readout; verify with pilot experiments.
• Readouts: Viability assays (e.g., CellTiter‑Glo), cell‑cycle analysis (flow cytometry), phospho‑signaling by Western blot or ELISA, and imaging‑based phenotypes (general suggestions).
• Data quality: Use at least triplicate wells per condition; repeat across passages. Confirm compound identity/purity by LC–MS if critical conclusions depend on its activity.
• Note: Adjust conditions based on your cell model and institutional SOPs. This guidance does not replace method validation.

Biological Roles

• Research use only (per Product Data). No clinical or diagnostic use is implied.
• Reported biological activities (literature, general):
  • Initially described as a mitotic kinase pathway modulator; numerous studies report effects on PLK1‑associated signaling and microtubule/mitotic progression phenotypes.
  • More recent literature proposes a RAS‑mimetic mechanism that perturbs RAS–effector interactions (e.g., RAF/PI3K binding interfaces), leading to altered downstream signaling. The exact dominant mechanism may be context‑dependent and is an active area of study.
• Applications in experimental systems (literature, general):
  • Cell‑based assays in hematologic and solid‑tumor lines to probe cell‑cycle checkpoint control and stress signaling.
  • Chemical‑genetic interaction screens and phospho‑signaling profiling to map pathway dependencies.
• Good practices for biological studies:
  • Use concentration–response curves and multiple time points to delineate primary versus secondary effects.
  • Include orthogonal probes and, where possible, genetic perturbations (e.g., siRNA/CRISPR) to support target assignment.
  • Confirm on‑target activity with pathway‑specific biomarkers and rescue experiments.

Buffer Applications

This item is not a buffering agent and is not typically used to prepare or maintain pH in biochemical systems. For experimental work, rigosertib is usually dosed from an organic stock solution (commonly DMSO) into pre‑selected biological buffers (e.g., PBS, HBSS, culture media). Select the buffer based on the biological assay; maintain consistent co‑solvent levels across controls and treatments.

Green Alternatives

Because this item is a specific bioactive small molecule (not a process solvent or bulk reagent), green‑chemistry substitution is not typically applicable. However, greener handling practices can be considered for solutions and workflows:

• Solvent and footprint considerations (general):
  • Use minimal DMSO volumes and high‑concentration master stocks to reduce solvent use.
  • For washing and cleanup, prefer ethanol/water over chlorinated solvents where feasible.
  • Employ microplate‑based assays or miniaturized reaction volumes to reduce waste.
• Storage and logistics:
  • Shipments are already designed to minimize degradation (dry ice + cold packs as specified). Consolidated shipments reduce packaging waste.
• Alternative probes (literature, general): If pathway modulation is the goal, consider orthogonal chemical probes with distinct structures/mechanisms to reduce reliance on any single compound and to strengthen mechanistic conclusions. Selection should be guided by published selectivity and off‑target profiles.

Pharmaceutical Uses

• Scope of use: For research use only (per Product Data). No therapeutic, diagnostic, or clinical claims are made.
• Laboratory and preformulation contexts (general):
  • Employed as a reference research material in analytical method development (e.g., LC–MS/MS quantitation in matrices) and in vitro ADME profiling (solubility, stability, protein binding) for academic/industrial research.
  • Useful for evaluating formulation strategies at small scale (e.g., DMSO/PEG cosolvent systems, cyclodextrin inclusion, or lipid‑based vehicles) to explore solubility and stability in research settings.
• Regulatory status: Not specified for this item; not supplied with pharmacopeial certification.
• Impurity and stability studies: Researchers may use this compound as a control to assess degradation pathways (oxidation, hydrolysis, photolysis) and to validate stability‑indicating analytical methods (general). Always confirm acceptance criteria and reference standards internally.

Physical Properties

• Appearance: Not specified for this item; refer to CoA/Spec Sheet.
• Melting point: Not specified for this item; refer to CoA/Spec Sheet.
• Boiling point: Not applicable/rarely reported for this class; decomposes before boiling (general, literature comment for complex bioactives).
• Density: Not specified for this item; refer to CoA/Spec Sheet.
• Solubility (practical guidance): Typically prepared as concentrated DMSO stocks for biological assays; aqueous solubility can depend strongly on counter‑ion/salt form and pH (literature, general). For this specific catalog item, verify recommended solvents on the CoA.
• LogP/logD, pKa, refractive index: Not specified for this item; refer to CoA/Spec Sheet.
• UV–Vis characteristics: Often shows strong UV absorbance due to conjugated aromatic/alkenyl motifs (literature, general). Wavelength maxima and extinction coefficients are item‑ and solvent‑dependent; check CoA before quantitative use.
• Hygroscopicity/polymorphism: Not specified for this item; refer to CoA/Spec Sheet.
• Notes for handling solutions (general): Filter sterilize only if required for cell work (0.22 µm PTFE for DMSO solutions). Avoid aqueous buffers containing nucleophiles if instability is suspected; prepare fresh aliquots to minimize degradation.

