Rigosertib

SKU: orb1307796

Description

Rigosertib (ON-01910) is a potent, non-ATP-competitive PLK1 inhibitor (IC50: 9 nM) and multi-kinase inhibitor that induces apoptosis via PI3K/Akt pathway inhibition, promotes histone H2AX phosphorylation, and causes G2/M cell cycle arrest. It has demonstrated anti-tumor activity in both in vitro and in vivo cancer research models, including studies in myelodysplastic syndromes.

Research Area

Cardiovascular Research, Cell Biology, Signal Transduction

Key Properties

• CAS Number: 592542-59-1
• MW: 451.49
• Purity: 99.53%
• Formula: C₂₁H₂₅NO₈S
• SMILES: C(=C/S(CC1=CC(NCC(O)=O)=C(OC)C=C1)(=O)=O)\C2=C(OC)C=C(OC)C=C2OC
• Target: Src,Bcr-Abl,FLT,PI3K,PDGFR,PLK,CDK,Apoptosis
• Solubility: DMSO:75 mg/mL (166.12 mM);10% DMSO+40% PEG300+5% Tween 80+45% Saline:2 mg/mL (4.43 mM)

Bioactivity

• Target IC50:
  FLK1:42 nM|CDK1:260 nM|Fyn:182 nM|PDGFR:18 nM|BCR-ABL:32 nM|PLK2:260 nM|PLK1:9 nM|Src:155 nM
• In Vivo:
  Rigosertib (200 mg/kg, i.p.) displays inhibition on tumor growth in a mouse xenograft model of BT20 cells. Rigosertib (250 mg/kg, i.p.) markedly suppresses tumor growth in mouse xenograft models of Bel-7402, MCF-7, and MIA-PaCa cells .
• In Vitro:
  Rigosertib is a non-ATP-competitive inhibitor of PLK1 (IC50: 9 nM). Rigosertib displays cell killing activity against 94 different tumor cell lines (IC50: 50-250 nM), including BT27, MCF-7, DU145, PC3, U87, A549, H187, RF1, HCT15, SW480, and KB cells. Rigosertib also shows inhibition of PLK2, PDGFR, Flt1, BCR-ABL, Fyn, Src, and CDK1 (IC50: 18-260 nM). 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. Rigosertib also inhibits several multidrug-resistant tumor cell lines, including MES-SA, MES-SA/DX5a, CEM, and CEM/C2a (IC50: 50-100 nM). Rigosertib (100-250 nM) causes spindle abnormalities and apoptosis in HeLa cells. Rigosertib (0.25-5 μM) blocks cell cycle progression in G2/M phase in DU145 cells, causes an accumulation of cells containing subG1 content of DNA and activates apoptotic pathways. Rigosertib (50 nM-0.5 μM) induces loss of viability and caspase 3/7 activation in A549 cells. Rigosertib sodium (2 μM) induces apoptosis in chronic lymphocytic leukemia (CLL) cells without toxicity against T-cells or normal B-cells. Rigosertib sodium (2 μM) also abrogates the pro-survival effect of follicular dendritic cells on CLL cells and reduces the SDF-1-induced migration of leukemic cells.

Storage & Handling

• Storage: Powder: -20°C for 3 years | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

Cdk1, Apoptosis, BCR-ABL, BcrAbl, Inhibitor, Flt1, Fyn, ON01910, ON-01910, ON 01910, PLK1, PLK, PLK2, inhibit, Src, Rigosertib, Polo-like Kinase (PLK), PDGFR, Phosphoinositide 3-kinase, PI3K

Compound Identifiers

PubChem CID

6918736