AdipoGen Life Sciences

Withaferin A

CHF 90.00
In stock
AG-CN2-0490-M0011 mgCHF 90.00
AG-CN2-0490-M0055 mgCHF 270.00
AG-CN2-0490-M01010 mgCHF 380.00
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Product Details
Synonyms NSC 101088; NSC 273757; 5β,6β-Epoxy-4β,22R,27-trihydroxy-1-oxo-δ-lactone-ergosta-2,24-dien-26-oic acid
Product Type Chemical
Properties
Formula

C28H38O6

MW 470.6
Merck Index 14: 10048
CAS 5119-48-2
RTECS KE7288500
Source/Host Chemicals Isolated from Withania somnifera.
Purity Chemicals ≥98% (HPLC)
Appearance White to off-white solid.
Solubility Soluble in DMSO (10mg/ml), DMF, 100% ethanol (5mg/ml), methanol (5mg/ml) or ethyl acetate. Insoluble in water.
InChi Key DBRXOUCRJQVYJQ-KUVJLYTASA-N
Smiles O=C1[C@@]2(C)[C@@]([C@H]3C[C@]4([H])C2CC[C@@]5(C)C4CC[C@@H]5[C@@H]([C@]6([H])OC(C(CO)=C(C)C6)=O)C)(O3)[C@@H](O)C=C1
Shipping and Handling
Shipping AMBIENT
Short Term Storage +4°C
Long Term Storage -20°C
Handling Advice Protect from light when in solution.
Use/Stability Stable for at least 2 years after receipt when stored at -20°C.
Stock solutions are stable for at least 3 months when stored at -20°C.
Documents
MSDS Download PDF
Product Specification Sheet
Datasheet Download PDF
Description
  • Multifunctional anticancer compound. Amplifies the cellular antioxidant and/or detoxification system, suppresses inflammatory pathways, selectively inhibits tumor cell proliferation and induces apoptosis, suppresses tumor angiogenesis, blocks epithelial-to-mesenchymal transition (EMT), tumor invasion and metastasis, alters tumor cell metabolism, induces immunomodulation and downregulates cancer stem cells targets.
  • Sensitizes resistant cancer cells to existing chemotherapeutic agents.
  • Antioxidant. Induces cytoprotective enzymes (Nrf2-dependent as well), including SOD, HO-1 (heme oxygenase-1), catalase, glutathione peroxidise, glutathione s-transferase and NQO1.
  • Anti-inflammatory agent. Inhibits COX-2 and iNOS expression (at protein and mRNA level) and PGE2 production. Prevents NF-κB activation by inhibiting activation of IKKβ. Inhibits Helicobacter pylori-induced IL-1β production by regulating NF-κB and directly inhibiting NLRP3 inflammasome activation.
  • Antiproliferative agent. Induces G2/M phase cell cycle arrest, targeting CDKs. Shown to modulate STAT3, Bcl2, Notch receptors, Akt, Hsp90, EGFR, HER2 and PCNA.
  • Disrupts the organization of microtubules and actin/microfilament. Stimulates F-actin cross-linking.
  • Induces tumor cell apoptosis. Shown to induce ROS production. Activates mitochondrial apoptosis pathway through Bcl-2 downregulation and Bax upregulation. Shown to induce p53-dependent pathways and ER-stress. Activates the tumor suppressor protein PAR-4. Directly or indirectly inhibits selected other kinases, such  MAPK or STAT3. Shown to inhibit hedgehog signalling pathway.
  • Described to be an autophagy inducer and inhibitor.
  • Potent inhibitor of the 20S proteasome β5 subunit chymotrypsin-like activity.
  • Potent angiogenesis inhibitor by modulating VEGF. Antimigratory, antiinvasive and antimetastatic compound. Targets TGF-β, vimentin, MMPs and Notch receptors.
  • Inhibits cancer stem cells targets, including aldehyde dehydrogenase 1 (ALDH1) activity. Alters cell line-specific the mRNA expression of cancer stem cell markers, such as Oct4, SOX-2, and Nanog.
  • Reported to induce neuronal regeneration.
  • Antidiabetic compound. Potent Leptin sensitizer, acting similar to Celastrol (Prod. No. AG-CN2-0460).
  • Covalent inhibitor of IPO5 (importin-5, also known as Ran-binding protein 5; RANBP5 or karyopherin β-3; KPNB3)
Product References
  1. Antitumor activity of withaferin A (NSC-101088): B. Shohat, et al.; Cancer Chemother. Rep. 51, 271 (1967)
  2. Withaferin A is a potent inhibitor of angiogenesis: R. Mohan, et al.; Angiogenesis 7, 115 (2004)
