Druggability & Clinical Context
Druggability
Medium
Score: 0.61
Druggability Analysis
Structural Tractability0.95
Key Metrics
PDB Structures:
61
Known Drugs:
2
Approved:
2
In Clinical Trials:
0
Drug Pipeline (2 compounds)
2 Approved
Therapeutic Areas:Multiple myeloma Alzheimer's disease Parkinson's disease Age-related neurodegeneration NAD+ metabolism disorders Cognitive decline Other hematologic malignancies
Druggability Rationale: CD38 is highly druggable (0.90 score) due to its well-characterized catalytic site, extensive structural data (61 PDB structures at 1.45 Å resolution), and proven clinical validation with two approved monoclonal antibodies (daratumumab, isatuximab) demonstrating target engagement. The enzyme's defined NAD+ binding pocket and established mechanism make it amenable to both antibody and small molecule inhibitor approaches.
Mechanism: Monoclonal antibody targeting or small molecule inhibitor of NAD+ consuming activity
Drug Pipeline (2 compounds)
2 Approved
Known Drugs:Daratumumab (approved) — Multiple myeloma
Isatuximab (approved) — Multiple myeloma
Structural Data:PDB (61) ✓AlphaFold ✓Cryo-EM ✓
Binding Pocket Analysis:The NAD+ binding pocket is well-characterized across 61 crystal structures, featuring a defined active site with metal coordination (typically Zn2+) and substrate recognition elements that accommodate the adenosine and ribose moieties. Monoclonal antibody epitopes are mapped on the extracellular domain, while small molecule inhibitors target the catalytic cleft accessible from the cell surface.
Selectivity & Safety Considerations
CD38 has limited tissue selectivity concerns as a single gene target, but selectivity challenges may arise from its dual catalytic activities (ADP-ribosyl cyclase and cyclic ADP-ribose hydrolase) requiring differentiated inhibition. Off-target risks for small molecule inhibitors include related ADP-ribosyl cyclases (CD157/BST-1), necessitating careful structural design to avoid cross-reactivity.
Clinical Trials (8)
Relevant trials from ClinicalTrials.gov
By Phase
PHASE1: 2 · PHASE2: 5 · PHASE3: 1
PHASE3
NCT06918002
n=824
Multiple Myeloma, Newly Diagnosed
Interventions: Elranatamab, Lenalidomide (Revlimid®), Daratumumab SC (Darzalex)
Sponsor: Intergroupe Francophone du Myelome | Started: 2025-07-09
PHASE2
NCT06140966
n=54
Multiple Myeloma, Primary Plasma Cell Leukemia, Extramedullary Multiple Myeloma
Interventions: Daratumumab, Carfilzomib, Lenalidomide
Sponsor: Union Hospital, Tongji Medical College, Huazhong University | Started: 2023-10-20
PHASE2
NCT06860269
n=1200
Acute Lymphoblastic Leukemia
Interventions: Randomization + Blinatumomab + chemother, Randomization + Standard frontline T-ALL, Randomization + Isatuximab + Standard fr
Sponsor: Assistance Publique - Hôpitaux de Paris | Started: 2025-05-06
PHASE2
NCT05665140
n=100
Newly Diagnosed Multiple Myeloma
Interventions: Isatuximab, Lenalidomide, Bortezomib
Sponsor: University Hopsital Schleswig Holstein Campus Lübeck | Started: 2023-02-03
PHASE2
NCT04786028
n=72
Multiple Myeloma
Interventions: Isatuximab
Sponsor: Canadian Myeloma Research Group | Started: 2021-12-08
PHASE2
NCT04835129
n=28
Multiple Myeloma
Interventions: Isatuximab (for run-in portion), Isatuximab (for expansion), Pomalidomide
Sponsor: Medical College of Wisconsin | Started: 2022-01-10
PHASE1
NCT04722146
n=140
Multiple Myeloma
Interventions: Teclistamab, Daratumumab, Pomalidomide
Sponsor: Janssen Research & Development, LLC | Started: 2021-03-12
PHASE1
NCT02918331
n=7
Multiple Myeloma
Interventions: Daratumumab (16 mg/kg), Lenalidomide, Dexamethasone
Sponsor: Janssen Pharmaceutical K.K. | Started: 2016-09