Date published: 2025-11-4

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Cytochrome c oxidase (COX) Inhibitors

Cytochrome c oxidase (COX), also known as Complex IV of the mitochondrial electron transport chain (ETC), plays a pivotal role in cellular energy production. It catalyzes the reduction of oxygen to water, a process that is crucial for the efficient production of ATP through oxidative phosphorylation. COX functions as the final electron acceptor in the ETC, receiving electrons from cytochrome c and transferring them to molecular oxygen. This process creates a proton gradient across the mitochondrial membrane, which is essential for ATP synthesis by ATP synthase (Complex V). Dysregulation or malfunction of COX can significantly impact cellular metabolism and energy homeostasis, highlighting its critical role in bioenergetic processes.

Targeting the mitochondrial electron transport chain (ETC) for disruption or inhibition is a strategy that can profoundly affect cellular energy production. Inhibitors of the ETC components, such as Complexes I, III, IV, and ATP synthase, are used to understand the intricacies of mitochondrial function and the regulation of cellular metabolism. By blocking specific steps in the electron transport process, these inhibitors can help elucidate the mechanisms of energy production and the role of mitochondria in various cellular processes. Inhibition of the ETC can lead to a reduction in ATP generation, alteration of mitochondrial membrane, and increased production of reactive oxygen species (ROS).

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Product NameCAS #Catalog #QUANTITYPriceCitationsRATING

Rotenone

83-79-4sc-203242
sc-203242A
1 g
5 g
$89.00
$254.00
41
(1)

Specifically inhibits Complex I (NADH:ubiquinone oxidoreductase) by binding to its ubiquinone binding site, thereby blocking electron transfer from NADH to ubiquinone.

Piericidin A

2738-64-9sc-202287
2 mg
$285.00
24
(1)

Another Complex I inhibitor, it is structurally similar to ubiquinone and competes with it for binding at the active site of Complex I.

Antimycin A

1397-94-0sc-202467
sc-202467A
sc-202467B
sc-202467C
5 mg
10 mg
1 g
3 g
$54.00
$62.00
$1642.00
$4600.00
51
(1)

Targets Complex III (cytochrome bc1 complex), binding to the Qo site and inhibiting electron transfer from ubiquinol to cytochrome c.

Oligomycin

1404-19-9sc-203342
sc-203342C
10 mg
1 g
$146.00
$12250.00
18
(2)

Inhibits ATP synthase (Complex V), binding to the Fo subunit and preventing proton flow through the enzyme, thereby inhibiting ATP synthesis.

Myxothiazol

76706-55-3sc-507550
1 mg
$145.00
(0)

Both inhibit Complex III, but through different mechanisms. Myxothiazol binds to the Qi site, while stigmatellin binds at the interface of the cytochrome b and the Rieske iron-sulfur protein.

Bongkrekic acid

11076-19-0sc-205606
100 µg
$418.00
10
(1)

These inhibit the adenine nucleotide translocator (ANT), indirectly affecting the ETC by disrupting the transport of ADP and ATP across the mitochondrial membrane.

2-Thenoyltrifluoroacetone

326-91-0sc-251801
5 g
$36.00
1
(1)

A specific inhibitor of Complex II (succinate dehydrogenase), it binds to the succinate binding site and prevents electron transfer to ubiquinone.

Carboxine

5234-68-4sc-234286
250 mg
$21.00
1
(1)

Also an inhibitor of Complex II, similar in action to TTFA.

2,4-Dinitrophenol, wetted

51-28-5sc-238345
250 mg
$58.00
2
(1)

While not a direct inhibitor, DNP uncouples oxidative phosphorylation by carrying protons across the mitochondrial membrane, reducing the proton gradient necessary for ATP synthesis.