Nirogacestat 100mg tablets
Requires a prescription from a doctor or prescriber
Nirogacestat is a small-molecule gamma-secretase inhibitor that was investigated as a potential treatment for desmoid tumors.
Safety information for pregnancy and breastfeeding
Pregnancy
Due to the high level of protein binding, nirogacestat is not expected to be dialyzable.[L48857]
In a 6-month carcinogenicity study, transgenic rasH2 mice received up to 100 mg/kg/day of oral nirogacestat, resulting in mean exposure levels (AUC) less than those in humans at the recommended dose of 150 mg twice daily.
Always consult your doctor or midwife before taking any medicine during pregnancy or while breastfeeding. Source: DrugBank (CC BY-NC 4.0).
Official documents, adverse reaction reporting, and safety monitoring
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Safety monitoring data
Yellow Card reports
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Submit a Yellow Card report to the MHRA
Data from the MHRA Yellow Card scheme. A reported reaction does not necessarily mean the medicine caused it. Contains public sector information licensed under the Open Government Licence v3.0.
EudraVigilance
The European Medicines Agency (EMA) collects suspected adverse reaction reports from across the EU/EEA through the EudraVigilance system. Search for safety data on this medicine.
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Suspected adverse reactions reported for Nirogacestat
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EudraVigilance data is published by the European Medicines Agency (EMA). A suspected adverse reaction is not necessarily caused by the medicine.
1 branded products available
MHRA licensed products
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Ogsiveo 100mg tablets
Therapeutically similar medicines
Similarity is based on WHO Anatomical Therapeutic Chemical (ATC) classification and on a factual NHS dm+d therapeutic-grouping code prefix. Source data: NHS dm+d via TRUD (OGL v3.0), WHO ATC/DDD Index.
NHS prescribing volume and spending trends
Check stock at pharmacies and supply information
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Search for this medicine at major UK pharmacy chains. These links open the retailer's own website — results depend on their current online catalogue.
Supply & safety information
Official UK regulator monitoring and safety alerts
Pharmacy links redirect to the retailer's own search and do not represent real-time stock levels. Shortage and safety information sourced from MHRA drug safety updates (gov.uk, Crown Copyright under OGL v3.0).
Codes for healthcare professionals and prescribing systems
These codes are used by healthcare IT systems and prescribers to identify this medicine.
NHS UK identifiers
Browse tools
SNOMED CT and dm+d codes from NHS TRUD (Technology Reference data Update Distribution), licensed under the Open Government Licence v3.0. ATC codes from the WHO Collaborating Centre for Drug Statistics Methodology (whocc.no).
Active and completed clinical studies from ClinicalTrials.gov
Source: ClinicalTrials.gov, a database of the U.S. National Library of Medicine (NLM), National Institutes of Health (NIH). Data accessed via ClinicalTrials.gov API v2. Trial information is provided for research purposes and does not constitute medical advice.
Pharmacology and chemical data from DrugBank
Key facts
Drug status
Approved
Major interactions
None known
Half-life
Not available
Mechanism
Nirogacestat is a gamma secretase inhibitor that blocks proteolytic activation of the Notch receptor.
Food interactions
3 warnings
Human targets
6 targets
Data: DrugBank · CC BY-NC 4.0
Pharmacokinetics at a glance
Absorption
6 days
Half-life
[L48857]
Protein binding
99.6%
[L48857]
Volume of distribution
[L48857]
Metabolism
85%
[L48857]
…
Elimination
38%
Clearance
[L48857]
Pharmacokinetic data: DrugBank · CC BY-NC 4.0
Nirogacestat was approved under the brand name OGSIVEO on November 27, 2023, by the FDA for the treatment of adult patients with progressing desmoid tumors who require systemic treatment. It was previously granted breakthrough therapy, fast track, and orphan drug designations for the treatment of desmoid tumors, and the final approval was based on positive results obtained in the Phase 3 DeFi trial, where a confirmed objective response rate was observed to be 41% compared to 8% with the placebo.[L49036]
[L48857]
Known interactions with other medicines. Always consult a healthcare professional.
Showing 50 of 905 interactions
Advise pregnant women of the potential risk to a fetus.
[L48857]
Due to the high level of protein binding, nirogacestat is not expected to be dialyzable.
[L48857]
In a 6-month carcinogenicity study, transgenic rasH2 mice received up to 100 mg/kg/day of oral nirogacestat, resulting in mean exposure levels (AUC) less than those in humans at the recommended dose of 150 mg twice daily. No statistically significant neoplastic findings occurred. The carcinogenic potential of nirogacestat in rats has not been assessed.
[L48857]
Nirogacestat was not mutagenic in a bacterial reverse mutation (Ames) assay and was not clastogenic in an in vitro chromosome aberration assay in human lymphocytes or in vivo rat bone marrow micronucleus study.
