Isosilybin

SKU: orb1221842

Description

Isosilybin and Silybin might be suitable candidates to design potent PXR antagonists to prevent drug-drug interactions via CYP3A4 in cancer patients.

Key Properties

• CAS Number: 72581-71-6
• MW: 482.44
• Purity: >98% (HPLC)
• Formula: C₂₅H₂₂O₁₀
• SMILES: C1(C(C(=O)c2c(cc(cc2O1)O)O)O)c1cc2OC(C(Oc2cc1)c1cc(c(cc1)O)OC)CO
• Target: CYP3A4
• Solubility: DMSO : ≥ 28 mg/mL; 58.04 mM

Bioactivity

• In Vitro:
  The reporter gene assay shows that milk thistle’s components silybin and isosilybin are responsible for the inhibition of PXR-mediated CYP3A4 induction by milk thistle. Compared with silybin, its isomer isosilybin is a stronger inhibitor of PXR-mediated CYP3A4 induction. A solution of 89, 133, and 200 μM isosilybin significantly inhibits CYP3A4 induction by 64, 82, and 88%, respectively. Isosilybin inhibits CYP3A4 induction with an IC50 of 74 μM. Isosilybin B and isosilybin A, two diastereoisomers isolated from silymarin, have anti-prostate cancer (PCA) activity that is mediated via cell cycle arrest and apoptosis induction. Isosilybin B and isosilybin A treatment results in growth inhibition and cell death together with a strong G(1) arrest and apoptosis in human prostate cancer LNCaP and 22Rv1 cells. Isosilybin B causes increased phosphorylation of Akt (Ser-473 and Thr-308) and Mdm2 (Ser-166), which is linked with androgen receptor degradation as pretreatment with PI3K inhibitor (LY294002)-restored androgen receptor level. Isosilybin B treatment enhances the formation of complex between Akt, Mdm2 and AR, which promotes phosphorylation-dependent AR ubiquitination and its degradation by proteasome. Isosilybin A is able to significantly activate PPARγ at a concentration of 30 μM (2.08±0.48 fold, p<0.01). Isosilybin A causes transactivation of a PPARγ-dependent luciferase reporter in a concentration-dependent manner. In silico docking studies suggests a binding mode for 3 distinct from that of the inactive silymarin constituents, with one additional hydrogen bond to Ser342 in the entrance region of the ligand-binding domain of the receptor.

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

Isosilybinin

Quick Database Links

Gene Symbol

CYP3A4