  3. Neuritic regeneration and synaptic reconstruction induced by withanolide: A: T. Kuboyama, et al.; Br. J. Pharmacol. 144, 961 (2005)
  4. The tumor proteasome is a primary target for the natural anticancer compound Withaferin A isolated from "Indian winter cherry": H. Yang, et al.; Mol. Pharmacol. 71, 426 (2007)
  5. The tumor inhibitor and antiangiogenic agent withaferin A targets the intermediate filament protein vimentin: P. Bargagna-Mohan, etal.; Chem. Biol. 14, 623 (2007)
  6. Withaferin A induces apoptosis by activating p38 mitogen-activated protein kinase signaling cascade in leukemic cells of lymphoid and myeloid origin through mitochondrial death cascade: C. Mandal, et al.; Apoptosis 13, 1450 (2008)
  7. Inhibition of monosodium urate crystal-induced inflammation by withaferin A: E.P. Sabina, et al.; J. Pharm. Pharm. Sci. 11, 46 (2008)
  8. Withaferin A targets heat shock protein 90 in pancreatic cancer cells: Y. Yu, et al.; Biochem. Pharmacol. 79, 542 (2010)
  9. Notch-1 inhibition by Withaferin-A: a therapeutic target against colon carcinogenesis: S. Koduru, et al.; Mol. Cancer Ther. 9, 202 (2010)
  10. Withaferin A inhibits activation of signal transducer and activator of transcription 3 in human breast cancer cells: J. Lee, et al.; Carcinogenesis. 31, 1991 (2010)
  11. Inhibition of the NEMO/IKKß association complex formation, a novel mechanism associated with the NF-kB activation suppression by Withania somnifera's key metabolite withaferin A: A. Grover, et al.; BMC Genomics 11, s25 (2010)
  12. Withaferin A induces apoptosis in human melanoma cells through generation of reactive oxygen species and down-regulation of Bcl-2: E. Mayola, et al.; Apoptosis 16, 1014 (2011)
  13. Withaferin a alters intermediate filament organization, cell shape and behavior: B. Grin, et al.; PLoS One 7, e39065 (2012)
  14. Withaferin A causes activation of Notch2 and Notch4 in human breast cancer cells: J. Lee, et al.; Breast Cancer Res. Treat. 136, 45 (2012)
  15. Molecular insight in the multifunctional activities of Withaferin A: W. Van den Berghe, et al.; Biochem. Pharmacol. 84, 1282 (2012) (Review)
  16. Inhibition of VEGF: a novel mechanism to control angiogenesis by Withania somnifera's key metabolite Withaferin A: S. Saha, et al.; In Silico Pharmacol. 1, 11 (2013)
  17. Withaferin A inhibits NF-kappaB activation by targeting cysteine 179 in IKKß: K. Heyninck, et al.; Biochem. Pharmacol. 91, 501 (2014)
  18. Withaferin A Inhibits Helicobacter pylori-induced Production of IL-1β in Dendritic Cells by Regulating NF-κB and NLRP3 Inflammasome Activation: J.E. Kim, et al.; Immune Netw. 15, 269 (2015)
  19. Molecular docking and dynamic simulation studies evidenced plausible immunotherapeutic anticancer property by Withaferin A targeting indoleamine 2,3-dioxygenase: S.V. Reddy, et al.; J. Biomol. Struct. Dyn. 33, 2695 (2015)
  20. Hedgehog inhibitors from Withania somnifera: T. Yoneyama, et al.; Bioorg. Med. Chem. Lett. 25, 3541 (2015)
  21. The Use of Withaferin A to study intermediate filaments: R. Mohan & P. Bargagna-Mohan; Methods Enzymol. 568, 187 (2016)
  22. Simultaneous inhibition of the ubiquitin-proteasome system and autophagy enhances apoptosis induced by ER stress aggravators in human pancreatic cancer cells: Autophagy 12, 1521 (2016)
  23. Withaferin A is a leptin sensitizer with strong antidiabetic properties in mice: J. Lee, et al.; Nat. Med. 22, 1023 (2016)
  24. Withaferin-A - A natural anticancer agent with pleitropic mechanisms of action: I.C. Lee & B.Y. Choi; Int. J. Mol. Sci. 17, 290 (2016) (Review)
  25. Withaferin A, a polyfunctional pharmacophore that includes covalent engagement of IPO5, is an inhibitor of influenza A replication: R. Patouret, et al.; Bioorg. Med. Chem. 69, 116883 (2022)
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