NPM1 nucleophosmin 1
ENSG00000181163 · protein coding · Open Targets profile
Involved in diverse cellular processes such as ribosome biogenesis, centrosome duplication, protein chaperoning, histone assembly, cell proliferation, and regulation of tumor suppressors p53/TP53 and ARF. Binds ribosome presumably to drive ribosome nuclear export. Associated with nucleolar ribonucleoprotein structures and bind single-stranded nucleic acids. Acts as a chaperonin for the core histones H3, H2B and H4. Stimulates APEX1 endonuclease activity on apurinic/apyrimidinic (AP) double-stranded DNA but inhibits APEX1 endonuclease activity on AP single-stranded RNA. May exert a control of APEX1 endonuclease activity within nucleoli devoted to repair AP on rDNA and the removal of oxidized rRNA molecules. In concert with BRCA2, regulates centrosome duplication. Regulates centriole duplication: phosphorylation by PLK2 is able to trigger centriole replication. Negatively regulates the activation of EIF2AK2/PKR and suppresses apoptosis through inhibition of EIF2AK2/PKR autophosphorylation. Antagonizes the inhibitory effect of ATF5 on cell proliferation and relieves ATF5-induced G2/M blockade (PubMed:22528486). In complex with MYC enhances the transcription of MYC target genes (PubMed:25956029). May act as chaperonin or cotransporter in the nucleolar localization of transcription termination factor TTF1 (By similarity). {ECO:0000250|UniProtKB:Q61937, ECO:0000269|PubMed:12882984, ECO:0000269|PubMed:16107701, ECO:0000269|PubMed:17015463, ECO:0000269|PubMed:18809582, ECO:0000269|PubMed:19188445, ECO:0000269|PubMed:20352051, ECO:0000269|PubMed:21084279, ECO:0000269|PubMed:22002061, ECO:0000269|PubMed:22528486, ECO:0000269|PubMed:25956029}.
Each band is a group of drugs. It runs from the kind of drug on the left to the furthest stage that drug has reached in any disease on the right. Thicker bands mean more drugs.
Approved bands are highlighted. Withdrawn means the drug was pulled from the market or from development. A combined phase counts as the later one (Phase 1/2 is shown as Phase 2). Hover a band for the drug names. Source: Open Targets Platform, fetched live.
Each row is a cancer, strongest overall evidence first. The two dots show how strong the inherited (germline) and tumour-mutation (somatic) evidence is; the line between them is the gap.
Scores run from 0 (no evidence) to 1 (strongest). A missing dot at 0 means Open Targets holds no evidence of that kind. Source: Open Targets Platform, fetched live.
Tractability
- Small molecule
- Approved Drug, Structure with Ligand, High-Quality Ligand, Druggable Family
- PROTAC
- UniProt Ubiquitination, Database Ubiquitination, Half-life Data, Small Molecule Binder
gnomAD loss of function constraint: o/e 0.022662000730633736 (upper bound 0.10751000046730042). Low values mean loss of function is poorly tolerated, a safety flag for inhibition.
Who runs trials of these drugs
Principal investigators and study chairs on 78 registry trials, updated in the last three years, of the most advanced drugs against NPM1 (crizotinib, ceritinib), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- Yongchang ZhangHunan Cancer Hospital · 3 of 3 trials Phase 2+
- Caicun ZhouShanghai East Hospital · 2 of 2 trials Phase 2+
- David S HongECOG-ACRIN Cancer Research Group · 2 of 2 trials Phase 2+
- Aaron S MansfieldECOG-ACRIN Cancer Research Group · 1 of 1 trials Phase 2+
- Alex MenziesMelanoma Institute Australia · 1 of 1 trials Phase 2+
- Alice T ShawECOG-ACRIN Cancer Research Group · 1 of 1 trials Phase 2+
- Antoine ItalianoInstitut Bergonié · 1 of 1 trials Phase 2+
- Åslaug HellandOslo University Hospital · 1 of 1 trials Phase 2+
- Daniel J RenoufBCCA - Vancouver Cancer Centre, Vancouver BC, Canada · 1 of 1 trials Phase 2+
- David GerberECOG-ACRIN Cancer Research Group · 1 of 1 trials Phase 2+
- E.E. VoestThe Netherlands Cancer Institute · 1 of 1 trials Phase 2+
- Eric J LoweChildren's Oncology Group · 1 of 1 trials Phase 2+
- Gary W MiddletonUniversity of Birmingham · 1 of 1 trials Phase 2+
- George Cole Jr.gcole@ideayabio.com · 1 of 1 trials Phase 2+
- Gilles VASSALGustave Roussy, Villejuif · 1 of 1 trials Phase 2+
Registry trials of crizotinib, ceritinib updated in the last three years, counted by the country group of their listed sites. A trial with sites in several groups counts in each; 46 of 76 have all sites in one country.
