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Inflammatory myofibroblastic tumor

GtoPdb Disease Summaries

This section gives an overview of the disease, and where available shows the following:

  • Synonyms: Shows known synonyms for the disease.
  • Description: Gives a basic description/definition of the disease.
  • Database Link: External links to the same disease at the Disease Ontology, OMIM or Orphanet sites.
  • Immunopharmacology comments: General comments about the target's role in immunopharmacology, provided by GtoImmuPdb curators.
  • Associated with: Counts are displayed for the total targets the disease is associated with in GtoPdb. The counts of targets and ligands of immunological relevance associated to the disease are also shown.

More information can be found in the help pages.

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Disease ID:495
Name:Inflammatory myofibroblastic tumor
Associated with:1 target
1 immuno-relevant ligand
Database Links
Orphanet: ORPHA178342

Targets

GtoPdb Disease Summaries - Targets

Click on the target name to link to its detailed view page

Where available, information is display on the role of the target in the disease; drugs which target the disease and their therapeutic use and side-effects.

If there is mutation data curated in GtoPdb this is indicated, with a link back to the appropriate section on the target detailed view page

Immuno ligand interactions - If available, a table of immuno-relevant ligands is shown. These ligands have been curated as having an association to the disease and possess interaction data with the target in GtoPdb. The approval status of the ligand is shown, along with curator comments and an indication of whether the target is considered the primary target of the ligand.

More information can be found in the help pages.

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Key to terms and symbols
ALK receptor tyrosine kinase
Ligand interactions: 
Ligand Comments
crizotinib
Crizotinib is an approved drug for the treatment of unresectable, recurrent, or refractory ALK+ve inflammatory myofibroblastic tumours

Ligands

GtoPdb Disease Summaries - Ligands

Click ligand name to view ligand summary page

  • Approved: If the ligand is an approved drug this is indicated, along with approval bodies.
  • Immuno: Immuno icon indicates the ligand is immuno-relevant

Click the arrow in the final column to expand comments

  • Immuno Disease Comments: Curatorial comments specifically added as part of GtoImmuPdb. They give more information on the association between the ligand and disease in the context of immunopharmacology.
  • Clinical Use: General clinical comments relating to the ligand and may not necessarily be specific to the disease in question. With hyperlink to more details on the ligand summary pages.
  • Bioactivty Comments: Curatorial comments specifically about the compounds biological activity - with hyperlink to more details on the ligand summary pages.

More information can be found in the help pages.

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Key to terms and symbols Click ligand name to view ligand summary Click column headers to sort
Ligand References Clinical and Disease comments
crizotinib
Immuno Disease Comments: Crizotinib is an approved drug for the treatment of unresectable, recurrent, or refractory ALK+ve inflammatory myofibroblastic tumours
Clinical Use: Crizotinib was originally approved for treatment of anaplastic lymphoma kinase (ALK)-positive non-small cell lung carcinomas (NSCLC).
In March 2016, the US FDA expanded marketing authorisation to include treatment of patients with ROS1-positive metastatic NSCLC. Clinical trials for anaplastic large cell lymphoma, neuroblastoma, and other advanced solid tumours are ongoing.
In mid-2018, the FDA granted breakthrough designations for Xalkori as a treatment for NSCLC with MET exon 14 alterations (and with disease progression on or after platinum-based chemotherapy), and as a treatment for ALK-positive relapsed/refractory systemic anaplastic large cell lymphoma. Approval was expanded further in July 2022, when crizotinib was granted FDA approval as a treatment for unresectable, recurrent, or refractory inflammatory ALK-positive myofibroblastic tumours. | View clinical data
Bioactivity Comments: The (S)-enantiomer () is considerably less potent than the (R)-enantiomer against its established protein kinase targets [1]. Interestingly, (S)-crizotinib has been reported to inhibit the activity of NUDT1 (P36639) with a Kd of 48nM [1]. NUDT1 is an antimutagenic enzyme involved in the effective elimination of oxidised nucleotides (induced by oxidative stress, for example), thus preventing their incorporation into DNA. At this target the (R)-enantiomer is the less potent enantiomer (Kd 781nM). This highlights the necessity that drug compounds be steroespecifically pure when there is a pharmacological difference in activity between stereoisomers (ie they exhibit distinct molecular mechanisms of action), as enantiomerically impure mixtures may result in off-target effects.
A number of chemical suppliers and other submitters to online chemistry databases specify the non-stereoisomeric molecule depicted in PubChem CID 11597571. | View biological activity

References

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1. Huber KV, Salah E, Radic B, Gridling M, Elkins JM, Stukalov A, Jemth AS, Göktürk C, Sanjiv K, Strömberg K et al.. (2014) Stereospecific targeting of MTH1 by (S)-crizotinib as an anticancer strategy. Nature, 508 (7495): 222-7. [PMID:24695225]