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Protein / target

ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1

Encoded byCD38P28907Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
2
Approved medicines
Open Targets target-level
View by indication →
30
Clinical trials
Small-molecule tractable
Druggability
Structure with Ligand

Protein at a glance

Biological role

NAD+ nucleosidase activity, cyclic ADP-ribose generating

Strongest disease association

Parkinson's Disease

Via encoding gene CD38 · Genetic evidence · score 0.72

Therapeutic position

Established drug target

Antibodies

Research activity

Emerging research

3 papers · latest 2024

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

Multifunctional transmembrane glycoprotein able to exert enzymatic activities and also to mobilize calcium, to transduce signals, to adhere to hyaluronan and to other ligands.

View complete UniProt function annotation

Multifunctional transmembrane glycoprotein able to exert enzymatic activities and also to mobilize calcium, to transduce signals, to adhere to hyaluronan and to other ligands. Synthesizes cyclic ADP-ribose (cADPR), a second messenger for glucose-induced insulin secretion (PubMed:7961800, PubMed:8253715). Synthesizes the Ca(2+) mobilizer nicotinate-adenine dinucleotide phosphate, NAADP(+), from 2'-phospho-cADPR and nicotinic acid, as well as from NADP(+) and nicotinic acid. At both pH 5.0 and pH 7.4 preferentially transforms 2'-phospho-cADPR into NAADP(+), while preferentially cleaving NADP(+) to cADPR and ADPRP rather than into NADDP(+) (PubMed:16690024). Has cADPR hydrolase activity (PubMed:7961800, PubMed:8253715). Functions also as a receptor that binds the ligand CD31 on endothelial cells, promoting lymphocyte activation, proliferation, and migration across the endothelial barrier (PubMed:9551996). Involved in the regulation of crucial dendritic cell functions acquired at the mature stage, such as CCL21-driven migration, survival, and Th1-polarizing activity (PubMed:16293598). In lamina propria T lymphocytes, CD38/CD31 cognate interactions initiate a multistep signaling pathway resulting in activation of LCK anf LAT, followed by cytokine release (PubMed:11259373)

Subcellular location

Cell surfaceCell membrane
Domains and Gene Ontology detail (36)

Gene Ontology

  • Cbasolateral plasma membrane
  • Ccell surface
  • Cextracellular exosome
  • Cmembrane
  • Cnuclear membrane
  • Cplasma membrane
  • Fidentical protein binding
  • FNAD+ nucleosidase activity, cyclic ADP-ribose generating
  • Fphosphorus-oxygen lyase activity
  • Fsignaling receptor activity
  • Ftransferase activity
  • Papoptotic signaling pathway

300 aa · 34 kDa · 2 isoforms

Biological roles

Reactome v97

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

Immune signallingUniProt · GOMetabolic enzyme activityGOTranscriptional regulationGO
View supporting evidence

Immune signalling

  • ·Multifunctional transmembrane glycoprotein able to exert enzymatic activities and also t…
  • ·B cell receptor signaling pathway
  • ·positive regulation of B cell proliferation
  • ·response to interleukin-1

Metabolic enzyme activity

  • ·transferase activity
  • ·nicotinate metabolic process

Transcriptional regulation

  • ·negative regulation of DNA-templated transcription
  • ·positive regulation of DNA-templated transcription
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.

PECAM1CD34NAMPTNMNAT1CD19SIRT1NMNAT2SIRT3CD4ENPP1CD38

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

2 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 Myeloma2 medicines
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.

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.

daratumumab
Narrow target profileApprovedInhibitor

Lymphocyte differentiation antigen CD38 inhibitor

Indicated for Multiple Myeloma, Neoplasms

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

isatuximab
Narrow target profileApprovedInhibitor

Lymphocyte differentiation antigen CD38 inhibitor

Indicated for Multiple Myeloma, Neoplasms

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 CD38

Gene-level evidence surfaced through the gene CD38that 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.

Multiple Myeloma
0.78Well supported

Clinical evidence dominant · Open Targets 0.63

Parkinson's Disease
0.75Well supported

Genetic evidence dominant · Open Targets 0.46

Neoplasms
0.63Moderately supported

Clinical evidence dominant · Open Targets 0.49

Self-injurious ideation
0.47Limited support

Genetic evidence dominant · Open Targets 0.29

Smoldering plasma cell myeloma
0.45Limited support

Clinical evidence dominant · Open Targets 0.36

View evidence synthesis (5)
Multiple MyelomaWell supported
0.78
agreement 0.620.93
Clinical84%Literature16%

Open Targets aggregate 0.63 · 2 independent evidence families

Parkinson's DiseaseWell supported
0.75
agreement 0.610.89
Genetic87%Literature14%

