Physicochemical Properties
| Molecular Formula | C21H22CLN3OS2 |
| Molecular Weight | 431.99 |
| Exact Mass | 431.089 |
| Elemental Analysis | C, 58.39; H, 5.13; Cl, 8.21; N, 9.73; O, 3.70; S, 14.84 |
| CAS # | 147366-41-4 |
| Related CAS # | 147366-41-4 |
| PubChem CID | 6444403 |
| Appearance | Brown to reddish brown solid powder |
| LogP | 0.191 |
| Hydrogen Bond Donor Count | 0 |
| Hydrogen Bond Acceptor Count | 5 |
| Rotatable Bond Count | 3 |
| Heavy Atom Count | 28 |
| Complexity | 647 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | [Cl-].S1/C(=C(/[H])\C2=C([H])C([H])=C([H])C([H])=[N+]2C([H])([H])C([H])([H])[H])/N(C([H])([H])C([H])([H])[H])C(C1=C1N(C([H])([H])[H])C2=C([H])C([H])=C([H])C([H])=C2S1)=O |
| InChi Key | VSKYOTRJSLYFHX-UXJRWBAGSA-M |
| InChi Code | InChI=1S/C21H22N3OS2.ClH/c1-4-23-13-9-8-10-15(23)14-18-24(5-2)20(25)19(27-18)21-22(3)16-11-6-7-12-17(16)26-21;/h6-14H,4-5H2,1-3H3;1H/q+1;/p-1/b21-19+; |
| Chemical Name | (2Z,5E)-3-ethyl-2-[(1-ethylpyridin-1-ium-2-yl)methylidene]-5-(3-methyl-1,3-benzothiazol-2-ylidene)-1,3-thiazolidin-4-one;chloride |
| Synonyms | MKT-077; MKT077; FJ 776; FJ776; FJ-776; MKT 077; |
| HS Tariff Code | 2934.99.03.00 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| Targets | HSP70 |
| ln Vitro | Preparation of MKT-077 solution 1.1 Preparation of stock solution Dissolve 1 milligram MKT-077 in 0.2315 mL DMSO to yield 10 mM MKT-077. Note: It is advised that the stock solution be stored at -20°C or -80°C away from light. Preparation of 1.2 MKT-077 functional solution. Use serum-free cell diluent or PBS to take 5-10 μM MKT-077 working solution. Note: Please adjust the concentration of MKT-077 working fluid according to the real conditions. Staining 2.1 Cell preparation. Suspension cells: Centrifuge at 1000 g for 3-5 minutes at 4°C and discard the supernatant. Wash twice with PBS, 5 minutes each time. Adherent cells: Discard the cell culture medium and add islet dissociated cells to produce a single cell suspension. Centrifuge at 1000g for 3-5 minutes at 4°C and discard the supernatant. Wash twice with PBS, 5 minutes each time. 2.2 Add 1 mL MKT-077 working solution and pre-working solution for 30 minutes. 2.3 Centrifuge at 400 g for 3-4 minutes at 4°C and discard the supernatant. 2.4 Wash twice with PBS, 5 minutes each time. 2.5 Resuspend cells in serum-free cell culture media or PBS and detect with fluorescence microscopy or flow cytometer. |
| ln Vivo | Systemic dormancy of MKT-077 greatly inhibited the growth of mouse TT xenografts throughout therapy. At the completion of MKT-077 treatment, the tumor weight in the MKT-077-treated group was determined to be nearly two times lower than that of the head. MKT-077 administration also leads in weight loss and overall toxicity in rats [1]. The results demonstrated that succinate-induced, ADP-stimulated respiratory rhythms in mitochondria separated from transplants given with a daily bolus injection of 15 mg MKT-077 at 1 kg body weight for 5 days were considerably lower than those in untreated cells [3 ]. |
| References |
[1]. Selective Mitochondrial Uptake of MKT-077 Can Suppress Medullary Thyroid Carcinoma Cell Survival In Vitro and In Vivo. Endocrinol Metab (Seoul). 2015 Dec;30(4):593-603. [2]. Analogs of the Allosteric Heat Shock Protein 70 (Hsp70) Inhibitor, MKT-077, as Anti-Cancer Agents. ACS Med Chem Lett. 2013 Nov 14;4(11).. [3]. Selective Mitochondrial Uptake of MKT-077 Can Suppress Medullary Thyroid Carcinoma Cell Survival In Vitro and In Vivo. Endocrinol Metab (Seoul). 2015 Dec;30(4):593-603. [4]. Analogs of the Allosteric Heat Shock Protein 70 (Hsp70) Inhibitor, MKT-077, as Anti-Cancer Agents. ACS Med Chem Lett. 2013 Nov 14;4(11). [5]. In vivo administration of MKT-077 causes partial yet reversible impairment of mitochondrial function. Cancer Res. 1996 Feb 1;56(3):551-5. |
| Additional Infomation | Rhodacyanine Analog MKT-077 is a synthetic heterocyclic pyridinium compound. MKT-077 is a water soluble lipophilic cationic molecule and an analog of rhodacyanine dye, which partitions into tumor cell mitochondria where it is thought to act as a metabolic poison, leading to G1 arrest and apoptosis. This agent also shows selective cytotoxicity to cancer cells mediated by its binding to the hsp70 family protein mot-2 and reactivation of tumor suppressor p53 function. |
Solubility Data
| Solubility (In Vitro) |
Water : 86 mg/mL DMSO : 13~56.7 mg/mL (30.1~131.2 mM) Ethanol : 10 mg/mL |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 4.25 mg/mL (9.84 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 42.5 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. Solubility in Formulation 2: 4.25 mg/mL (9.84 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 42.5 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline 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 | 2.3149 mL | 11.5743 mL | 23.1487 mL | |
| 5 mM | 0.4630 mL | 2.3149 mL | 4.6297 mL | |
| 10 mM | 0.2315 mL | 1.1574 mL | 2.3149 mL |