Synonyms: Ogsiveo® | PF-03084014 | PF3084014 | Z-3181
nirogacestat is an approved drug (FDA (2023))
Compound class:
Synthetic organic
Comment: Nirogacestat (PF-3084014) is compound 14f in [2] where it is described as a centrally active γ-secretase inhibitor. It is a reversible, non-competitive, and orally bioactive agent. It was proposed an an anti-tumour agent [1,3,10-11].
PF-3084014 was also reported as an inhibitor of the NOTCH signalling pathway which bolstered its oncology credentials [7,10], since NOTCH inhibition promotes cell cycle arrest and induces apoptosis in tumour cells. Ligand Activity Visualisation ChartsThese are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts. ✖ |
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No information available. |
Summary of Clinical Use |
This compound was assessed in clinical trials for the treatment of several types of cancer. Click here to view the full list of PF-03084014 trials registered with ClinicalTrials.gov. A number of PF-03084014 clinical trials appear to have been stopped or withdrawn, apparently for business reasons. Notes against these trials state that there were no safety/efficacy concerns behind the decisions. Development for desmoid tumours [8] (a rare and aggressive soft tissue sarcoma) was continued by SpringWorks Therapeutics. There were no FDA-approved treatments for desmoid tumours at the time. Based on efficacy data coming from clinical trials [9], nirogacestat was granted FDA orphan designation for this indication in mid-2018. EMA orphan drug designation followed in late 2019. In 2023, the FDA accepted nirogacestat for priority review as a treatment option for locally invasive, soft tissue desmoid tumours, and this culminated in full approval in November of that year [6]. Nirogacestat (Ogsiveo) was the first approved drug to reach the clinic as a treatment for desmoid tumours. |
Clinical Trials | |||||
Clinical Trial ID | Title | Type | Source | Comment | References |
NCT04195399 | A Study of a New Drug, Nirogacestat, for Treating Desmoid Tumors That Cannot be Removed by Surgery | Phase 2 Interventional | Children's Oncology Group | ||
NCT01981551 | Phase II Trial of the Gamma-Secretase Inhibitor PF-03084014 in Adults With Desmoid Tumors/Aggressive Fibromatosis | Phase 2 Interventional | National Institutes of Health Clinical Center (CC) | ||
NCT03785964 | Nirogacestat for Adults With Desmoid Tumor/Aggressive Fibromatosis (DT/AF) | Phase 3 Interventional | SpringWorks Therapeutics, Inc. | 4-5 | |
NCT05348356 | Nirogacestat in Ovarian Granulosa Cell Tumors | Phase 2 Interventional | SpringWorks Therapeutics, Inc. |