[L48857]
Nirogacestat resulted in reduced fertility when administered to male and female rats at doses ≥ 5 mg/kg/day (approximately 0.16 times the recommended dose of 150 mg twice daily based on body surface area (BSA), and a lack of fertility when administered to male and female rats at doses ≥ 40 mg/kg/day (approximately 1.3 times the recommended dose of 150 mg twice daily based on BSA).
Adverse findings in rats included ovarian atrophy, reduced testes weights, and decreased sperm concentration and motility.
[L48857]
At the recommended dosage, a mean increase in the QTc interval > 20 ms was not observed.[L48857]
How the body processes this drug — absorption, distribution, metabolism, and elimination
[L48857]
[L48857]
[L48857]
[L48857]
[L48857]
[L48857]
[L48857]
Proteins and enzymes this drug interacts with in the body
PMID:10206644 PMID:10545183 PMID:10593990 PMID:10811883 PMID:10899933 PMID:12679784 PMID:12740439 PMID:15274632 PMID:20460383 PMID:25043039 PMID:26280335 PMID:28269784 PMID:30598546 PMID:30630874
Requires the presence of the other members of the gamma-secretase complex for protease activity .
PMID:15274632 PMID:25043039 PMID:26280335 PMID:30598546 PMID:30630874
Plays a role in Notch and Wnt signaling cascades and regulation of downstream processes via its role in processing key regulatory proteins, and by regulating cytosolic CTNNB1 levels .
PMID:10593990 PMID:10811883 PMID:10899933 PMID:9738936
Stimulates cell-cell adhesion via its interaction with CDH1; this stabilizes the complexes between CDH1 (E-cadherin) and its interaction partners CTNNB1 (beta-catenin), CTNND1 and JUP (gamma-catenin) .
PMID:11953314
Under conditions of apoptosis or calcium influx, cleaves CDH1 .
PMID:11953314
This promotes the disassembly of the complexes between CDH1 and CTNND1, JUP and CTNNB1, increases the pool of cytoplasmic CTNNB1, and thereby negatively regulates Wnt signaling .
PMID:11953314 PMID:9738936
Required for normal embryonic brain and skeleton development, and for normal angiogenesis (By similarity). Mediates the proteolytic cleavage of EphB2/CTF1 into EphB2/CTF2 .
PMID:17428795 PMID:28269784
The holoprotein functions as a calcium-leak channel that allows the passive movement of calcium from endoplasmic reticulum to cytosol and is therefore involved in calcium homeostasis .
PMID:16959576 PMID:25394380
Involved in the regulation of neurite outgrowth .
PMID:15004326 PMID:20460383
Is a regulator of presynaptic facilitation, spike transmission and synaptic vesicles replenishment in a process that depends on gamma-secretase activity. It acts through the control of SYT7 presynaptic expression (By similarity)
May function in the cytoplasmic partitioning of proteins. The holoprotein functions as a calcium-leak channel that allows the passive movement of calcium from endoplasmic reticulum to cytosol and is involved in calcium homeostasis .
PMID:16959576
Is a regulator of mitochondrion-endoplasmic reticulum membrane tethering and modulates calcium ions shuttling between ER and mitochondria PMID:21285369
PMID:10993067 PMID:12679784 PMID:25043039 PMID:26280335 PMID:30598546 PMID:30630874
The gamma-secretase complex plays a role in Notch and Wnt signaling cascades and regulation of downstream processes via its role in processing key regulatory proteins, and by regulating cytosolic CTNNB1 levels
PMID:12522139 PMID:12679784 PMID:12740439 PMID:12763021 PMID:24941111 PMID:30598546 PMID:30630874
The gamma-secretase complex plays a role in Notch and Wnt signaling cascades and regulation of downstream processes via its role in processing key regulatory proteins, and by regulating cytosolic CTNNB1 levels (Probable). PSENEN modulates both endoproteolysis of presenilin and gamma-secretase activity PMID:12522139 PMID:12679784 PMID:12740439 PMID:12763021 PMID:24941111
Enzymes involved in drug metabolism — important for understanding drug interactions
Proteins that transport this drug across cell membranes
PMID:2897240 PMID:35970996 PMID:8898203 PMID:9038218 PMID:35507548
Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of phosphatidylcholine, phosphatidylethanolamine, beta-D-glucosylceramides and sphingomyelins .
PMID:8898203
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells PMID:2897240 PMID:35970996 PMID:9038218
Proteins that carry this drug through the body
PMID:19021548
Major calcium and magnesium transporter in plasma, binds approximately 45% of circulating calcium and magnesium in plasma (By similarity).
Potentially has more than two calcium-binding sites and might additionally bind calcium in a non-specific manner (By similarity). The shared binding site between zinc and calcium at residue Asp-273 suggests a crosstalk between zinc and calcium transport in the blood (By similarity). The rank order of affinity is zinc > calcium > magnesium (By similarity).
