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Protein / target

Proteasome subunit alpha-type 8

Encoded byPSMA8Q8TAA3Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
5
Approved medicines
Open Targets target-level
View by indication →
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

Proteasomal protein catabolic process

Strongest disease association

Neoplasms

Via encoding gene PSMA8 · Clinical evidence · score 0.47

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

Component of the spermatoproteasome, a proteasome specifically found in testis that promotes acetylation-dependent degradation of histones, thereby participating actively to the exchange of histones during spermatogenesis.

View complete UniProt function annotation

Component of the spermatoproteasome, a proteasome specifically found in testis that promotes acetylation-dependent degradation of histones, thereby participating actively to the exchange of histones during spermatogenesis. The proteasome is a protein complex that degrades unneeded or damaged proteins by proteolysis, a chemical reaction that breaks peptide bonds. Required for 20S core proteasome assembly, essential for the degradation of meiotic proteins RAD51 and RPA1 at late prophase I and the progression of meiosis I during spermatogenesis. Localizes to the synaptonemal complex, a 'zipper'-like structure that holds homologous chromosome pairs in synapsis during meiotic prophase I

Subcellular location

Nucleus
Domains and Gene Ontology detail (12)

Gene Ontology

  • Ccytosol
  • Cextracellular exosome
  • Cnucleus
  • Cproteasome core complex, alpha-subunit complex
  • Cspermatoproteasome complex
  • Pcell differentiation
  • Pflagellated sperm motility
  • Pmeiotic cell cycle
  • Pproteasomal protein catabolic process
  • Pproteasome-mediated ubiquitin-dependent protein catabolic process
  • Pregulation of meiosis I
  • Pspermatogenesis

256 aa · 29 kDa · 3 isoforms

Approved medicines with mapped indications

3 medicines · 2 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.

Multiple Myeloma1 medicine
Neoplasms3 medicines

5 medicines meet Open Targets' target-level approved-medicine definition; the 3 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

4

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.

bortezomib
ApprovedInhibitor

26S proteasome inhibitor

Indicated for Neoplasms

Acts on a complex — shared with PSMD1, PSMB2, PSMB1 +34 more · 1 of 38 recorded protein targets — broad pharmacology

carfilzomib
ApprovedInhibitor

26S proteasome inhibitor

Indicated for Multiple Myeloma, Neoplasms

Acts on a complex — shared with PSMD1, PSMB2, PSMB1 +34 more · 1 of 38 recorded protein targets — broad pharmacology

ixazomib
ApprovedInhibitor

26S proteasome inhibitor

Indicated for Neoplasms

Acts on a complex — shared with PSMD1, PSMB2, PSMB1 +34 more · 1 of 38 recorded protein targets — broad pharmacology

Oprozomib
Phase 2Inhibitor

26S proteasome inhibitor

Acts on a complex — shared with PSMD1, PSMB2, PSMB1 +34 more · 1 of 38 recorded protein targets — broad pharmacology

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 PSMA8

Gene-level evidence surfaced through the gene PSMA8that 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.

Neoplasms
0.58Moderately supported

Clinical evidence dominant · Open Targets 0.47

Lymphoma, Large B-Cell, Diffuse
0.41Limited support

Clinical evidence dominant · Open Targets 0.33

View evidence synthesis (2)
NeoplasmsModerately supported
0.58
agreement 0.430.74
Clinical99%Literature1%

Open Targets aggregate 0.47 · 2 independent evidence families

Lymphoma, Large B-Cell, DiffuseLimited support
0.41
agreement 0.240.57
Clinical100%

Open Targets aggregate 0.33 · 1 independent evidence family

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
Neoplasms0.47
Lymphoma, Large B-Cell, Diffuse0.33

Drug development

7 compounds recorded · 5 approved · 2 in clinical development

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines. Distinct from the 4 drugs that target this protein in Forefront's canonical graph (3 with a mapped approved indication, shown above): these count different sets and are not a subset relation.

View all recorded compounds (7)
OPROZOMIBPhase 2
MARIZOMIBPhase 3
CARFILZOMIBApproval
IXAZOMIB CITRATEApproval
IXAZOMIBApproval
BORTEZOMIBApproval
BORTEZOMIB D-MANNITOLApproval

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 High-Quality Ligand support this modality.

Protein degradersEmerging

Feasibility evidence (database ubiquitination and small molecule binder) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (5)
SM · Approved DrugSM · High-Quality LigandSM · Druggable FamilyPR · Database UbiquitinationPR · 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)

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 2 drugs that target 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. Trial status changed2026-07-31

    A Phase 3b, Multicenter, Open-label, Daratumumab Long-term Extension Study

    Status changed to Active, not recruiting · ClinicalTrials.gov · via carfilzomib

  2. Trial status changed2026-07-30

    64407564MMY3009: A Phase 3 Randomized Study Comparing Talquetamab in Combination With Pomalidomide (Tal-P), Talquetamab in Combination With Teclistamab (Tal-Tec), and Investigator's Choice of Either Elotuzumab, Pomalidomide, and Dexamethasone (EPd) or Pom

    Status changed to Active, not recruiting · ClinicalTrials.gov · via bortezomib

  3. Regulatory approval2026-07-20

    Approval: CARFILZOMIB (ANDA209526)

    fda · regulatory · fda · via carfilzomib

  4. Withdrawn from market2025-08-07

    Market withdrawal: Bortezomib Hospira (EMA)

    ema · market · ema · via bortezomib

  5. Safety communication2019-11-21

    Drug Safety Update: Carfilzomib (Kyprolis▼): risk of reactivation of hepatitis B virus

    mhra · safety · mhra · via carfilzomib

  6. Safety communication2019-08-19

    Drug Safety Update: Carfilzomib (Kyprolis▼): reminder of risk of potentially fatal cardiac events

    mhra · safety · mhra · via carfilzomib

  7. Accelerated approval granted2015-11-19

    Accelerated approval: Kyprolis (EMA)

    ema · regulatory · ema · via carfilzomib

  8. Regulatory approval2015-07-20

    Approval: Bortezomib Accord (EMA)

    ema · regulatory · ema · via bortezomib

  9. New publication2011-08-01
    Proteasome inhibition in myelodysplastic syndromes and acute myelogenous leukemia cell lines.

    Cancer investigation · 2011 · 12 citations · Europe PMC · via bortezomib

  10. New publication2011-02-21
    Weekly bortezomib in combination with temsirolimus in relapsed or relapsed and refractory multiple myeloma: a multicentre, phase 1/2, open-label, dose-escalation study.

    The Lancet. Oncology · 2011 · 66 citations · Europe PMC · via bortezomib

  11. New publication2010-12-14
    Phase 2 trial of rituximab and bortezomib in patients with relapsed or refractory mantle cell and follicular lymphoma.

    Cancer · 2011 · 31 citations · Europe PMC · via bortezomib

  12. New publication2010-02-08
    Phase II trial of weekly bortezomib in combination with rituximab in relapsed or relapsed and refractory Waldenstrom macroglobulinemia.

    Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2010 · 112 citations · Europe PMC · via bortezomib

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.