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Protein / target

DNA polymerase alpha catalytic subunit

Encoded byPOLA1P09884Homo 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

DNA-directed DNA polymerase

Strongest disease association

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Via encoding gene POLA1 · Clinical evidence · score 0.60

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

Catalytic subunit of the DNA polymerase alpha complex (also known as the alpha DNA polymerase-primase complex) which plays an essential role in the initiation of DNA synthesis.

View complete UniProt function annotation

Catalytic subunit of the DNA polymerase alpha complex (also known as the alpha DNA polymerase-primase complex) which plays an essential role in the initiation of DNA synthesis. During the S phase of the cell cycle, the DNA polymerase alpha complex (composed of a catalytic subunit POLA1, a regulatory subunit POLA2 and two primase subunits PRIM1 and PRIM2) is recruited to DNA at the replicative forks via direct interactions with MCM10 and WDHD1. The primase subunit of the polymerase alpha complex initiates DNA synthesis by oligomerising short RNA primers on both leading and lagging strands. These primers are initially extended by the polymerase alpha catalytic subunit and subsequently transferred to polymerase delta and polymerase epsilon for processive synthesis on the lagging and leading strand, respectively. The reason this transfer occurs is because the polymerase alpha has limited processivity and lacks intrinsic 3' exonuclease activity for proofreading error, and therefore is not well suited for replicating long complexes. In the cytosol, responsible for a substantial proportion of the physiological concentration of cytosolic RNA:DNA hybrids, which are necessary to prevent spontaneous activation of type I interferon responses (PubMed:27019227)

Subcellular location

NucleusCytoplasm, cytosol
Domains and Gene Ontology detail (27)

Gene Ontology

  • Calpha DNA polymerase:primase complex
  • Cchromatin
  • Ccytosol
  • Cnuclear envelope
  • Cnuclear matrix
  • Cnucleolus
  • Cnucleoplasm
  • Cnucleus
  • Fchromatin binding
  • FDNA binding
  • FDNA replication origin binding
  • FDNA-directed DNA polymerase activity

1462 aa · 166 kDa

Approved medicines with mapped indications

2 medicines · 6 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.

Precursor Cell Lymphoblastic Leukemia-Lymphoma2 medicines
Leukemia, Lymphoid1 medicine
Leukemia, Myeloid, Acute1 medicine
Meningeal Carcinomatosis1 medicine
Meningeal Neoplasms1 medicine
Broader indication categories (1)
Neoplasms2 medicines

Broad umbrella indications (e.g. “Neoplasms”). Shown here because every medicine also appears under a more specific disease above — kept for completeness, de-emphasised for clarity.

5 medicines meet Open Targets' target-level approved-medicine definition; the 2 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

2

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.

clofarabine
ApprovedInhibitor

DNA polymerase (alpha/delta/epsilon) inhibitor

Indicated for Precursor Cell Lymphoblastic Leukemia-Lymphoma, Neoplasms

Acts on a complex — shared with POLD4, POLD3, POLD1 +7 more · 1 of 14 recorded protein targets — broad pharmacology

cytarabine
ApprovedInhibitor

DNA polymerase (alpha/delta/epsilon) inhibitor

Indicated for Leukemia, Lymphoid, Leukemia, Myeloid, Acute, Meningeal Carcinomatosis, Meningeal Neoplasms

Acts on a complex — shared with POLD4, POLD3, POLD1 +7 more · 1 of 11 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 POLA1

Gene-level evidence surfaced through the gene POLA1that 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.

