| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| Targets |
HSP70
MKT-077 targets mitochondria and heat shock protein 70 (Hsp70). As a cationic rhodacyanine dye, it accumulates in mitochondria due to its positive charge and lipophilic properties. It also inhibits Hsp70, a molecular chaperone involved in protein folding and cell survival. By targeting these cellular components, MKT-077 disrupts mitochondrial function and protein homeostasis, leading to antiproliferative effects. |
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| 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.
MKT-077 demonstrates potent in vitro antiproliferative activity against a broad spectrum of human cancer cell lines, including colon, breast, and pancreatic cancer. It exhibits EC50s of 1.4-2.2 µM in vitro. The compound has low cytotoxicity, suggesting that it selectively targets cancer cells. Its activity is attributed to its mitochondrial accumulation and Hsp70 inhibition. |
| 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 ].
MKT-077 inhibits tumor growth in nude mouse xenograft models. This demonstrates its in vivo efficacy as an antitumor agent. The compound's ability to accumulate in mitochondria and inhibit Hsp70 contributes to its antitumor effects in vivo. Its low cytotoxicity profile makes it a potentially promising anticancer agent. |
| Enzyme Assay |
MKT-077 does not have a typical enzyme/receptor binding assay. Its activity is assessed in cell-based assays that measure its antiproliferative effects on cancer cell lines. Cells are treated with the compound, and cell viability is measured using assays such as MTT or CellTiter-Glo. The EC50 values are determined from dose-response curves.
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| Cell Assay |
In vitro cellular assays for MKT-077 involve treating cancer cell lines with the compound and measuring cell viability. The compound's effects on mitochondrial function can also be assessed by measuring mitochondrial membrane potential or ATP levels. Its ability to inhibit Hsp70 can be confirmed by measuring the expression of Hsp70 target genes or by assessing protein aggregation.
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| Animal Protocol |
In vivo animal experiments for MKT-077 involve administering the compound to nude mice bearing human tumor xenografts. Tumor growth is monitored, and the compound's ability to inhibit tumor growth is assessed. The compound's toxicity and pharmacokinetic properties are also evaluated in these studies.
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| ADME/Pharmacokinetics |
MKT-077 has a molecular weight of 432.0 and a molecular formula of C21H22ClN3OS2. It is highly water-soluble, which is a favorable property for pharmaceutical development. The compound is soluble in DMSO. Its pharmacokinetic properties, such as half-life and tissue distribution, would have been characterized in preclinical studies. Its fluorescence properties allow for tracking its distribution in cells and tissues.
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| Toxicity/Toxicokinetics |
The toxicological profile of MKT-077 is not extensively detailed in the provided sources. The compound is described as having low cytotoxicity, suggesting a favorable safety profile. However, as a mitochondrial-targeting agent, it may have potential off-target effects on normal cells. Its safety would need to be thoroughly evaluated in preclinical studies.
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| References |
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| Additional Infomation |
Rhodanine analogue MKT-077 is a synthetic heterocyclic pyridine compound. MKT-077 is a water-soluble, lipophilic cationic molecule and an analogue of rhodanine dyes. It can enter the mitochondria of tumor cells and is believed to act as a metabolic toxin in the mitochondria, leading to G1 phase arrest and apoptosis. This compound also exhibits selective cytotoxicity against cancer cells, the mechanism of which is through binding to the HSP70 family protein MOT-2 and reactivating the function of the tumor suppressor p53.
MKT-077 is a highly water-soluble cationic rhodacyanine dye with significant antitumor activity. It targets mitochondria and inhibits Hsp70. The compound exhibits antiproliferative activity against a broad spectrum of cancer cell lines with EC50s of 1.4-2.2 µM. It has been shown to inhibit tumor growth in nude mouse xenograft models. MKT-077 is available from various chemical suppliers for research purposes. |
| Molecular Formula |
C21H22CLN3OS2
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|---|---|
| Molecular Weight |
431.99
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| Exact Mass |
431.089
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| Elemental Analysis |
C, 58.39; H, 5.13; Cl, 8.21; N, 9.73; O, 3.70; S, 14.84
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| CAS # |
147366-41-4
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| Related CAS # |
147366-41-4
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| PubChem CID |
6444403
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| Appearance |
Brown to reddish brown solid powder
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| LogP |
0.191
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
28
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| Complexity |
647
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| Defined Atom Stereocenter Count |
0
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| 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
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| InChi Key |
VSKYOTRJSLYFHX-UXJRWBAGSA-M
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| 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+;
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| 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
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| Synonyms |
MKT-077; MKT077; FJ 776; FJ776; FJ-776; MKT 077;
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| HS Tariff Code |
2934.99.03.00
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| 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)
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| Solubility (In Vitro) |
Water : 86 mg/mL
DMSO : 13~56.7 mg/mL (30.1~131.2 mM) Ethanol : 10 mg/mL |
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| 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 |
*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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