| Identification | Back Directory | [Name]
7-(5-(1,5-dichloropentan-3-yl)-1-Methyl-1H-benzo[d]iMidazol-2-yl)-N-hydroxyheptanaMide | [CAS]
1236199-60-2 | [Synonyms]
CS-2555
EDO-S101
Minomustine
Tinostamustine(EDO-S101)
EDO-S101;EDO S101;EDOS101
1H-Benzimidazole-2-heptanamide, 5-[bis(2-chloroethyl)amino]-N-hydroxy-1-methyl-
7-{5-[bis(2-chloroethyl)amino]-1-methyl-1H-1,3-benzodiazol-2-yl}-N-hydroxyheptanamide
7-(5-(bis(2-chloroethyl)amino)-1-methyl-1H-benzo[d]imidazol-2-yl)-N-hydroxyheptanamide
7-(5-(1,5-dichloropentan-3-yl)-1-Methyl-1H-benzo[d]iMidazol-2-yl)-N-hydroxyheptanaMide | [Molecular Formula]
C19H28Cl2N4O2 | [MDL Number]
MFCD29037367 | [MOL File]
1236199-60-2.mol | [Molecular Weight]
415.36 |
| Chemical Properties | Back Directory | [density ]
1.27±0.1 g/cm3(Predicted) | [storage temp. ]
Keep in dark place,Inert atmosphere,2-8°C | [solubility ]
DMSO:14.0(Max Conc. mg/mL);33.71(Max Conc. mM)
Ethanol:2.0(Max Conc. mg/mL);4.82(Max Conc. mM) | [form ]
A crystalline solid | [pka]
9.48±0.20(Predicted) | [color ]
White to off-white |
| Hazard Information | Back Directory | [Description]
EDO-S101 is a fusion molecule composed of the DNA alkylating agent bendamustine and the histone deacetylase (HDAC) inhibitor SAHA 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. | [Uses]
Tinostamustine (EDO-S101) is a pan HDAC inhibitor; inhibits HDAC6, HDAC1, HDAC2 and HDAC3 with IC50 values of 6 nM, 9 nM, 9 nM and 25 nM, respectively[1]. | [in vivo]
Intracellular HDAC inhibition of Tinostamustine, which occurs rapidly after dosing is at maximum activity already at the lowest dose of 10mg/kg and lasts for about 12-16 hours. Exposure to Tinostamustine causes a strong DNA repair response evidenced by activation of pH2AX and p53 in tumors taken from mice bearing subcutaneous human Burkitt’s lymphoma. Tumors of BL rapidly shrink or are completely eradicated after i.v. administration of Tinostamustine[1]. | [IC 50]
HDAC6: 6 nM (IC50); HDAC1: 9 nM (IC50); HDAC2: 9 nM (IC50); HDAC3: 25 nM (IC50); HDAC10: 72 nM (IC50); HDAC8: 107 nM (IC50) | [References]
[1] Mehrling T, et al. The Alkylating-HDAC Inhibition Fusion Principle: Taking Chemotherapy to the Next Level with the First in Class Molecule EDO-S101. Anticancer Agents Med Chem. 2016;16(1):20-8. DOI:10.2174/1871520615666150518092027 |
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| Company Name: |
Acesys Pharmatech
|
| Telephone: |
18860950986 |
| Website: |
www.chemicalbook.com/ShowSupplierProductsList15849/0_EN.htm |
| Company Name: |
Twochem Co.Ltd.
|
| Telephone: |
021-58111628 15800915896 |
| Website: |
cn.twochem.com |
|