Precursor Cell Lymphoblastic Leukemia-Lymphoma
0.74Moderately supported

Clinical evidence dominant · Open Targets 0.60

Carcinoma, Non-Small-Cell Lung
0.73Moderately supported

Clinical evidence dominant · Open Targets 0.59

Leukemia, Lymphocytic, Chronic, B-Cell
0.73Moderately supported

Clinical evidence dominant · Open Targets 0.59

Leukemia, Myeloid, Acute
0.73Moderately supported

Clinical evidence dominant · Open Targets 0.59

Ovarian carcinoma
0.70Moderately supported

Clinical evidence dominant · Open Targets 0.57

View evidence synthesis (5)
Precursor Cell Lymphoblastic Leukemia-LymphomaModerately supported
0.74
agreement 0.580.89
Clinical99%Literature1%

Open Targets aggregate 0.60 · 2 independent evidence families

Carcinoma, Non-Small-Cell LungModerately supported
0.73
agreement 0.580.89
Clinical99%Literature1%

Open Targets aggregate 0.59 · 2 independent evidence families

Leukemia, Lymphocytic, Chronic, B-CellModerately supported
0.73
agreement 0.570.88
Clinical99%Literature1%

Open Targets aggregate 0.59 · 2 independent evidence families

Leukemia, Myeloid, AcuteModerately supported
0.73
agreement 0.560.89
Clinical100%

Open Targets aggregate 0.59 · 1 independent evidence family

Ovarian carcinomaModerately supported
0.70
agreement 0.550.86
Clinical97%Literature3%

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
Precursor Cell Lymphoblastic Leukemia-Lymphoma0.60
Carcinoma, Non-Small-Cell Lung0.59
Leukemia, Lymphocytic, Chronic, B-Cell0.59
Leukemia, Myeloid, Acute0.59
Ovarian carcinoma0.57
Neoplasms0.55

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 2 drugs that target this protein in Forefront's canonical graph (2 with a mapped approved indication, shown above): these count different sets and are not a subset relation.

View all recorded compounds (7)
FLUDARABINE PHOSPHATEApproval
CLOFARABINEApproval
GEMCITABINEApproval
GEMCITABINE HYDROCHLORIDEApproval
TROXACITABINEPhase 2
CYTARABINEApproval
ASPACYTARABINEPhase 2

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 small molecule binder) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (6)
SM · Approved DrugSM · Structure with LigandSM · 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)

ACTIVE_NOT_RECRUITING · via cytarabine · NCT03020030

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. Label change2026-08-03

    Label change: CYTARABINE (ANDA072168)

    fda · regulatory · fda · via cytarabine

  2. Label change2026-08-03

    Label change: CYTARABINE (ANDA072945)

    fda · regulatory · fda · via cytarabine

  3. Label change2026-08-03

    Label change: CYTARABINE (ANDA075383)

    fda · regulatory · fda · via cytarabine

  4. Label change2026-07-29

    Label change: CYTARABINE (ANDA071868)

    fda · regulatory · fda · via cytarabine

  5. Withdrawn from market2023-10-18

    Market withdrawal: Ivozall (EMA)

    ema · market · ema · via clofarabine

  6. New publication2013-02-10
    Safety and pharmacokinetics of the antisense oligonucleotide (ASO) LY2181308 as a single-agent or in combination with idarubicin and cytarabine in patients with refractory or relapsed acute myeloid leukemia (AML).

    Investigational new drugs · 2013 · 42 citations · Europe PMC · via cytarabine

  7. New publication2012-05-14
    Clofarabine plus cytarabine compared with cytarabine alone in older patients with relapsed or refractory acute myelogenous leukemia: results from the CLASSIC I Trial.

    Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2012 · 133 citations · Europe PMC · via cytarabine

  8. New publication2009-12-21
    Phase II study of clofarabine monotherapy in previously untreated older adults with acute myeloid leukemia and unfavorable prognostic factors.

    Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2010 · 151 citations · Europe PMC · via clofarabine

  9. New publication2009-03-01
    Phase II study of intermediate-dose cytarabine in patients with relapsed or refractory Ewing sarcoma: a report from the Children's Oncology Group.

    Pediatric blood & cancer · 2009 · 51 citations · Europe PMC · via cytarabine

  10. Regulatory approval1994-02-28

    Approval: CYTARABINE (ANDA072945)

    fda · regulatory · fda · via cytarabine

  11. Regulatory approval1990-08-31

    Approval: CYTARABINE (ANDA072168)

    fda · regulatory · fda · via cytarabine

  12. Regulatory approval1990-06-04

    Approval: CYTARABINE (ANDA071868)

    fda · regulatory · fda · via cytarabine

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.