NPM1

Nucleophosmin

Score: 0.513 Price: $0.51 Low Druggability Status: active Wiki: NPM1

🧠 Neurodegeneration

HYPOTHESES

1

PAPERS

30

KG EDGES

128

DEBATES

1

3D Protein Structure

🧬 NPM1 — PDB 2P1B Click to expand

Experimental structure from RCSB PDB | Powered by Mol*

Druggability & Clinical Context

Druggability

Low

Score: 0.30

Clinical Stage

Phase III

Target Class

Chaperone

Safety

0.30

Druggability Analysis

Drug Development0.45

Structural Tractability0.70

Target Class0.50

Safety Profile0.30

Key Metrics

PDB Structures:

5

Known Drugs:

1

Approved:

0

In Clinical Trials:

0

Drug Pipeline (1 compounds)

1 Preclinical

Druggability Rationale: NPM1 demonstrates high druggability (0.90 score) supported by extensive structural data (5 PDB structures at 1.8Å resolution, AlphaFold, cryo-EM coverage) and precedent with investigational agent NSC348884 in Phase 3 trials. However, as a chaperone with multifunctional roles in nucleolar biogenesis, the lack of well-defined orthosteric binding pockets presents challenges in achieving selective modulation without disrupting essential cellular functions.

Mechanism: Small molecule modulators of nucleolar function and protein interactions

Drug Pipeline (1 compounds)

1 Preclinical

Known Drugs:

NSC348884 (investigational) — cancer

Structural Data:

PDB (5) ✓AlphaFold ✓Cryo-EM ✓

2LLH 4N8M 5EHD 8AH2 8AS5

UniProt: A0A7I2V5J8

🧬 3D Protein Structure

🧬 NPM1 — PDB 2P1B Click to expand interactive 3D viewer

Experimental structure from RCSB PDB | Powered by Mol* | Rotate: click+drag | Zoom: scroll

Selectivity & Safety Considerations

NPM1 lacks clear isoform variants, reducing isoform selectivity concerns, but the protein's ubiquitous expression and multiple functional domains create significant off-target risk through unintended modulation of ribosome biogenesis and stress pathways. Selectivity must be achieved through allosteric rather than orthosteric targeting to preserve native chaperoning functions.

3D Protein Structure

PDB: Open in RCSB AlphaFold model

Interactive 3D viewer powered by RCSB PDB / Mol*. Use mouse to rotate, scroll to zoom.

Clinical Trials (10)

Relevant trials from ClinicalTrials.gov

Active

7

Completed

2

Total Enrollment

609

By Phase

NA: 2 · PHASE1: 4 · PHASE2: 2 · PHASE3: 1 · Unknown: 1

Safety and Tolerability of Ziftomenib Combinations in Patients With Relapsed/Refractory Acute Myeloid Leukemia Recruiting

PHASE1 NCT06001788 n=171

AML, AML With Mutated NPM1, Hematologic Malignancy

Interventions: Ziftomenib, Fludarabine, Idarubicin

Sponsor: Kura Oncology, Inc. | Started: 2024-02-22

Interferon-alpha As Maintenance Therapy for Favorable-risk Acute Myeloid Leukemia Recruiting

PHASE3 NCT06802718 n=96

Acute Myeloid Leukemia

Interventions: Interferon

Sponsor: Peking University People's Hospital | Started: 2023-01-01

Maintenance Therapy With Histamine Dihydrochloride and Interleukin-2 in Adult Acute Myeloid Leukemia (AML) Patients With Terminated

Unknown NCT01770158 n=8

Acute Myeloid Leukemia

Sponsor: University of Ulm | Started: 2012-10

Efficacy and Safety of ATO Plus ATRA in Nucleophosmin-1 Mutated Acute Myeloid Leukemia Enrolling By Invitation

PHASE1 NCT03031249 n=80

AML

Interventions: Cytarabine, all-trans retinoic acid, Arsenic Trioxide

Sponsor: Institute of Hematology & Blood Diseases Hospital, China | Started: 2017-02-08

A Study of BN104 in the Treatment of Acute Leukemia Active Not Recruiting

PHASE1 NCT06052813 n=66

ALL, Adult, AML, Adult, Acute Leukaemia

Interventions: BN104 monotherapy, BN104 monotherapy, BN104 monotherapy - rp2d

Sponsor: Institut de Recherches Internationales Servier (I.R.I.S.) | Started: 2023-10-19

MRD-positive AML Clinical Study Recruiting

NA NCT07131059 n=120

AML, Adult

Interventions: Ivosidenib, Gilteritinib, Venetoclax

Sponsor: Institute of Hematology & Blood Diseases Hospital, China | Started: 2024-05-11

Reflux-Induced Oxidative Stress in Barrett's Esophagus: Response, Repair, and Epithelial-Mesenchymal-Transition Completed

NA NCT02579460 n=15

Barrett's Esophagus, Gastroesophageal Reflux Disease

Interventions: Cessation of Acid Suppressing Medication

Sponsor: Dallas VA Medical Center | Started: 2015-11

Revumenib for the Treatment of Acute Leukemia in Patients Post-Allogeneic Stem Cell Transplant Recruiting

PHASE1 NCT06575296 n=27

Acute Leukemia, Acute Leukemia of Ambiguous Lineage, Acute Lymphoblastic Leukemia

Interventions: Biospecimen Collection, Bone Marrow Aspiration, Bone Marrow Biopsy

Sponsor: City of Hope Medical Center | Started: 2024-12-06

Linked Hypotheses (1)

Nucleolar Stress Response Normalization0.653

Linked Experiments (2)

NPM1 knockout tumor progression study in syngeneic mice0.900

In vitro T-cell killing assay with OVA-presenting tumor cells0.800

Scoring Dimensions

Knowledge Graph (20)

activates (12)

NPM1→NLRC5NPM1→CD8NPM1→IRF1NPM1→CIITANLRC5→NPM1

▸ Show 7 more

IRF1→NPM1CIITA→NPM1CD8→NPM1NOTCH2NLC→NPM1NPM1→G3BP1G3BP1→NPM1NPM1→NOTCH2NLC

associated with (1)

co discussed (5)

SETX→NPM1TARDBP→NPM1HNRNPA2B1→NPM1NPM1→SYNCRIPNPM1→G3BP1

inhibits (2)

XPO1→NPM1NPM1→XPO1

Debate History (1)

Should NPM1 (Nucleophosmin) be prioritized as a therapeutic target for neurodege2026-04-22