7ACC2
7ACC2, a carboxycoumarin derivative, is a potent inhibitor of monocarboxylate transporter 1 (MCT1), with an IC50 value of ~ 10 nM for lactate uptake in the human cervix carcinoma cell line SiHa. The family of MCT is composed of 14 members, among which only four isoforms (i.e. MCT1-4) have been documented to act as proton-linked transporters carrying short chain monocarboxylates such as lactate and pyruvate across cell membranes. In cancer cells, MCT1 and MCT4 are the most widely expressed, and MCT1 shows a better affinity for L-lactate than MCT4, enabling lactate entry into oxidative tumor cells. Thus, MCT1 blockade could serve as a potential therapeutic strategy to limit cancer progression. In addition, 7ACC2 is also a potent inhibitor of mitochondrial pyruvate transport, which interferes with pyruvate import into mitochondria and ultimately prevents extracellular lactate uptake as efficiently as a MCT1 inhibitor.
References:
1. Draoui N, Schicke O, Fernandes A, et al. Synthesis and pharmacological evaluation of carboxycoumarins as a new antitumor treatment targeting lactate transport in cancer cells. Bioorganic & Medicinal Chemistry, 2013, 21(22): 7107-7117.
2. Corbet C, Bastien E, Draoui N, et al. Interruption of lactate uptake by inhibiting mitochondrial pyruvate transport unravels direct antitumor and radiosensitizing effects. Nature Communications, 2018, 9(1): 1208.
| Storage | Store at -20°C |
| M.Wt | 309.32 |
| Cas No. | 1472624-85-3 |
| Formula | C18H15NO4 |
| Solubility | insoluble in EtOH; insoluble in H2O; ≥47.5 mg/mL in DMSO |
| Chemical Name | 7-(benzyl(methyl)amino)-2-oxo-2H-chromene-3-carboxylic acid |
| SDF | Download SDF |
| Canonical SMILES | OC(C(C(O1)=O)=CC2=C1C=C(N(C)CC3=CC=CC=C3)C=C2)=O |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Cell experiment:[1] | |
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Cell lines |
SiHa cells |
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Reaction Conditions |
72 h incubation |
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Applications |
7ACC2 inhibited SiHa cells proliferation by reducing lactate uptake (an MCT1-dependent process), with an EC50 value of 0.22 μM. |
| Animal experiment:[1,2] | |
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Animal models |
A SiHa mouse xenograft model |
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Dosage form |
3 mg/kg Intraperitoneal administration |
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Applications |
A single dose of 7ACC2 (3 mg/kg) to mice led to a Cmax of 1246 ng/ml (4 μM) in a very short time (Tmax = 10 min) associated with a plasma half-life of 4.5 h. 7ACC2 (3 mg/kg, q.d., for 5 and 10 days), when combined with radiotherapy, significantly delayed tumor growth in a SiHa mouse xenograft model. |
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Note |
The technical data provided above is for reference only. |
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References: 1. Draoui N, Schicke O, Fernandes A, et al. Synthesis and pharmacological evaluation of carboxycoumarins as a new antitumor treatment targeting lactate transport in cancer cells. Bioorganic & Medicinal Chemistry, 2013, 21(22): 7107-7117. 2. Corbet C, Bastien E, Draoui N, et al. Interruption of lactate uptake by inhibiting mitochondrial pyruvate transport unravels direct antitumor and radiosensitizing effects. Nature Communications, 2018, 9(1): 1208. |
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Quality Control & MSDS
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