Quality and Grades

• Grade/purity: Not specified for this item; refer to CoA/Spec Sheet for assay method (e.g., HPLC/LC–MS) and purity threshold.
• What grade implies (general): Screening/probe‑grade small molecules are typically provided at high chemical purity with controlled identity (NMR/HRMS/HPLC) to support reproducible biological experiments. If an HPLC grade or “≥98%” purity is indicated on the CoA, it generally reflects main‑component purity by area % under a stated chromatographic method.
• Counter‑ion/salt form: Bioactivity and solubility can differ between free base/neutral form and sodium salt. The specific form sold under this SKU should be confirmed from the CoA; prepare stocks accordingly.
• Stabilizers: None specified for this item. If stabilizers/antioxidants are present, they will be declared on the CoA as they may impact analytical readouts.
• Documentation provided: CoA typically includes identity data (e.g., MS, NMR), chromatographic purity, water content (Karl Fischer) if relevant, and residual solvent profile. For any parameter not listed here, see the current lot CoA/Spec Sheet.

Reaction and Applications

This product is a bioactive small molecule used as a research tool rather than as a synthetic reagent. As such, classical synthetic “reaction applications” (e.g., cross‑couplings, Grignard reactions) are not typically applicable.

• Research applications (literature, general):
  • Employed as a chemical probe to interrogate mitotic and RAS‑related signaling pathways in cells.
  • Utilized in target validation, phenotypic screening, and chemical biology studies to modulate kinase‑associated pathways.
• Practical assay considerations:
  • Prepare concentrated DMSO stocks and dispense using positive‑displacement or acoustic dispensing for HTS.
  • Include vehicle controls matched for DMSO percentage and time‑course.
  • Consider lot‑to‑lot verification by LC–MS or HPLC in your lab for critical experiments.
• Analytics:
  • Monitor compound stability in assay media over the assay time by LC–MS when possible (general best practice).
  • If fluorescence readouts are used, check for inner‑filter effects or compound auto‑fluorescence due to aromatic chromophores (general).

Reaction Conditions

Conventional synthetic reaction conditions are not applicable to this catalog item since it is used as a research probe rather than as a reagent. For biological assays, the following general handling “conditions” apply (literature/general):

• Stock preparation: Dissolve in anhydrous DMSO to prepare a concentrated stock (e.g., 10–50 mM, as solubility allows). Filter if required through 0.22 µm PTFE.
• Dosing: Dilute into pre‑warmed culture medium or assay buffer to achieve the desired final concentration with typical DMSO carryover ≤0.1–0.5% v/v, maintaining constant vehicle across controls.
• Temperature and light: Handle at ambient temperature during setup; protect from strong light. Return aliquots promptly to low temperature storage to limit degradation.
• Stability checks: Verify stability in the chosen medium over the assay duration by LC–MS/HPLC when results are sensitive to compound loss or conversion.
• Replicates and controls: Include vehicle controls, time‑matched controls, and preferably an orthogonal pathway probe for benchmarking.

Safety and Handling

• GHS classification, pictograms, signal word, H‑statements: Not specified for this item; refer to the SDS for authoritative hazard information.
• General hazards (literature/general for bioactive small molecules): May cause irritation to skin, eyes, and respiratory tract. Bioactive small molecules should be handled as potentially toxic; avoid inhalation and ingestion.
• PPE: Laboratory coat, safety glasses, and appropriate chemically resistant gloves (e.g., nitrile). Use in a certified chemical fume hood or ventilated enclosure when weighing powders or preparing solutions.
• Storage incompatibilities: Keep away from strong oxidizers and bases/acids unless compatibility is known (general). Protect solutions from light if chromophore is present (literature, general practice).
• Special risks: For DMSO stock solutions, avoid skin contact—DMSO can enhance dermal absorption of solutes. If the compound has conjugated/aromatic functionalities, photooxidation may occur; minimize light exposure (general guidance).
• First‑aid overview (general):
  • Skin: Wash with soap and water; remove contaminated clothing.
  • Eyes: Rinse cautiously with water for several minutes; remove contact lenses if easy.
  • Inhalation: Move to fresh air; seek medical attention if symptoms occur.
  • Ingestion: Rinse mouth; seek medical attention.
• Spill/cleanup: Avoid dust generation. Absorb solutions with inert material; dispose per institutional and local regulations.
• Always consult the product’s SDS for definitive safety and regulatory guidance.

