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Protein / target

Ribonucleoside-diphosphate reductase large subunit

Encoded byRRM1P23921Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
7
Approved medicines
Open Targets target-level
View by indication →
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

Ribonucleoside-diphosphate reductase

Strongest disease association

Carcinoma, Non-Small-Cell Lung

Via encoding gene RRM1 · Clinical evidence · score 0.62

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

Provides the precursors necessary for DNA synthesis.

View complete UniProt function annotation

Provides the precursors necessary for DNA synthesis. Catalyzes the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides

Subcellular location

Cytoplasm
Domains and Gene Ontology detail (20)

Domains & features

ATP-cone

Gene Ontology

  • Ccytosol
  • Cmitochondrion
  • Cribonucleoside-diphosphate reductase complex
  • FATP binding
  • Fdisordered domain specific binding
  • Fidentical protein binding
  • Fribonucleoside-diphosphate reductase activity
  • Fribonucleoside-diphosphate reductase activity, glutaredoxin disulfide as acceptor
  • Fribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor
  • P2'-deoxyribonucleotide biosynthetic process
  • Pdeoxyribonucleotide biosynthetic process
  • PDNA repair

792 aa · 90 kDa

Biological roles

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

Cell-cycle regulationGO
View supporting evidence

Cell-cycle regulation

  • ·positive regulation of G1/S transition of mitotic cell cycle
  • ·positive regulation of G2/M transition of mitotic cell cycle

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

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.

Anemia, Sickle Cell1 medicine
Carcinoma, Squamous Cell1 medicine
Leukemia, Myelogenous, Chronic, BCR-ABL Positive1 medicine
Melanoma1 medicine
Precursor Cell Lymphoblastic Leukemia-Lymphoma1 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.

7 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

Ribonucleoside-diphosphate reductase RR1 inhibitor

Indicated for Precursor Cell Lymphoblastic Leukemia-Lymphoma, Neoplasms

Acts on a complex — shared with RRM2B, RRM2 · 1 of 14 recorded protein targets — broad pharmacology

hydroxyurea
ApprovedInhibitor

Ribonucleoside-diphosphate reductase RR1 inhibitor

Indicated for Anemia, Sickle Cell, Carcinoma, Squamous Cell, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Melanoma

Acts on a complex — shared with RRM2B, RRM2 · 1 of 3 recorded protein targets — narrow recorded profile

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 RRM1

Gene-level evidence surfaced through the gene RRM1that 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.

Carcinoma, Non-Small-Cell Lung
0.77Well supported

Clinical evidence dominant · Open Targets 0.62

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

Clinical evidence dominant · Open Targets 0.59

Exocrine pancreatic carcinoma
0.72Moderately supported

Clinical evidence dominant · Open Targets 0.58

Ovarian carcinoma
0.71Moderately supported

Clinical evidence dominant · Open Targets 0.57

Neoplasms
0.70Moderately supported

Clinical evidence dominant · Open Targets 0.56

View evidence synthesis (5)
Carcinoma, Non-Small-Cell LungWell supported
0.77
agreement 0.630.90
Clinical85%Literature15%RNA expression0%

Open Targets aggregate 0.62 · 3 independent evidence families

Leukemia, Lymphocytic, Chronic, B-CellModerately supported
0.73
agreement 0.580.89
Clinical96%Literature4%

Open Targets aggregate 0.59 · 2 independent evidence families

Exocrine pancreatic carcinomaModerately supported
0.72
agreement 0.570.88
Clinical96%Literature4%

Open Targets aggregate 0.58 · 2 independent evidence families

Ovarian carcinomaModerately supported
0.71
agreement 0.570.84
Clinical94%Literature4%RNA expression2%

Open Targets aggregate 0.57 · 3 independent evidence families

NeoplasmsModerately supported
0.70
agreement 0.550.86
Clinical85%Literature15%

Open Targets aggregate 0.56 · 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
Carcinoma, Non-Small-Cell Lung0.62
Leukemia, Lymphocytic, Chronic, B-Cell0.59
Exocrine pancreatic carcinoma0.58
Ovarian carcinoma0.57
Melanoma0.56
Neoplasms0.56
Breast Neoplasms0.54
chronic myelogenous leukemia, BCR-ABL1 positive0.54

Drug development

10 compounds recorded · 7 approved · 3 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 (10)
TEZACITABINEPhase 2
GALLIUM NITRATEApproval
TRIAPINEPhase 3
TEZACITABINE ANHYDROUSPhase 2
GEMCITABINE HYDROCHLORIDEApproval
GEMCITABINEApproval
CLOFARABINEApproval
HYDROXYUREAApproval
FLUDARABINE PHOSPHATEApproval
MOTEXAFIN GADOLINIUMApproval

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.

Safety-related annotations

progression-free survivalClinPGxnauseaClinPGxneutropeniaClinPGx

Terms indexed against this target in Open Targets' safety data, with their datasource. These are annotations, not causal claims: the direction of effect (whether activation or inhibition is implicated), species and evidence strength are not captured here, so an entry does not mean that modulating this target is known to cause that condition.

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

6

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. Withdrawn from market2023-10-18

    Market withdrawal: Ivozall (EMA)

    ema · market · ema · via clofarabine

  2. New publication2017-10-19
    Novel use Of Hydroxyurea in an African Region with Malaria (NOHARM): a trial for children with sickle cell anemia.

    Blood · 2017 · 128 citations · Europe PMC · via hydroxyurea

  3. New publication2011-05-01
    Hydroxycarbamide in very young children with sickle-cell anaemia: a multicentre, randomised, controlled trial (BABY HUG).

    Lancet (London, England) · 2011 · 592 citations · Europe PMC · via hydroxyurea

  4. New publication2010-08-24
    Recruitment of infants with sickle cell anemia to a Phase III trial: data from the BABY HUG study.

    Contemporary clinical trials · 2010 · 34 citations · Europe PMC · via hydroxyurea

  5. 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

  6. Regulatory approval2006-05-29

    Approval: Evoltra (EMA)

    ema · regulatory · ema · via clofarabine

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.