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Protein / target

Succinate-semialdehyde dehydrogenase, mitochondrial

Encoded byALDH5A1P51649Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
3
Approved medicines
Open Targets target-level
View by indication →
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

Succinate-semialdehyde dehydrogenase (NAD+)

Strongest disease association

Succinic semialdehyde dehydrogenase deficiency

Via encoding gene ALDH5A1 · Genetic evidence · score 0.92

Therapeutic position

Established drug target

Small molecules

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function overview

Catalyzes one step in the degradation of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA)

Subcellular location

Mitochondrion
Domains and Gene Ontology detail (8)

Gene Ontology

  • Cmitochondrial matrix
  • Cmitochondrion
  • Fidentical protein binding
  • Fsuccinate-semialdehyde dehydrogenase (NAD+) activity
  • Pcentral nervous system development
  • Pgamma-aminobutyric acid catabolic process
  • Pglutamate metabolic process
  • Psuccinate metabolic process

535 aa · 57 kDa · 2 isoforms

Biological roles

Reactome v97

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Metabolic enzyme activityGO
View supporting evidence

Metabolic enzyme activity

  • ·succinate-semialdehyde dehydrogenase (NAD+) activity
  • ·glutamate metabolic process
  • ·succinate metabolic process
View underlying pathways (1)

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Interaction neighbourhood

STRING v12.0

Proteins with the strongest functional or physical association. Node size and line weight reflect STRING confidence; hover or select a partner to inspect one association.

ABATCSOGDHMDH2ACLYIDH2IDH1PCOGDHLIDH3AALDH5A1

10 strongest partners — larger node and heavier line mean higher confidence

Functional and physical associations from STRING v12.0. Only associations with this protein are drawn — partner-to-partner links are not part of this evidence.

Approved medicines with mapped indications

1 medicine · 5 areas

Approved therapies targeting this protein, grouped by what they are approved to treat — the disease-first view of the medicines below. Relationships come from the canonical approved-indication graph (ChEMBL phase-4), the same source as the drug cards.

Bipolar Disorder1 medicine
Epilepsy1 medicine
Epilepsy, Absence1 medicine
Mitochondrial Diseases1 medicine
Seizures1 medicine

3 medicines meet Open Targets' target-level approved-medicine definition; the 1 shown here are those on this page with a canonical approved disease indication in the graph. Approved indications from ChEMBL (phase-4), via the canonical drug→disease graph.

Drugs targeting this protein

1

How approved and investigational drugs engage this protein — mechanism and action type, direct vs complex targeting, and how broadly each acts across other targets. A drug-first view (the section above groups the approved ones disease-first); direct binders with few recorded targets are listed first.

Valproic Acid
Narrow target profileApprovedInhibitor

Succinate semialdehyde dehydrogenase inhibitor

Indicated for Bipolar Disorder, Epilepsy, Epilepsy, Absence, Mitochondrial Diseases

Direct interaction with this protein · Only this protein recorded as a target

ChEMBL mechanism, action type, target identity and approved indications. Open Targets clinical status.

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene ALDH5A1

Gene-level evidence surfaced through the gene ALDH5A1 that encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

Succinic semialdehyde dehydrogenase deficiency
0.94Well supported

Genetic evidence dominant · Open Targets 0.84

Genetic Diseases, Inborn
0.86Well supported

Genetic evidence dominant · Open Targets 0.52

Epilepsy
0.75Well supported

Clinical evidence dominant · Open Targets 0.61

Bipolar Disorder
0.75Moderately supported

Clinical evidence dominant · Open Targets 0.61

Major depressive disorder
0.70Moderately supported

Clinical evidence dominant · Open Targets 0.57

View evidence synthesis (5)
Succinic semialdehyde dehydrogenase deficiencyWell supported
0.94
agreement 0.821.00
Genetic83%Animal model13%Literature4%Genetic literaturedup

Open Targets aggregate 0.84 · 3 independent evidence families · 1 not counted as duplicate

Genetic Diseases, InbornWell supported
0.86
agreement 0.721.00
Genetic98%Literature2%

Open Targets aggregate 0.52 · 2 independent evidence families

EpilepsyWell supported
0.75
agreement 0.600.91
Clinical98%Literature2%

Open Targets aggregate 0.61 · 2 independent evidence families

Bipolar DisorderModerately supported
0.75
agreement 0.590.90
Clinical99%Literature2%

Open Targets aggregate 0.61 · 2 independent evidence families

Major depressive disorderModerately supported
0.70
agreement 0.550.86
Clinical100%Literature0%

Open Targets aggregate 0.57 · 2 independent evidence families

The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the per-type scores above show the calculation.

