Romidepsin

Romidepsin, also known as FK228, is a natural bicyclic depsipeptide that, following reduction, selectively inhibits class I histone deacetylases (HDACs). Reduction of a disulfide bond on romidepsin within the cell generates a zinc-binding thiol, allowing potent and selective inhibition of HDAC1, 2, 3, and 8 (IC50s = 53, 39, 53, and 26 nM, respectively) over HDAC4, 6, 7, and 9 (IC50s = 470, 330, 3,200, and 12,000 nM, respectively). Through its effects on HDACs, romidepsin has anti-cancer activities, particularly against certain T cell lymphomas. Romidepsin also increases mRNA expression and nuclear protein levels of HDAC2, H3 acetylation and transcription of Grin2a, the gene for the NMDA receptor NR2A subunit, and protein levels of the NR2A subunit in the brain of Shank3-deficient mice, a model of autism. It also increases excitatory postsynaptic currents (EPSCs) in prefrontal cortex pyramidal neurons from Shank3-deficient mice. In addition, romidepsin rescues autism-like social deficits in Shank3-deficient mice for at least three weeks following administration of a 0.25 mg/kg per day dose for three days.Formal Name: cyclic (3->5)-disulfide-cyclo[(2Z)-2-amino-2-butenoyl-L-valyl-3S-hydroxy-7-mercapto-4E-heptenoyl-D-valyl-D-cysteinyl]. CAS Number: 128517-07-7. Synonyms: FK228, FR901228, NSC 630176. Molecular Formula: C24H36N4O6S2. Formula Weight: 540.7. Purity: >98%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 5 mg/ml, DMSO: 20 mg/ml, DMSO:PBS (pH 7.2) (1:1): 0.5 mg/ml, Ethanol: 10 mg/ml. SMILES: C/C=C(NC([C@@H](CSSCC/C=C/1)NC([C@@H](C(C)C)N2)=O)=O)/C(N[C@H](C(O[C@H]1CC2=O)=O)C(C)C)=O. InChi Code: InChI=1S/C24H36N4O6S2/c1-6-16-21(30)28-20(14(4)5)24(33)34-15-9-7-8-10-35-36-12-17(22(31)25-16)26-23(32)19(13(2)3)27-18(29)11-15/h6-7,9,13-15,17,19-20H,8,10-12H2,1-5H3,(H,25,31)(H,26,32)(H,27,29)(H,28,30)/b9-7+,16-6-/t15-,17-,19-,20+/m1/s1. InChi Key: OHRURASPPZQGQM-GCCNXGTGSA-N.