Withaferin A

Withaferin A is a steroidal lactone that has been found in W. somnifera with diverse biological activities. It binds to and induces aggregation of vimentin intermediate filaments in cultured endothelial cells and fibroblasts, inducing apoptosis when used at concentrations ranging from 2 to 25 µM. It also induces formation of perinuclear aggregates in other intermediate filament networks including peripherin, neurofilament-triplet protein, and keratin as well as disrupts the organization of microtubules and actin/microfilaments. Withaferin A induces noncanonical ferroptosis via induction of lipid peroxidation through interaction with Kelch-like ECH-associated protein 1 (KEAP1) in IMR-32 neuroblastoma cells, an effect that is blocked by the ferroptosis inhibitors ciclopirox olamine and ferrostatin-1 (Cay-17729). It also binds to and inhibits glutathione peroxidase 4 (GPX4) in IMR-32 cells. In vivo, withaferin A (4 mg/kg) reduces intratumor GPX4 expression and induces tumor regression in an IMR-32 mouse xenograft model. Withaferin A (2 mg/kg) also inhibits angiogenesis in a mouse model of injury-induced corneal neovascularization.Formal Name: 5beta,6beta-epoxy-4beta,22R,27-trihydroxy-1-oxo-delta-lactone-ergosta-2,24-dien-26-oic acid. CAS Number: 5119-48-2. Synonyms: NSC 101088, NSC 273757. Molecular Formula: C28H38O6. Formula Weight: 470.6. Purity: >95%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 5 mg/ml, DMSO: 5 mg/ml, DMSO:PBS(pH7.2) (1:1): 0.5 mg/ml. lambdamax: 214 nm. SMILES: O=C/1O[C@H](CC(=C\1CO)\C)[C@@H](C)[C@H]6CC[C@@H]4[C@]6(C)CC[C@@H]3[C@]5(C(=O)\C=C/[C@H](O)[C@]52O[C@@H]2C[C@H]34)C. InChi Code: InChI=1S/C28H38O6/c1-14-11-21(33-25(32)17(14)13-29)15(2)18-5-6-19-16-12-24-28(34-24)23(31)8-7-22(30)27(28,4)20(16)9-10-26(18,19)3/h7-8,15-16,18-21,23-24,29,31H,5-6,9-13H2,1-4H3/t15-,16-,18+,19?,20-,21+,23-,24+,26+,27-,28+/m0/s1. InChi Key: DBRXOUCRJQVYJQ-NPRZOXALSA-N. Origin: Plant/Withania somnifera.