Open Targets aggregate 0.46 · 2 independent evidence families

NeoplasmsModerately supported
0.63
agreement 0.480.79
Clinical79%Literature21%

Open Targets aggregate 0.49 · 2 independent evidence families

Self-injurious ideationLimited support
0.47
agreement 0.350.59
Genetic100%

Open Targets aggregate 0.29 · 1 independent evidence family

Smoldering plasma cell myelomaLimited support
0.45
agreement 0.290.60
Clinical99%Literature1%

Open Targets aggregate 0.36 · 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
Multiple Myeloma0.63
Neoplasms0.49
Parkinson's Disease0.46
Smoldering plasma cell myeloma0.36
Purpura, Thrombocytopenic, Idiopathic0.35
Immunoglobulin Light-chain Amyloidosis0.32
Self-injurious ideation0.29
Leukemia0.28
Acute leukemia0.26
Autoimmune Diseases of the Nervous System0.26

Drug development

4 compounds recorded · 2 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 (4)
ISATUXIMABApproval
FELZARTAMABPhase 3
DARATUMUMABApproval
MEZAGITAMABPhase 3

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 moleculesEmerging

Feasibility evidence (structure with ligand and high-quality ligand) — no clinical-stage drug of this modality recorded.

AntibodiesStrong

Approved Drug and UniProt loc high conf 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 (11)
SM · Structure with LigandSM · High-Quality LigandSM · High-Quality PocketAB · Approved DrugAB · UniProt loc high confAB · GO CC high confAB · UniProt SigP or TMHMMAB · Human Protein Atlas locPR · Database UbiquitinationPR · Half-life DataPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

Safety-related annotations

regulation of gene expressionToxCast

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)

ACTIVE_NOT_RECRUITING · via daratumumab · NCT05438043

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 daratumumab

  2. Trial status changed2026-07-23

    Randomized Phase 2 Trial of Isatuximab During Autologous Stem Cell Collection and Transplantation Period in Patients With Multiple Myeloma, Relapsed Hodgkin's and Non-Hodgkin's Lymphoma

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

  3. Regulatory approval2026-07-09

    Approval: ISATUXIMAB-IRFC (BLA761445)

    fda · regulatory · fda · via isatuximab

  4. Label change2026-06-26

    Label change: ISATUXIMAB (BLA761113)

    fda · regulatory · fda · via isatuximab

  5. Indication expanded2024-10-25

    Indication expansion: ISATUXIMAB (BLA761113)

    fda · regulatory · fda · via isatuximab

  6. Indication expanded2024-10-25

    Indication expansion: ISATUXIMAB (BLA761113)

    fda · regulatory · fda · via isatuximab

  7. Indication expanded2024-09-20

    Indication expansion: ISATUXIMAB (BLA761113)

    fda · regulatory · fda · via isatuximab

  8. New publication2024-06-15
    Bortezomib, thalidomide, and dexamethasone with or without daratumumab and followed by daratumumab maintenance or observation in transplant-eligible newly diagnosed multiple myeloma: long-term follow-up of the CASSIOPEIA randomised controlled phase 3 trial.

    The Lancet. Oncology · 2024 · 90 citations · Europe PMC · via daratumumab

  9. New publication2021-09-13
    Maintenance with daratumumab or observation following treatment with bortezomib, thalidomide, and dexamethasone with or without daratumumab and autologous stem-cell transplant in patients with newly diagnosed multiple myeloma (CASSIOPEIA): an open-label, randomised, phase 3 trial.

    The Lancet. Oncology · 2021 · 143 citations · Europe PMC · via daratumumab

  10. New publication2021-02-15
    Daratumumab monotherapy for patients with relapsed or refractory natural killer/T-cell lymphoma, nasal type: an open-label, single-arm, multicenter, phase 2 study.

    Journal of hematology & oncology · 2021 · 55 citations · Europe PMC · via daratumumab

  11. Safety communication2019-08-19

    Drug Safety Update: Daratumumab (Darzalex▼): risk of reactivation of hepatitis B virus

    mhra · safety · mhra · via daratumumab

  12. New publication2019-06-03
    Bortezomib, thalidomide, and dexamethasone with or without daratumumab before and after autologous stem-cell transplantation for newly diagnosed multiple myeloma (CASSIOPEIA): a randomised, open-label, phase 3 study.

    Lancet (London, England) · 2019 · 725 citations · Europe PMC · via daratumumab

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.

Research activity

3 papers · to 2024

Papers linked directly to this protein. This is the protein's own literature — descriptor-derived papers are kept separate below.

Most cited

van de Donk NWCJ · Blood · 2018

Bocuzzi V · Journal of translational medicine · 2024

Recent

Europe PMC papers linked directly to this protein.