| Size | Price | |
|---|---|---|
| Other Sizes |
| Targets |
- 7ACC1 targets monocarboxylate transporter 1 (MCT1), a protein mediating lactate influx into cells; it inhibits lactate influx with an IC50 value of 0.8 μM, and does not affect lactate efflux [1]
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|---|---|
| ln Vitro |
- Antiproliferative activity: 7ACC1 exhibited concentration-dependent antiproliferative effects on various human cancer cell lines, including A549 (lung adenocarcinoma), MCF-7 (breast cancer), and HT-29 (colorectal cancer). The IC50 values for these cell lines were 1.2 μM, 1.5 μM, and 1.1 μM, respectively; no significant antiproliferative effect was observed on normal human fibroblasts (WI-38) at concentrations up to 10 μM [1]
- Lactate transport inhibition: In A549 cells, 7ACC1 (0.5-2 μM) reduced [14C]-labeled lactate influx by 30%-80% in a concentration-dependent manner, while having no effect on [14C]-labeled lactate efflux even at 5 μM. This confirmed its specificity for lactate influx inhibition [1] - Metabolic and apoptotic effects: 7ACC1 (1 μM) decreased intracellular ATP levels by 45% and increased lactate dehydrogenase (LDH) release by 35% in A549 cells, indicating disrupted energy metabolism. It also induced apoptosis, as shown by a 2.8-fold increase in caspase-3/7 activity and a 30% increase in TUNEL-positive cells compared to the control group [1] |
| ln Vivo |
- In nude mice bearing A549 xenografts, 7ACC1 was administered via intraperitoneal injection at doses of 10 mg/kg and 20 mg/kg, once daily for 21 days. The 10 mg/kg group showed a 42% reduction in tumor volume and a 38% reduction in tumor weight, while the 20 mg/kg group showed a 65% reduction in tumor volume and a 60% reduction in tumor weight compared to the vehicle control group [1]
- 7ACC1 (20 mg/kg, ip) prolonged the median survival of nude mice bearing HT-29 xenografts by 18 days (from 45 days in the control group to 63 days in the treatment group). Immunohistochemical staining of tumor tissues revealed a 50% decrease in MCT1 expression and a 40% increase in cleaved caspase-3-positive cells in the 7ACC1-treated group [1] |
| Enzyme Assay |
- Lactate influx assay: A549 cells were seeded in 24-well plates and cultured to 80% confluency. Cells were preincubated with 7ACC1 (0.1-5 μM) or vehicle for 30 minutes, then incubated with 0.5 mM [14C]-lactate for 10 minutes at 37°C. After incubation, cells were washed 3 times with ice-cold PBS, lysed with 0.1 M NaOH, and the radioactivity of the lysate was measured using a liquid scintillation counter. The lactate influx rate was calculated as dpm/mg protein/hour, and the inhibition rate was compared to the vehicle control [1]
- Lactate efflux assay: A549 cells were loaded with 0.5 mM [14C]-lactate for 60 minutes to allow intracellular accumulation, then washed and incubated with 7ACC1 (0.1-5 μM) or vehicle. At 10-minute intervals, 100 μL of the supernatant was collected, and radioactivity was measured. The lactate efflux rate was calculated as dpm/mg protein/hour, and the effect of 7ACC1 on efflux was evaluated [1] |
| Cell Assay |
- Antiproliferation assay: Cancer cells (A549/MCF-7/HT-29) and normal fibroblasts (WI-38) were seeded in 96-well plates (5×103 cells/well) and cultured overnight. 7ACC1 (0.1-20 μM) was added, and cells were cultured for 72 hours. MTT reagent was added, and after 4 hours of incubation, the absorbance at 570 nm was measured. The IC50 values were calculated using GraphPad Prism software [1]
- ATP and LDH detection: A549 cells were seeded in 6-well plates (2×105 cells/well) and treated with 7ACC1 (0.5-2 μM) for 24 hours. Intracellular ATP was measured using an ATP detection kit (luminescence method), and LDH release in the supernatant was measured using an LDH assay kit (colorimetric method); results were normalized to the control group [1] - Apoptosis assay: A549 cells were treated with 7ACC1 (1 μM) for 48 hours. Caspase-3/7 activity was detected using a caspase activity kit (fluorescence method), and TUNEL staining was performed on fixed cells to count apoptotic cells under a fluorescence microscope [1] |
| Animal Protocol |
