Mirdametinib 1mg dispersible tablets sugar free
Requires a prescription from a doctor or prescriber
Mirdametinib is a mitogen-activated protein kinase (MAP2K, MEK, MAPKK) inhibitor.
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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.
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Suspected adverse reactions reported for Mirdametinib
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Ezmekly 1mg dispersible 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
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Supply & safety information
Official UK regulator monitoring and safety alerts
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Codes for healthcare professionals and prescribing systems
These codes are used by healthcare IT systems and prescribers to identify this medicine.
NHS UK identifiers
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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
28 h
Mechanism
NF1 is caused by the loss-of-function variants in the NF1 tumour suppressor gene…
Food interactions
1 warning
Human targets
2 targets
Data: DrugBank · CC BY-NC 4.0
Pharmacokinetics at a glance
Absorption
52%
Half-life
28 h
[L52265]
Protein binding
99%
[L52265]
Volume of distribution
255 L
[L52265]
Mirdametinib penetrates the central nervous system.
[A265065]
Metabolism
[L52265]
Elimination
68%
Clearance
6.3 L/h
[L52265]
Pharmacokinetic data: DrugBank · CC BY-NC 4.0
NF1 is an autosomal-dominant genetic condition caused by loss-of-function variants in the NF1 tumour suppressor gene,[A265065][A265070] leading to neurofibromin dysfunction and aberrant activation of the mitogen-activated protein kinase (MAPK) pathway.[A265065] Mirdametinib selectively and potently inhibits the MEK1/2 enzymes.[A265065]
[L52265]
Known interactions with other medicines. Always consult a healthcare professional.
Showing 38 of 38 interactions
Mirdametinib is a highly selective, non-competitive inhibitor of MEK1/2.[A265070] In vitro, mirdametinib inhibited kinase activity of MEK1 and MEK2 and downstream phosphorylation of ERK.[L52265]
How the body processes this drug — absorption, distribution, metabolism, and elimination
The mean accumulation ratio is 1.1 to 1.9.
[L52265]
The median (min, max) Tmax is 0.8 (0.4-3) hours post-dose in tablets and 1.1 (0-4) hours post-dose in capsules. There is no data on the absolute bioavailability of mirdametinib. The effect of a high-fat, high-calorie meal on drug absorption was assessed using the geometric mean ratio (GMR%) and the 90% confidence interval (CI): The GMR was 57% (54%, 61%) for Cmax and 93% (90%, 96%) for AUCinf, indicating that a high-fat, high-calorie meal reduces Cmax but has negligible effects on drug exposure.
[L52265]
[L52265]
[L52265]
[L52265]
Mirdametinib penetrates the central nervous system.
[A265065]
[L52265]
[L52265]
[L52265]
Proteins and enzymes this drug interacts with in the body
Both MAP2K1/MEK1 and MAP2K2/MEK2 function specifically in the MAPK/ERK cascade, and catalyze the concomitant phosphorylation of a threonine and a tyrosine residue in a Thr-Glu-Tyr sequence located in the extracellular signal-regulated kinases MAPK3/ERK1 and MAPK1/ERK2, leading to their activation and further transduction of the signal within the MAPK/ERK cascade. Activates BRAF in a KSR1 or KSR2-dependent manner; by binding to KSR1 or KSR2 releases the inhibitory intramolecular interaction between KSR1 or KSR2 protein kinase and N-terminal domains which promotes KSR1 or KSR2-BRAF dimerization and BRAF activation .
PMID:29433126
Depending on the cellular context, this pathway mediates diverse biological functions such as cell growth, adhesion, survival and differentiation, predominantly through the regulation of transcription, metabolism and cytoskeletal rearrangements. One target of the MAPK/ERK cascade is peroxisome proliferator-activated receptor gamma (PPARG), a nuclear receptor that promotes differentiation and apoptosis.
MAP2K1/MEK1 has been shown to export PPARG from the nucleus. The MAPK/ERK cascade is also involved in the regulation of endosomal dynamics, including lysosome processing and endosome cycling through the perinuclear recycling compartment (PNRC), as well as in the fragmentation of the Golgi apparatus during mitosis
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
PMID:11306452 PMID:12958161 PMID:19506252 PMID:20705604 PMID:28554189 PMID:30405239 PMID:31003562
Involved in porphyrin homeostasis, mediating the export of protoporphyrin IX (PPIX) from both mitochondria to cytosol and cytosol to extracellular space, it also functions in the cellular export of heme .
PMID:20705604 PMID:23189181
Also mediates the efflux of sphingosine-1-P from cells .
PMID:20110355
Acts as a urate exporter functioning in both renal and extrarenal urate excretion .
PMID:19506252 PMID:20368174 PMID:22132962 PMID:31003562 PMID:36749388
In kidney, it also functions as a physiological exporter of the uremic toxin indoxyl sulfate (By similarity). Also involved in the excretion of steroids like estrone 3-sulfate/E1S, 3beta-sulfooxy-androst-5-en-17-one/DHEAS, and other sulfate conjugates .
PMID:12682043 PMID:28554189 PMID:30405239
Mediates the secretion of the riboflavin and biotin vitamins into milk (By similarity). Extrudes pheophorbide a, a phototoxic porphyrin catabolite of chlorophyll, reducing its bioavailability (By similarity).
Plays an important role in the exclusion of xenobiotics from the brain (Probable). It confers to cells a resistance to multiple drugs and other xenobiotics including mitoxantrone, pheophorbide, camptothecin, methotrexate, azidothymidine, and the anthracyclines daunorubicin and doxorubicin, through the control of their efflux .
PMID:11306452 PMID:12477054 PMID:15670731 PMID:18056989 PMID:31254042
In placenta, it limits the penetration of drugs from the maternal plasma into the fetus (By similarity). May play a role in early stem cell self-renewal by blocking differentiation (By similarity).
In inflammatory macrophages, exports itaconate from the cytosol to the extracellular compartment and limits the activation of TFEB-dependent lysosome biogenesis involved in antibacterial innate immune response
ATC L01EE05
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)
Mirdametinib
Additional database identifiers
ChemSpider
8002271
BindingDB
104963
PDB
4BM
ZINC
ZINC000003938683
HUGO Gene Nomenclature Committee (HGNC)
HGNC:6840
GenAtlas
MAP2K1
GeneCards
MAP2K1
GenBank Gene Database
L05624
GenBank Protein Database
188569
Guide to Pharmacology
2062
UniProt Accession
MP2K1_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:6842
GeneCards
MAP2K2
Guide to Pharmacology
2063
UniProt Accession
MP2K2_HUMAN
UniProt Accession
Q6LAP9_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:12538
GeneCards
UGT1A6
UniProt Accession
UD16_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:12554
GeneCards
UGT2B7
GenBank Gene Database
J05428
GenBank Protein Database
340080
UniProt Accession
UD2B7_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
HUGO Gene Nomenclature Committee (HGNC)
HGNC:74
GenAtlas
ABCG2
GeneCards
ABCG2
GenBank Gene Database
AF103796
GenBank Protein Database
4185796
Guide to Pharmacology
792
UniProt Accession
ABCG2_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 (Q27088255), a free and open knowledge base operated by the Wikimedia Foundation. Data is available under the Creative Commons CC0 1.0 Public Domain Dedication.