Binds to the bacterial siderophore enterobactin and inhibits enterobactin-mediated iron uptake of E.coli from ferric transferrin, and may thereby limit the utilization of iron and growth of enteric bacteria such as E.coli .
PMID:6234017
Does not prevent iron uptake by the bacterial siderophore aerobactin PMID:6234017
Appears to function in modulating the activity of the immune system during the acute-phase reaction
ATC L01XX81
Chemical identifiers
CAS, UNII, InChI Key and database cross-references
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Chemical identifiers
CAS, UNII, InChI Key and database cross-references
Linked compound data from DrugBank Open Data (CC BY-NC 4.0)
Nirogacestat
Additional database identifiers
ChemSpider
26232306
BindingDB
50458159
PDB
O6U
ZINC
ZINC000038217837
HUGO Gene Nomenclature Committee (HGNC)
HGNC:9508
GeneCards
PSEN1
Guide to Pharmacology
2402
UniProt Accession
PSN1_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:9509
GeneCards
PSEN2
UniProt Accession
PSN2_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:17091
GeneCards
NCSTN
UniProt Accession
NICA_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:30100
GenAtlas
PSENEN
GeneCards
PSENEN
GenBank Gene Database
AF220053
UniProt Accession
PEN2_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:24080
GeneCards
APH1B
UniProt Accession
APH1B_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:29509
GenAtlas
APH1A
GeneCards
APH1A
GenBank Gene Database
AF508787
UniProt Accession
APH1A_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:2615
GeneCards
CYP2B6
GenBank Gene Database
M29874
GenBank Protein Database
181296
Guide to Pharmacology
1324
UniProt Accession
CP2B6_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:2625
GenAtlas
CYP2D6
GeneCards
CYP2D6
GenBank Gene Database
M20403
GenBank Protein Database
181350
Guide to Pharmacology
1329
UniProt Accession
CP2D6_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:2623
GenAtlas
CYP2C9
GeneCards
CYP2C9
GenBank Gene Database
AY341248
Guide to Pharmacology
1326
UniProt Accession
CP2C9_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:2621
GeneCards
CYP2C19
GenBank Gene Database
M61854
GenBank Protein Database
181344
Guide to Pharmacology
1328
UniProt Accession
CP2CJ_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:2637
GenAtlas
CYP3A4
GeneCards
CYP3A4
GenBank Gene Database
M18907
Guide to Pharmacology
1337
UniProt Accession
CP3A4_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:2622
GenAtlas
CYP2C8
GeneCards
CYP2C8
GenBank Gene Database
M17397
Guide to Pharmacology
1325
UniProt Accession
CP2C8_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:399
GenAtlas
ALB
GeneCards
ALB
GenBank Gene Database
V00494
GenBank Protein Database
28590
UniProt Accession
ALBU_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:8498
GenAtlas
ORM1
GeneCards
ORM1
GenBank Gene Database
X02544
GenBank Protein Database
757907
UniProt Accession
A1AG1_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:8499
GeneCards
ORM2
GenBank Gene Database
BC015964
GenBank Protein Database
16359000
UniProt Accession
A1AG2_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:40
GenAtlas
ABCB1
GeneCards
ABCB1
GenBank Gene Database
M14758
GenBank Protein Database
307180
Guide to Pharmacology
768
UniProt Accession
MDR1_HUMAN
DrugBank citations
If you use DrugBank data in your research, please cite:
- DrugBank 6.02024Recommended citationKnox C., Wilson M., Klinger C.M., et alDrugBank 6.0: the DrugBank Knowledgebase for 2024Nucleic Acids Res. 2024 Jan 552(D1):D1265-D1275
- DrugBank 5.02018Wishart D.S., Feunang Y.D., Guo A.C., et alDrugBank 5.0: a major update to the DrugBank database for 2018Nucleic Acids Res. 2017 Nov 846(D1):D1074-D1082
- DrugBank 4.02014Law V., Knox C., Djoumbou Y., et alDrugBank 4.0: shedding new light on drug metabolismNucleic Acids Res. 2014 Jan 142(1):D1091-7
- DrugBank 3.02011Knox C., Law V., Jewison T., et alDrugBank 3.0: a comprehensive resource for 'omics' research on drugsNucleic Acids Res. 2011 Jan39(Database issue):D1035-41
- DrugBank 2.02008Wishart D.S., Knox C., Guo A.C., et alDrugBank: a knowledgebase for drugs, drug actions and drug targets.Nucleic Acids Research2008 Jan36(Database issue):D901-6
- DrugBank 1.02006Wishart D.S., Knox C., Guo A.C., et alDrugBank: a comprehensive resource for in silico drug discovery and exploration.Nucleic Acids Research2006 Jan 134(Database issue):D668-72
Structured knowledge from the free knowledge base
Linked open data from Wikidata (Q27088329), a free and open knowledge base operated by the Wikimedia Foundation. Data is available under the Creative Commons CC0 1.0 Public Domain Dedication.