Mito-LND

• CAT Number: I044536
• CAS Number: 2361564-49-8
• Molecular Formula: C43H45BrCl2N3OP
• Molecular Weight: 801.62
• Purity: ≥95%
• Synonyms: 10-[[1-[(2,4-dichlorophenyl)methyl]indazole-3-carbonyl]amino]decyl-triphenylphosphanium;bromide
• InChI: InChI=1S/C43H44Cl2N3OP.BrH/c44-35-29-28-34(40(45)32-35)33-48-41-27-17-16-26-39(41)42(47-48)43(49)46-30-18-5-3-1-2-4-6-19-31-50(36-20-10-7-11-21-36,37-22-12-8-13-23-37)38-24-14-9-15-25-38;/h7-17,20-29,32H,1-6,18-19,30-31,33H2;1H
• InChIKey: XRSSFQSESARZNG-UHFFFAOYSA-N
• SMILES: C1=CC=C(C=C1)[P+](CCCCCCCCCCNC(=O)C2=NN(C3=CC=CC=C32)CC4=C(C=C(C=C4)Cl)Cl)(C5=CC=CC=C5)C6=CC=CC=C6.[Br-]

Mito-LND (Mito-Lonidamine) is an orally active and mitochondria-targeted inhibitor of oxidative phosphorylation (OXPHOS). Mito-LND inhibits mitochondrial bioenergetics, stimulates the formation of reactive oxygen species, and induces autophagic cell death in lung cancer cells[1].
Mito-LND blocks lung cancer growth, migration, and invasion. Mito-LND inhibits cell growth of H2030BrM3 and A549 cells with IC50 values of 0.74 µM and 0.69 µM, respectively[1].
Mito-LND inhibits mitochondrial complex I and II activities with IC50 values of 1.2 µM and 2.4 µM, respectively in H2030BrM3 cells[1].
Mito-LND (1 µM) increases ROS generation in H2030BrM3 lung cancer cells. Mito-LND potently induces mitochondrial ROS generation in H2030BrM3 lung cancer cells[1].
Mito-LND (2 µM) decreases the levels of phosphorylated AKT. Mito-LND also decreases the phosphorylation of P70S6K and other energy-sensing proteins in both the parental and metastatic lung cancer cell lines, indicating that Mito-LND specifically downregulates mTOR signaling[1].
Mito-LND (7.5 µmol/kg; oral gavage; 5 days per week; for 3 consecutive weeks) treatment markedly enhanced potency against both lung cancer progression and metastasis[1].
Mito-LND also decreases the rate of growth of A549 tumor xenografts[1].
Mito-LND treatment shows a marked decrease in lung cancer brain metastasis in NOD/SCID mice bearing H2030BrM3 cells[1].

Reference

[1]. Gang Cheng, et al. Targeting lonidamine to mitochondria mitigates lung tumorigenesis and brain metastasis. Nat Commun. 2019 May 17;10(1):2205.
 [Content Brief]