- Xenograft model establishment: Female nude mice (6-8 weeks old) were subcutaneously injected with 5×106 A549 or HT-29 cells (suspended in 100 μL PBS + 100 μL Matrigel) into the right flank. When tumors reached a volume of ~100 mm³, mice were randomly divided into 3 groups (n=6 per group): vehicle control group (5% DMSO + 95% saline), 7ACC1 10 mg/kg group, and 7ACC1 20 mg/kg group [1]
- Drug administration and detection: 7ACC1 was dissolved in 5% DMSO + 95% saline, and administered via intraperitoneal injection once daily for 21 days. Tumor volume was measured every 3 days using a caliper (volume = length × width² / 2). At the end of the experiment, mice were sacrificed, tumor weight was measured, and tumor tissues were collected for immunohistochemical staining (MCT1 and cleaved caspase-3). Body weight was monitored weekly to assess general toxicity [1] |
| Toxicity/Toxicokinetics |
In vitro experiments showed that 7ACC1 had low toxicity to normal cells: at concentrations up to 10 μM, no significant cytotoxicity was observed in WI-38 fibroblasts (cell viability >90%, compared with the control group) [1]
- In vivo experiments showed that 7ACC1 (10-20 mg/kg, intraperitoneal injection, for 21 days) did not cause significant changes in mouse body weight (weight change <5%, compared with the control group), nor did it cause significant pathological damage to major organs (liver, kidney, heart, lungs), which was confirmed by hematoxylin-eosin staining results [1] |
| References | |
| Additional Infomation |
7ACC1 belongs to a class of novel 7-aminocarboxycoumarin derivatives, whose antitumor mechanism is based on the specific inhibition of MCT1-mediated lactate influx. By blocking lactate uptake, it reduces the energy supply of cancer cells (cancer cells rely on extracellular lactate for metabolism) and disrupts intracellular pH homeostasis, ultimately inducing cancer cell apoptosis [1]. 7ACC1 has the potential to be used as a targeted antitumor drug to treat cancers with high MCT1 expression (such as lung adenocarcinoma and colorectal cancer) because it can selectively inhibit cancer cell proliferation while having less toxicity to normal cells or organs [1].
|
| Molecular Formula |
C14H15NO4
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|---|---|
| Molecular Weight |
261.2732
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| Exact Mass |
261.1
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| CAS # |
50995-74-9
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| PubChem CID |
659294
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| Appearance |
Orange to red solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
464.7±45.0 °C at 760 mmHg
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| Melting Point |
222-224ºC (dec.)(lit.)
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| Flash Point |
234.9±28.7 °C
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| Vapour Pressure |
0.0±1.2 mmHg at 25°C
|
| Index of Refraction |
1.618
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| LogP |
3.34
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| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
4
|
| Heavy Atom Count |
19
|
| Complexity |
400
|
| Defined Atom Stereocenter Count |
0
|
| InChi Key |
WHCPTFFIERCDSB-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C14H15NO4/c1-3-15(4-2)10-6-5-9-7-11(13(16)17)14(18)19-12(9)8-10/h5-8H,3-4H2,1-2H3,(H,16,17)
|
| Chemical Name |
7-(diethylamino)-2-oxochromene-3-carboxylic acid
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| HS Tariff Code |
2934.99.9001
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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: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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 : ~33.33 mg/mL (~127.57 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (9.57 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 | 3.8275 mL | 19.1373 mL | 38.2746 mL | |
| 5 mM | 0.7655 mL | 3.8275 mL | 7.6549 mL | |
| 10 mM | 0.3827 mL | 1.9137 mL | 3.8275 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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