Mito-LND (Mito-Lonidamine) is an orally bioactive inhibitor of oxidative phosphorylation (OXPHOS) that targets mitochondria. Mito-LND inhibits mitochondrial bioenergetics, stimulates the formation of reactive oxygen species, and induces autophagic cell death in lung cancer cells.

Physicochemical Properties

Molecular Formula	C43H45BRCL2N3OP
Molecular Weight	801.6207
Exact Mass	799.186
CAS #	2361564-49-8
PubChem CID	155977659
Appearance	Off-white to light yellow solid powder
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	3
Rotatable Bond Count	17
Heavy Atom Count	51
Complexity	938
Defined Atom Stereocenter Count	0
SMILES	[Br-].ClC1C([H])=C(C([H])=C([H])C=1C([H])([H])N1C2=C([H])C([H])=C([H])C([H])=C2C(C(N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[P+](C2C([H])=C([H])C([H])=C([H])C=2[H])(C2C([H])=C([H])C([H])=C([H])C=2[H])C2C([H])=C([H])C([H])=C([H])C=2[H])=O)=N1)Cl
InChi Key	XRSSFQSESARZNG-UHFFFAOYSA-N
InChi Code	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
Chemical Name	10-[[1-[(2,4-dichlorophenyl)methyl]indazole-3-carbonyl]amino]decyl-triphenylphosphanium;bromide
HS Tariff Code	2934.99.9001
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, avoid exposure to moisture.
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

ln Vitro	Mito-LND inhibits the invasion, migration, and development of lung cancer. H2030BrM3 and A549 cells' proliferation is inhibited by mito-LND, with IC50 values of 0.74 µM and 0.69 µM, respectively[1]. In H2030BrM3 cells, mito-LND suppresses the activities of mitochondrial complex I and II with IC50 values of 1.2 µM and 2.4 µM, respectively[1]. ROS production in H2030BrM3 lung cancer cells is increased by mito-LND (1 µM). In H2030BrM3 lung cancer cells, Mito-LND potently promotes mitochondrial ROS generation[1]. Mito-LND (2 µM) lowers phosphorylated AKT levels. In both the parent and metastatic lung cancer cell lines, Mito-LND also reduces the phosphorylation of P70S6K and other energy-sensing proteins, suggesting that Mito-LND directly inhibits mTOR signaling[1].
ln Vivo	Treatment with mito-LND (7.5 µmol/kg; oral gavage; 5 days per week; for 3 consecutive weeks) significantly increased potency against the progression and metastasis of lung cancer[1]. Additionally, A549 tumor xenografts develop less quickly when treated with mito-LND [1]. When NOD/SCID mice containing H2030BrM3 cells get mito-LND therapy, lung cancer brain metastases significantly decrease[1].
Animal Protocol	Animal/Disease Models: Athymic nude mice (5 weeks) injected with H2030BrM3 cells[1] Doses: 7.5 µmol/kg Route of Administration: po (oral gavage); 5 days per week; for 3 consecutive weeks Experimental Results: Dramatically diminished tumor progression.
References	[1]. Targeting lonidamine to mitochondria mitigates lung tumorigenesis and brain metastasis. Nat Commun. 2019 May 17;10(1):2205.

Solubility Data

Solubility (In Vitro)

DMSO : 50 mg/mL (62.37 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (3.12 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 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 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	1.2475 mL	6.2374 mL	12.4747 mL
	5 mM	0.2495 mL	1.2475 mL	2.4949 mL
	10 mM	0.1247 mL	0.6237 mL	1.2475 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.