Drug pipeline
Full profile accessExplore the programs pursuing this target and their development progress.
- Drug candidates
- Developers
- Development stage
Target intelligence / Profile preview
Argininosuccinate synthetase (ASS)
- Target
- ASS
- Molecular classification
- Enzyme, Ligase, Urea cycle enzyme
01
Overview
Argininosuccinate synthetase is a homotetrameric enzyme (EC 6.3.4.5) comprising 412 amino acids in humans and encoded by the ASS1 gene on chromosome 9. It catalyzes the ATP-dependent condensation of citrulline and aspartate to form argininosuccinate, which is a precursor for arginine biosynthesis and a key intermediate in the urea cycle for nitrogen excretion. The enzyme is prominently expressed in the liver and kidney and plays a crucial role in maintaining systemic arginine levels, detoxifying ammonia, and regulating nitric oxide production for vascular health. Genetic deficiency causes type I citrullinemia, while somatic downregulation in tumors confers a metabolic vulnerability exploited by targeted cancer therapies.
- Other names
- ASS1Argininosuccinate synthaseEC 6.3.4.5
02
Mechanism of action
Enzyme activation: SPA/LM-2I enhance ASS1 activity, inhibiting tumor proliferation. Arginine deprivation: Therapeutic depletion leads to selective death of ASS1-deficient tumor cells. Substrate supplementation: Supplementation with arginine or citrulline is used in metabolic deficiency.
03
Biological functions
Arginine biosynthesis (rate-limiting step)Urea cycle (removal of excess nitrogen)Creatine, polyamine, and nitric oxide synthesisRegulation of vascular physiology via citrulline-NO cycle
04
Disease associations
Urea cycle disorder (citrullinemia due to genetic deficiency)Cancer (down-regulation or silencing is common in various cancers: melanoma, breast, pancreatic, bladder, etc. Leading to arginine auxotrophy of tumor cells)Tumor suppressor (loss potentiates tumor growth and poor prognosis)Neurological disorders (due to hyperammonemia from citrullinemia)
05
Safety considerations
Hyperammonemia risk from enzyme deficiencyTumor resistance and escape to arginine-depleting therapiesSystemic side effects from arginine deprivation (potential impact on immune and vascular function)
06
Interacting drugs
Spinosyn A (SPA, activates ASS1 enzymatic activity)
3 more in the full profile.
07
Biomarkers
ASS1 expression levels (used to stratify cancer patients for arginine deprivation therapies)Plasma citrulline/ammonia (used to diagnose citrullinemia)Arginine/citrulline ratios (metabolic monitoring)
Beyond the preview
Go deeper on Argininosuccinate synthetase (ASS).
Explore the evidence, development activity, and competitive landscape with Gosset’s full data platform.
Clinical trials
Full profile accessFollow the clinical studies evaluating therapies directed at this target.
- Trial design
- Status
- Readouts
Competitive landscape
Full profile accessCompare approaches across drug candidates, modalities, and indications.
- Programs
- Modalities
- Indications
Literature & evidence
Full profile accessInvestigate the research and source evidence behind target biology and development.
- Publications
- Sources
- Analysis
Patents
Full profile accessExplore patent activity around therapies and technologies addressing this target.
- Patents
- Assignees
- Technologies
Research & analysis
Full profile accessConnect target biology, drug development, and emerging evidence in your research.
- Biology
- Development news
- Analysis
Bring the full picture into focus.
See how Gosset can support your research on Argininosuccinate synthetase (ASS).