N-((2R)-2,3-Dihydroxypropoxy)-3,4-difluoro-2-((2-fluoro-4-iodophenyl)amino)benzamide
Grundinformationen
- CAS
391210-10-9- Standard-SMILES
O=C(NOC[C@H](O)CO)c1ccc(F)c(F)c1Nc1ccc(I)cc1F- InChIKey
SUDAHWBOROXANE-SECBINFHSA-N- Summenformel
- C16H14F3IN2O4
- Durchschnittliche Molmasse
- 482,19 g/mol
- Monoisotopische Masse
- 481,99503959
Überblick
PD 0325901 is a hydroxamic acid ester that is benzhydroxamic acid (N-hydroxybenzamide) in which the hydroxamic acid group has been converted to the corresponding 2,3-dihydroxypropyl ester and in which the benzene ring has been substituted at position 2 by a (2-fluoro-4-iodophenyl)amino group and at positions 3 and 4 by fluorines (the R enantiomer). It has a role as an antineoplastic agent and an EC 2.7.12.2 (mitogen-activated protein kinase kinase) inhibitor. It is a member of propane-1,2-diols, an organoiodine compound, a difluorobenzene, a secondary amino compound, a hydroxamic acid ester and a member of monofluorobenzenes.
Namen und Bezeichner
- Bevorzugter Name
- N-((2R)-2,3-Dihydroxypropoxy)-3,4-difluoro-2-((2-fluoro-4-iodophenyl)amino)benzamide
- IUPAC
- N-[(2R)-2,3-dihydroxypropoxy]-3,4-difluoro-2-(2-fluoro-4-iodoanilino)benzamide
- Englischer Name
- PD 0325901
- Summenformel
- C16H14F3IN2O4
- Molmasse
- 482.19
Namen und Synonyme
391210-10-9MirdametinibPD0325901PD 0325901PD-0325901N-[(2R)-2,3-dihydroxypropoxy]-3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]benzamideGOMEKLIPD 32590186K0J5AK6MDTXSID0044024DTXCID8024024CHEBI:88249
Weitere Namen anzeigen
Mirdametinib (PD0325901)N-[(2R)-2,3-DIHYDROXYPROPOXY]-3,4-DIFLUORO-2-[(2-FLUORO-4-IODOPHENYL)AMINO]-BENZAMIDECS-52PD 032590PD-0235901PD0325901, >=98%MEK1/2 Inhibitor III
Pd 901PD-901Benzamide, N-[(2R)-2,3-dihydroxypropoxy]-3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]-PD-03525901Benzamide, N-((2R)-2,3-dihydroxypropoxy)-3,4-difluoro-2-((2-fluoro-4-iodophenyl)amino)-N-((2R)-2,3-Dihydroxypropoxy)-3,4-difluoro-2-((2-fluoro-4-iodophenyl)amino)benzamidePD325901RefChem:818905
Datenbank-Bezeichner
- CAS
391210-10-9- PubChem CID
- 9826528
- DTXSID
Eigenschaften
Berechnete Struktureigenschaften
- XLogP
- 3
- Polarare Oberfläche (TPSA)
- 90,8 Ų
- H-Brücken-Donoren
- 4
- H-Brücken-Akzeptoren
- 8
- Frei drehbare Bindungen
- 7
- Schwere Atome
- 26
- Formalladung
- 0
- Komplexität
- 465
Experimentelle und physikochemische Eigenschaften
DrugsPharmaceuticals -> Listed in ZINC15
Human Drugs
Breast Feeding; Lactation; Milk, Human; Antineoplastic Agents; Enzyme Inhibitors; Protein Kinase Inhibitors; MEK inhibitors
FDA approved drugs -> Active ingredient
EMA approved medicines: Human medicine (Orphan designations)
FDA approved drugs -> Active ingredient
Dissociation Constants7.96
Physikochemische Eigenschaften
- Schmelzpunkt
- 112 · 112-114°C
- Dichte
- 1.817 · 1.817±0.06 g/cm3(Predicted)
- storage temp.
- 2 · 2-8°C
- Löslichkeit
- 20 mg/mL, · DMSO: soluble20mg/mL, clear
- Aggregatzustand
- White to off-white solid
- pka
- 13.45 · 13.45±0.20(Predicted)
- Farbe
- white to off-white
- Stabilität
- 1 year · Stable for 1 year from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20° for up to 3 months.
Sicherheit und Regulatorisches
Sicherheitsangaben dienen nur zur Orientierung und ersetzen weder das Sicherheitsdatenblatt (SDB) des Lieferanten noch geltende Vorschriften oder eine fachliche Bewertung.
GHS-Klassifizierung
GHS Classification
Danger
H301 (97.5%): Toxic if swallowed [Danger Acute toxicity, oral]
P260, P264, P270, P273, P301+P316, P319, P321, P330, P391, P405, and P501 (click each P-code to see the statement)
Aggregated GHS information provided per 40 reports by companies from 3 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.
Gefahrenhinweise
Hazard Classes and CategoriesAcute Tox. 3 (97.5%)
Toxikologische Informationen
Effects During Pregnancy and Lactation◉ Summary of Use during Lactation
Sicherheitsdaten
- wgk
- 3
- ridadr
- UN 2811 6.1 / PGIII
- hs_code
- 29242990
- risk_code
- 25-48-50
- hazard_code
- T,N
- safety_code
- 22-36/37/39-61
- hazard_class
- IRRITANT
- Speicherklasse
- 10 - Combustible liquids
Chemie und Industrie
Pharmakologische Informationen
ATC Code
L - Antineoplastic and immunomodulating agents
QL - Antineoplastic and immunomodulating agents
Protein BindingHuman plasma protein binding is greater than 99%.
PharmacodynamicsIn a mouse model of NF1, oral dosing of mirdametinib inhibited ERK phosphorylation and reduced neurofibroma tumour volume and proliferation.
Mechanism of Action
NF1 is caused by the loss-of-function variants in the _NF1_ tumour suppressor gene, which encodes neurofibromin: Neurofibromin loss in tumour cells leads to dysregulated Ras signalling with hyperactivation of downstream Ras effectors, including mitogen-activated protein kinase (MAPK, MEK) and its downstream effector extracellular signal–regulated protein kinase (ERK). As the MAPK pathway regulates cellular functions such as cellular growth and senescence, dysregulation of this pathway aberrant glioblastoma cell growth. Mirdametinib is a highly selective, non-competitive inhibitor of MEK1/2. In vitro, mirdametinib inhibited kinase activity of MEK1 and MEK2 and downstream phosphorylation of ERK.
Biological Half-LifeThe mean (%CV) terminal elimination half-life is 28 h (12%).
Metabolism/MetabolitesMetabolism involves glucuronidation and oxidation via UGT (primarily UGT1A6 and UGT2B7) and carboxylesterase enzymes.
FDA Pharmacological Classification
86K0J5AK6M
MIRDAMETINIB
Established Pharmacologic Class [EPC] - Kinase Inhibitor
Mechanisms of Action [MoA] - Mitogen-Activated Protein Kinase Kinase 1 Inhibitors
Mechanisms of Action [MoA] - Mitogen-Activated Protein Kinase Kinase 2 Inhibitors
Mirdametinib is a Kinase Inhibitor. The mechanism of action of mirdametinib is as a Mitogen-Activated Protein Kinase Kinase 1 Inhibitor and Mitogen-Activated Protein Kinase Kinase 2 Inhibitor.
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