Show all associations
Succinic semialdehyde dehydrogenase deficiency0.84
Epilepsy0.61
Bipolar Disorder0.61
Major depressive disorder0.57
Genetic Diseases, Inborn0.52

Drug development

3 compounds recorded · 3 approved

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines. Distinct from the 1 drug that targets this protein in Forefront's canonical graph (1 with a mapped approved indication, shown above): these count different sets and are not a subset relation.

View all recorded compounds (3)
VALPROIC ACIDApproval
DIVALPROEX SODIUMApproval
VALPROATE SODIUMApproval

Open Targets known-drugs universe. Drug name and highest clinical stage only — the disease relationship is NOT read from this slice (it carries trial-context noise); approved indications come from the canonical graph above.

Tractability

Small moleculesStrong

Approved Drug and Structure with Ligand support this modality.

Protein degradersEmerging

Feasibility evidence (database ubiquitination and half-life data) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (7)
SM · Approved DrugSM · Structure with LigandSM · High-Quality PocketSM · Druggable FamilyPR · Database UbiquitinationPR · Half-life DataPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

Clinical trials

30

Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein. Ranked by active status, then clinical phase and recency, and spread across the targeting drugs.

View all trials (26)

UNKNOWN · via Valproic Acid · NCT06485726

COMPLETED · via Valproic Acid · NCT03914534

TERMINATED · via Valproic Acid · NCT02343575

COMPLETED · via Valproic Acid · NCT00254488

TERMINATED · via Valproic Acid · NCT00203385

COMPLETED · via Valproic Acid · NCT01115959

COMPLETED · via Valproic Acid · NCT00048802

COMPLETED · via Valproic Acid · NCT06248931

TERMINATED · via Valproic Acid · NCT02374567

COMPLETED · via Valproic Acid · NCT01586208

COMPLETED · via Valproic Acid · NCT00681980

ClinicalTrials.gov via the drug-target graph.

What's happening now

12

Recent therapeutic activity around this target — regulatory actions, clinical trials and safety signals for a drug that targets this protein, plus publications where such a drug is a genuine subject. Every item is reached indirectly through the drug, not the protein itself; incidental mentions (a paper that merely measures a drug) and press items are excluded.

  1. Supplemental approval2026-06-25

    Supplemental approval: VALPROIC ACID (ANDA073229)

    fda · regulatory · fda · via Valproic Acid

  2. New publication2020-04-14
    A phase 2 study of valproic acid and radiation, followed by maintenance valproic acid and bevacizumab in children with newly diagnosed diffuse intrinsic pontine glioma or high-grade glioma.

    Pediatric blood & cancer · 2020 · 50 citations · Europe PMC · via Valproic Acid

  3. New publication2018-03-14
    Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder.

    Bipolar disorders · 2018 · 1,126 citations · Europe PMC · via Valproic Acid

  4. Label change2015-12-26

    Label change: VALPROIC ACID (ANDA073229)

    fda · regulatory · fda · via Valproic Acid

  5. Label change2015-12-26

    Label change: VALPROIC ACID (ANDA073229)

    fda · regulatory · fda · via Valproic Acid

  6. Label change2014-08-05

    Label change: VALPROIC ACID (ANDA073229)

    fda · regulatory · fda · via Valproic Acid

  7. Supplemental approval2001-06-29

    Supplemental approval: VALPROIC ACID (ANDA073229)

    fda · regulatory · fda · via Valproic Acid

  8. Supplemental approval2000-01-27

    Supplemental approval: VALPROIC ACID (ANDA073229)

    fda · regulatory · fda · via Valproic Acid

  9. Supplemental approval1998-10-14

    Supplemental approval: VALPROIC ACID (ANDA073229)

    fda · regulatory · fda · via Valproic Acid

  10. Supplemental approval1996-11-15

    Supplemental approval: VALPROIC ACID (ANDA073229)

    fda · regulatory · fda · via Valproic Acid

  11. Supplemental approval1993-01-15

    Supplemental approval: VALPROIC ACID (ANDA073229)

    fda · regulatory · fda · via Valproic Acid

  12. Regulatory approval1991-10-29

    Approval: VALPROIC ACID (ANDA073229)

    fda · regulatory · fda · via Valproic Acid

Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.