Solvent Selection

• Primary stock solvent (general, literature): DMSO is most commonly used for rigosertib and similar aromatic sulfone probes due to favorable solubility and stability.
• Alternative solvents (general): DMF, NMP, or ethanol may dissolve the compound; aqueous buffers may require co‑solvent (DMSO 0.1–1% v/v in final assay) or pH adjustment depending on salt form.
• Miscibility and handling tips:
  • Ensure complete dissolution before dilution into aqueous media to avoid precipitation and variable exposure levels.
  • Warm gently (room temperature) and vortex/sonicate as needed; avoid prolonged heating.
• Selection guidance:
  • Choose DMSO for high‑concentration master stocks (e.g., 10–50 mM) for HTS or cell‑based assays (general guidance).
  • For in vitro enzyme assays sensitive to DMSO, explore lower DMSO carryover (≤0.1%) or use mixed solvents (e.g., 10–20% PEG‑400 + water) if compatible (general).
• Compatibility notes (general): Avoid strong nucleophiles or highly basic media unless stability is verified. Use amber vials to limit light exposure of conjugated compounds.

Storage and Reconstitution

• Storage conditions (item‑specific): Store at −80°C (per Product Data). Protect from light and moisture.
• Shipping (item‑specific): Shipped on dry ice packs + cold packs (per Product Data) to maintain low temperature during transit.
• In‑lab handling:
  • Let sealed containers warm gradually to room temperature in a desiccator before opening to minimize moisture condensation.
  • Reseal promptly under dry inert atmosphere if possible.
• Reconstitution (general guidance for small molecules):
  • Dissolve in anhydrous DMSO to prepare a concentrated stock (e.g., 10–50 mM, subject to actual solubility for this item). Mix thoroughly to ensure complete dissolution.
  • Optional: Pass through a 0.22 µm PTFE filter if particulate is present.
• Aliquoting and stability (general):
  • Prepare single‑use aliquots to avoid repeated freeze–thaw. Store aliquots at −80°C in amber vials or light‑protective tubes.
  • For working solutions in aqueous media, use immediately or within the time window validated by your internal stability testing.
• Note: For any parameter not specified above (e.g., aqueous solubility, exact shelf life), consult the lot‑specific CoA/Spec Sheet and SDS. Research use only.

Structure and Identity

• Product name: Rigosertib (ON-01910); also known in literature as ON 01910 or rigosertib sodium for its sodium salt form (literature; salt form not specified for this item).
• CAS: 1225497-78-8 (assigned to rigosertib; literature).
• Category: Small molecule screening compound (per Category Path: 小分子和化合物库).
• 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 (literature, general): Rigosertib is reported to be an aromatic sulfone–containing small molecule with conjugated aryl–alkenyl substructures. The sodium salt is an anionic sulfonylate; the free base/neutral form bears a sulfone. Exact substitution pattern and stereochemistry should be confirmed from the certificate of analysis for this specific lot.
• 2D structural description (literature, general): Consists of two aromatic rings connected through an ethenyl (styryl-like) linker, with a sulfone functional group appended to one ring; additional heteroatoms are present in side chains. Please verify the exact atom connectivity for this catalog item from the official specification.

Synthetic Utility

This product is a finished bioactive small molecule and is not commonly used as a building block or reagent in multistep synthesis. Therefore, classical synthetic utility (e.g., as a coupling partner or functional group donor) is not typically applicable.

• If derivatization is desired for probe development (general):
  • Structure–activity relationship (SAR) campaigns reported in literature have explored modifications to the aryl and sulfone regions. Any derivatization should be guided by published SAR and confirmed by biological testing.
  • Prodrug or salt‑form exploration may be considered to tune solubility for research; ensure rigorous analytical characterization (NMR, HRMS, HPLC).
• Analytical chemistry relevance:
  • Serves as a positive control or reference analyte for LC–MS method development, stability‑indicating methods, and impurity profiling in research environments.

Target Specificity

• Item‑specific target data: Not specified for this item; refer to CoA/Spec Sheet and current literature for mechanistic details.
• Literature context (general, for background only): Rigosertib has been reported as a modulator of mitotic kinase signaling (often associated with PLK1 pathways) and as a RAS‑mimetic that disrupts RAS–effector interactions. Specific binding partners, Kd values, and selectivity panels should be obtained from peer‑reviewed sources and verified experimentally in your system.