Date published: 2026-7-4

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Asparagine synthetase Inhibitors

Asparagine synthetase inhibitors comprise a diverse array of compounds targeting the enzyme Asparagine synthetase (AS), a key player in cellular nitrogen metabolism. These inhibitors can be classified into direct and indirect categories based on their mechanisms of action. Direct inhibitors, including L-Asparagine, Acivicin, 6-Diazo-5-oxo-L-norleucine, DON, Compound 2, and Azaserine, exert their effects by directly interacting with the active site of AS or mimicking the structure of its substrates. L-Asparagine competes with endogenous aspartate for the AS active site, inhibiting asparagine synthesis. Acivicin and 6-Diazo-5-oxo-L-norleucine irreversibly bind to the AS active site, disrupting its catalytic function. DON and Azaserine act as structural analogs of aspartate, competitively inhibiting AS and impeding the conversion of aspartate to asparagine. Compound 2 disrupts AS catalysis by binding to its active site, offering insights into interventions selectively targeting AS. Indirect inhibitors, including L-Aspartic acid, Methotrexate, Fludarabine, Glutamic-oxaloacetic transaminase inhibitor, Aminooxyacetic acid (AOA), and L-Asparaginase, modulate AS activity through pathways beyond direct enzyme interaction. L-Aspartic acid influences AS indirectly by altering substrate availability. Methotrexate interferes with AS through inhibition of dihydrofolate reductase, disrupting folate metabolism essential for asparagine synthesis. Fludarabine, a purine analog, impacts AS indirectly by disrupting purine metabolism. The Glutamic-oxaloacetic transaminase inhibitor targets transaminases involved in generating aspartate, indirectly affecting AS. AOA inhibits transaminases, indirectly influencing aspartate availability for AS. L-Asparaginase, while directly hydrolyzing extracellular asparagine, indirectly inhibits AS as cells increase asparagine synthesis to meet demand. Understanding the diverse mechanisms employed by AS inhibitors sheds light on the intricate regulation of cellular nitrogen metabolism. These compounds serve as valuable tools for probing the role of AS in cellular processes, offering insights where dysregulated nitrogen metabolism plays a crucial role.

SEE ALSO...

Product NameCAS #Catalog #QUANTITYPriceCitationsRATING

Acivicin

42228-92-2sc-200498B
sc-200498C
sc-200498
sc-200498D
1 mg
5 mg
10 mg
25 mg
$104.00
$416.00
$655.00
$1301.00
10
(2)

Acivicin is a direct inhibitor of Asparagine synthetase, irreversibly binding to the AS active site and disrupting its catalytic function. By forming a covalent bond with AS, Acivicin inhibits the enzyme's ability to convert aspartate to asparagine, thereby affecting cellular nitrogen metabolism. Acivicin's mechanism highlights the direct intervention possible in modulating AS activity.

6-Diazo-5-oxo-L-norleucine

157-03-9sc-227078
sc-227078A
sc-227078B
sc-227078C
5 mg
25 mg
100 mg
250 mg
$88.00
$291.00
$926.00
$2195.00
(0)

6-Diazo-5-oxo-L-norleucine is a direct inhibitor of Asparagine synthetase, irreversibly binding to the AS active site and inhibiting its catalytic function. By disrupting the conversion of aspartate to asparagine, 6-Diazo-5-oxo-L-norleucine provides a specific means to investigate the role of asparagine in cellular processes regulated by AS.

Azaserine

115-02-6sc-29063
sc-29063A
50 mg
250 mg
$312.00
$924.00
15
(3)

Azaserine is a direct inhibitor of Asparagine synthetase, competitively inhibiting the enzyme's catalytic activity. By mimicking the structure of aspartate, Azaserine interferes with the conversion of aspartate to asparagine, leading to reduced cellular asparagine levels. Azaserine's specificity for AS makes it a valuable tool for investigating the consequences of selective asparagine depletion on cellular processes.

L-Aspartic acid

56-84-8sc-472377A
sc-472377
sc-472377B
25 g
100 g
500 g
$40.00
$33.00
$48.00
(0)

L-Aspartic acid is an indirect inhibitor of Asparagine synthetase, influencing AS activity by altering substrate availability. By providing a precursor to asparagine synthesis, L-Aspartic acid indirectly modulates AS, impacting the enzyme's ability to convert aspartate to asparagine. L-Aspartic acid's indirect mechanism sheds light on the multifaceted regulation of AS in cellular nitrogen metabolism.

Methotrexate

59-05-2sc-3507
sc-3507A
100 mg
500 mg
$94.00
$213.00
33
(5)

Methotrexate is an indirect inhibitor of Asparagine synthetase, interfering with AS through the inhibition of dihydrofolate reductase. This disruption affects folate metabolism essential for asparagine synthesis. Methotrexate's indirect modulation of AS activity provides insights into the interconnected nature of cellular metabolic pathways influencing asparagine production.

Fludarabine

21679-14-1sc-204755
sc-204755A
5 mg
25 mg
$58.00
$204.00
15
(1)

Fludarabine is an indirect inhibitor of Asparagine synthetase, impacting AS activity by disrupting purine metabolism. By acting as a purine analog, Fludarabine indirectly influences AS, providing a unique avenue to explore the consequences of altered purine metabolism on asparagine synthesis. Fludarabine's mechanism highlights the intricate connections between cellular pathways regulating AS activity.