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Purity: ≥98%
Tinostamustine (also known as EDO-S101; EDO-S 101; Minomustine) is a novel, potent, fisrt-in-class alkylating agent and pan histone-deacetylase (HDAC) inhibitor with anticancer activity. It inhibits HDAC1, HDAC2 and HDAC3 with IC50 values of 9, 9 and 25 nM, respectively and can also alkylate the DNA of cancer cells. Tinostamustine is an alkylatlng HDAC inhibitor and a fusion molecule comprising of the alkylator bendamustine and the HDAC-inhibitor vorinostat. It can potentiate the alkylating activity of the compound and/or may help to overcome resistance to other therapeutic agents. Tinostamustine was designed to allow for the exploitation of both mechanisms of action simultaneously with the goal to provide a molecule with superior efficacy over the single agents. The pharmacological testing confirms the full functional capacity of both moieties and encouraging pharmacological data raises the hope that the drug may turn out to be a great addition to the armentarium of anticancer agents.
| ln Vitro |
One hour after an intravenous injection of a dose of 10 mg/kg, tinostamustine reduced HDAC activity in rat peripheral blood mononuclear cells (PBMCs) by around 90% in cell tests; greater doses, up to 50 mg/kg, had no effect on HDAC activity in PBMCs. suppression of HDAC. Tinostustine exhibits strong anticancer activity and causes apoptosis in HL60 and Daudi cells. Initial in vitro tests using HL60 cells revealed that cleaving caspases 3, 9, and PARP triggered the intrinsic mechanism of apoptosis and markedly decreased the levels of the anti-apoptotic proteins XIAP and Mcl-1 [1].
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| ln Vivo |
Tenomustine has an intracellular HDAC inhibitory action that takes effect quickly after delivery, peaks at 10 mg/kg, and lasts for around 12 to 16 hours. Flavustine exposure triggers a potent DNA repair response, as evidenced by the activation of p53 and pH2AX in tumors from mice that had human Burkitt's lymphoma subcutaneously. Tinostamustine injections intravenously cause BL tumors to either rapidly shrink or disappear entirely [1].
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| 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
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| Molecular Formula |
C19H28CL2N4O2
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|---|---|
| Molecular Weight |
415.3572
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| CAS # |
1236199-60-2
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| Related CAS # |
1793059-58-1 (HCl);1236199-60-2;
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| SMILES |
O=C(NO)CCCCCCC1=NC2=CC(N(CCCl)CCCl)=CC=C2N1C
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| InChi Key |
GISXTRIGVCKQBX-UHFFFAOYSA-N
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| 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)
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| Chemical Name |
7-(5-(bis(2-chloroethyl)amino)-1-methyl-1H-benzo[d]imidazol-2-yl)-N-hydroxyheptanamide
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| Synonyms |
EDO-S101; Minomustine; EDO-S-101; EDO-S 101; EDO S-101;
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~240.76 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (6.02 mM) in 10% DMSO + 40% PEG300 +5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 + to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4076 mL | 12.0378 mL | 24.0755 mL | |
| 5 mM | 0.4815 mL | 2.4076 mL | 4.8151 mL | |
| 10 mM | 0.2408 mL | 1.2038 mL | 2.4076 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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