Site counts are not patients per country, and trials registered only outside ClinicalTrials.gov are not covered. Where sites are is a fact about the record, not a judgement of its quality. Europe is the EU and EEA, the UK and Switzerland. 2 trials list no sites and are left out. Source: ClinicalTrials.gov, fetched live.
30 trials of drugs against NPM1 were stopped early; 6 give no reason
Terminated, withdrawn and suspended interventional trials of crizotinib, ceritinib, newest update first, live from ClinicalTrials.gov. Each reason is quoted exactly as the registry gives it; we do not sort reasons into safety, efficacy or business. Dates are the last registry update. Showing the 25 most recent of 30.
- suspended · 2026-06-05 · Megan Kruse, MD · matched by the registry's drug synonyms“Anheart acquired by Nuvation Bio; leadership not moving forward”
- terminated · 2026-04-23 · National Cancer Institute (NCI) · Ceritinib, Crizotinib“Inadequate accrual rate”
- terminated · 2026-03-10 · Yael P Mosse · Ceritinib“The goals of Part 1 (molecular screening) were met, but lack of therapies to match molecular aberrations made Part 2 (treatment) no longer feasible.”
- terminated · 2025-07-16 · National Cheng-Kung University Hospital · Crizotinib 250 MG“Patients were recruited during screen phase but fewer patients met criteria.”
- terminated · 2025-01-23 · Pfizer · Crizotinib“Termination of further treatment on the study due to the availability of commercial supply or a rollover study (NCT05160922) that will allow active subjects to continue receiving treatment.”
- terminated · 2024-11-08 · Pfizer · Crizotinib“The trial is terminated based on business decision, not due to safety concerns or regulatory requirements.”
- terminated · 2024-04-26 · Suzhou Zelgen Biopharmaceuticals Co.,Ltd · matched by the registry's drug synonyms“Sponsor R\&D Strategy Adjustment”
- terminated · 2023-07-07 · Pfizer · Crizotinib“The study was terminated since there was no need for further safety or efficacy data to be collected. The participants having benefit from the Investigational treatments have been moved to a continuation study (NCT05059522)”
- terminated · 2023-02-03 · University of Texas Southwestern Medical Center · Ceritinib“The study was terminated after UTSW was informed by Novartis that further support for the study would not be provided”
- terminated · 2022-12-27 · University of California, San Francisco · Ceritinib“Low Accrual”
- terminated · 2022-11-03 · Wake Forest University Health Sciences · Crizotinib“Study closed to accrual due to low accrual numbers.”
- terminated · 2022-10-24 · University of Colorado, Denver · matched by the registry's drug synonyms“Low accrual”
- terminated · 2021-09-13 · M.D. Anderson Cancer Center · Crizotinib (Xalkori)“PI request”
- terminated · 2021-04-08 · Novartis Pharmaceuticals · Ceritinib“Study was terminated due to low enrollment”
- terminated · 2020-02-20 · SWOG Cancer Research Network · crizotinib“science has moved forward and there is no intent to complete the study”
- terminated · 2020-01-27 · University of California, San Francisco · Ceritinib“Funding”
- terminated · 2019-12-27 · Novartis Pharmaceuticals · Ceritinib (LDK378)No reason given
- terminated · 2019-12-17 · National Cancer Institute (NCI) · matched by the registry's drug synonymsNo reason given
- withdrawn · 2019-10-10 · University of Washington · Ceritinib“Administrative closure”
- terminated · 2019-08-05 · National Cancer Institute (NCI) · CrizotinibNo reason given
- withdrawn · 2019-07-30 · University of Texas Southwestern Medical Center · Ceritinib“study was on hold for protocol redesign; decided to not move forward with study.”
