Product Name: Romidepsin(FK228)
Romidepsin(FK228) Chemical Structure
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A natural prodrug that inhibits Class I histone deacetylases (HDACs) (IC₅₀ values are: 36, 47, 510 and 14000 nM for HDAC1, HDAC2, HDAC4 and HDAC6, respectively). Displays potent anticancer activities.
Romidepsin(FK228) is a selective covalent Inhibitor of PI3Kα. Romidepsin(FK228) was tested against all four of the class I PI3K enzymes α, β, γ, and δ. In an end point assay, Romidepsin(FK228) potently inhibited PI3Kα and was 20−400 times less potent against β, γ, and δ. Romidepsin(FK228) inhibit PI3Kα signaling in cells and shows prolonged inhibition consistent with a covalent mechanism of Action. Romidepsin(FK228) inhibits growth of cells dependent on PI3Kα. Romidepsin(FK228) also inhibits PI3Kα signaling in vivo and bonds to p110α.
Romidepsin, also known as FK228 or depsipeptide, is potent and selective inhibitor of histone deacetylases (HDACs) which are associated with the regulation of re-expression of silenced tumor suppressor genes. It was the first HDAC inhibitor to manifest anti-tumor activity and originally isolated from a rod-shaped Gram-negative bacterium, Chromobacterium violaceum, found in a Japanese soil sample. Romidepsin exhibits a stronger inhibition towards HDAC1 and HDAC2 enzymes (class I), removing acetyl groups from the lysine residues of N-terminal histone tails and maintaining a more open and transcriptionally active chromatin state, than HDAC4 and HDAC6 enzymes (class II). Besides HDAC inhibition, romidepsin is also able to induce cell cycle arrest, cellular differentiation, apoptosis and alteration of gene expression in adult malignancies.
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