EDO-S101

EDO-S101 is a fusion molecule composed of the DNA alkylating agent bendamustine and the histone deacetylase (HDAC) inhibitor SAHA (Cay-10009929) that inhibits class I and II HDACs (IC50s = 9-107 nM for HDAC1-3, 6, 8, and 10). It inhibits HDAC activity in rat peripheral blood mononuclear cells (PBMCs) ex vivo by 90% following a single dose of 10 mg/kg. EDO-S101 also induces formation of DNA crosslinks and double-strand breaks in HL-60 cells. It reduces growth of multiple myeloma (MM) cell lines irrespective of p53 mutational status or established resistance to DNA alkylating agents (IC50s = 1.6-4.8 µM). EDO-S101 also induces MM cell death ex vivo in bone marrow samples isolated from patients with early- and late-stage MM. In vivo, EDO-S101 (60 mg/kg per week) reduces tumor growth and prolongs survival in an MM1S end-stage mouse xenograft model. It also prolongs survival in a multidrug resistant Vk12653 mouse transplant model of refractory MM.Formal Name: 5-[bis(2-chloroethyl)amino]-N-hydroxy-1-methyl-1H-benzimidazole-2-heptanamide. CAS Number: 1236199-60-2. Molecular Formula: C19H28Cl2N4O2. Formula Weight: 415.4. Purity: >98%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 1 mg/ml, DMSO: 5 mg/ml, DMSO:PBS (pH 7.2)(1:9): 0.1 mg/ml. lambdamax: 231, 324 nm. SMILES: CN1C2=CC=C(N(CCCl)CCCl)C=C2N=C1CCCCCCC(NO)=O. InChi Code: InChI=1S/C19H28Cl2N4O2/c1-24-17-9-8-15(25(12-10-20)13-11-21)14-16(17)22-18(24)6-4-2-3-5-7-19(26)23-27/h8-9,14,27H,2-7,10-13H2,1H3,(H,23,26). InChi Key: GISXTRIGVCKQBX-UHFFFAOYSA-N.