- terminated · 2019-07-01 · Pfizer · Crizotinib“Decision based on the low enrollment mainly due to high efficacy drugs available in 1st line ALK-positive NSCLC (eg alectinib), not due to any safety concerns”
- terminated · 2018-04-05 · National Health Research Institutes, Taiwan · matched by the registry's drug synonyms“ROS1 in IHC and gene rearrangement result can not match。No tumor response。”
- terminated · 2018-04-02 · Criterium, Inc. · ceritinib“Lack of Enrollment”
- terminated · 2017-08-09 · Mothaffar Rimawi · Crizotinib & Sunitinib 37.5 mg Cohort 3“Poor accrual so the study was halted on May 16, 2017.”
Paediatric incentives and obligations for NPM1's drugs
For crizotinib, ceritinib: what EMA and FDA publish about paediatric plans, orphan status and pediatric approvals, and how many registered studies take children. Each line is a yes, no or not published fact from the record linked under it; none of it is a forecast.
- FDA pediatric target list: no · NPM1 is not on the listRule: Target is on FDA's Pediatric Molecular Target List (relevant targets). Source: FDA Pediatric Molecular Target List (Listed as February 2026 on the FDA Pediatric Oncology page; the file served is 9.7.22_the_relevant_molecular_target_list.xlsx, whose Summary of Changes sheet is headed 'SEPTEMBER 2022 UPDATE' (footnote date 2022-09-01)), 2026-11-11
- EU paediatric investigation plan: yes · EMEA-001493-PIP03-18-M01 (crizotinib, Treatment of anaplastic large cell lymphoma;Treatment of inflammatory myofibroblastic tumours): PM: decision on the application for modification of an agreed PIP, 27 Jan 2021; compliance positive 31 Mar 2023; EMEA-001493-PIP02-18 (crizotinib, Treatment of lung malignant neoplasms): W: decision granting a waiver in all age groups for all conditions or indications, 7 Dec 2018Rule: An EMA PIP decision (agreement, modification or waiver) lists the drug as its active substance, exact name. Source: EMA data download (dated snapshot), 2026-11-11
- EU orphan designation: no · No EU orphan designation names crizotinib, ceritinibRule: An EU orphan designation lists the drug as its active substance (exact name) or belongs to a medicine that does; withdrawn and expired designations are listed with their status. Source: EMA data download (dated snapshot), 2026-11-11
- Authorised in the EU: yes · Xalkori: authorised since 23 Oct 2012; Zykadia: authorised since 6 May 2015Rule: An EMA medicine record lists the drug as its active substance or INN, exact name; national-only authorisations are not in this file. Source: EMA data download (dated snapshot), 2026-11-11
- FDA orphan designation: not published · FDA's orphan designation database turns away automated requests, so this app does not read it; search it by hand at the linkRule: Would be: an FDA orphan designation names the drug. Source: FDA orphan designations search
- FDA pediatric oncology approval: yes · Crizotinib [Xalkori], 14 Jul 2022: Treatment of adult and pediatric patients 1 year of age and older with unresectable, recurrent, or refractory inflammatory myofibroblastic tumor (IMT) that is ALK-positive; Crizotinib [Xalkori], 14 Jan 2021: Treatment of pediatric patients 1 year of age and older and young adults with relapsed or refractory, systemic anaplastic large cell lymphoma (ALCL) that is ALK-positiveRule: FDA's Pediatric Oncology Drug Approvals table names the drug. Source: FDA Pediatric Oncology Drug Approvals (content current as of 2026-03-03), 2026-11-11
- Registered studies open to children: yes · 23 interventional studies of crizotinib, ceritinib include patients under 18; 5 are recruiting, not yet recruiting or activeRule: The registry's age group includes Child (birth to 17 years), which also counts studies that set no minimum age. Source: ClinicalTrials.gov search, 2026-11-11
Rare pediatric disease voucher. FDA, content current as of 29 Apr 2026: “As of February 3, 2026, enactment of the Consolidated Appropriations Act, 2026, the rare pediatric disease PRV program will sunset after September 30, 2029. FDA may not award any PRVs under this program after September 30, 2029.” Voucher sale prices are not shown here; they appear only as company-reported news. FDA: Rare Pediatric Disease Designation and Priority Review Voucher Programs
All 2 drugs and clinical candidates as a table
Each drug, stage and indication links to its Open Targets record, where the trials and approvals behind it are listed. Salt forms (for example a mesylate) are listed as Open Targets records them, as separate entries.