ATP Synthesis-IN-4 

ATP Synthesis-IN-4 is a mitochondria-targeted small-molecule ligand that inhibits ATP synthesis. ATP Synthesis-IN-4 binds to mtDNA G4s in melanoma cells, thereby inducing changes in mitochondrial metabolism and inhibiting cell proliferation. ATP Synthesis-IN-4 suppresses the translation of key mitochondrial respiratory chain proteins (CYTB, ATP8, COX1, COX3, ND2) in melanoma cells, downregulates the expression of OXPHOS complexes, activates the phosphorylation of AMPK, and induces metabolic reprogramming to upregulate glycolysis. ATP Synthesis-IN-4 is applicable to relevant research on melanoma^[1].

ATP Synthesis-IN-4 (48 h) potently inhibits proliferation of malignant melanoma cell lines A375, SK-MEL-2, and A2058 with IC₅₀ values of 7.0 ± 0.41 μM, 8.0 ± 2.0 μM, and 16.8 ± 0.7 μM respectively, and shows low toxicity to noncancerous BJ skin fibroblasts (IC₅₀ >50 μM)^[1].
ATP Synthesis-IN-4 (1 μM; 20 min) is selectively localized to the mitochondria of live A375 cells, with no significant localization to the nucleus, lysosomes, or endoplasmic reticulum^[1].
ATP Synthesis-IN-4 (3.5-7 μM; 60 min) disrupts mitochondrial membrane potential in A375 cells in vitro in a concentration-dependent manner^[1].
ATP Synthesis-IN-4 (1 μM; 20 min) delivery to mitochondria in A375 cells is primarily dependent on mitochondrial membrane potential, as FCCP-induced MMP reduction inhibits its uptake, while CsA-mediated mPTP blockade does not^[1].
ATP Synthesis-IN-4 (5 μM; 1 min shaking, RT incubation) selectively binds to mtDNA G4 structures in vitro with high affinity (K_d 0.65−1.28 μM for top targets), showing far weaker binding to non-G4 DNA substrates^[1].
ATP Synthesis-IN-4 (3.5-7 μM; 48 h) downregulates expression of mitochondrial respiratory chain-related genes in A375 cells in a concentration-dependent manner (7 μM treatment reduces mRNA levels by ≥75% after 48 h) without affecting nuclear G4-associated genes KRAS and VEGF^[1].
ATP Synthesis-IN-4 (3.5-7 μM; 48 h) inhibits translation of key mitochondrial respiratory chain proteins (CYTB, ATP8, COX1, COX3, ND2) and downregulates OXPHOS complex expression in A375 cells, while activating AMPK phosphorylation^[1].
ATP Synthesis-IN-4 (3.5-7 μM; 2 h) impairs mitochondrial oxidative phosphorylation in A375 cells, reducing ATP production by ~83% (3.5 μM) and ~98% (7 μM) after 2 h treatment, while upregulating glycolysis in a concentration-dependent manner^[1].
ATP Synthesis-IN-4 (3.5-7 μM; 48 h) arrests A375 melanoma cells in the S phase of the cell cycle^[1].
ATP Synthesis-IN-4 (1.75 μM; 48 h) shows synergistic antiproliferative activity with 0.2 μM Vemurafenib against A375 cells (CI=0.67), reducing the IC₅₀ of ATP Synthesis-IN-4 to 0.63 ± 0.2 μM after 48 h treatment^[1].
ATP Synthesis-IN-4 (1.75 μM; 72 h), when combined with 0.2 μM Vemurafenib for 72 h, induces acute cellular senescence in A375 melanoma cells, as indicated by strong SA-β-galactosidase activity and enlarged cell morphology^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

419.38

C₂₀H₂₃BrN₂OS

OCCC[N+]1=C(/C=C/C2=CC=C(N(C)C)C=C2)SC3=CC=CC=C31.[Br-]

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Chan KH, et al. A New Combination Therapy Utilizing Mitochondria-Targeting Small-Molecule Ligands and Clinical Inhibitors against Melanoma. ACS Chem Biol. 2026;21(2):235-252.  [Content Brief]