AP26113

Bezeichnung:AP26113

CAS-Nr1197958-12-5

Englisch Name:AP26113

CBNumberCB12642542

SummenformelC26H34ClN6O2P

Molgewicht529.01

MOL-Datei1197958-12-5.mol

AP26113 physikalisch-chemischer Eigenschaften

Siedepunkt	737.6±70.0 °C(Predicted)
Dichte	1.29±0.1 g/cm3(Predicted)
storage temp.	Store at -20°C
Löslichkeit	≥26.45 mg/mL in DMSO; insoluble in H2O; ≥55.9 mg/mL in EtOH
Aggregatzustand	solid
pka	9.27±0.20(Predicted)
Farbe	White to off-white
CAS Datenbank	1197958-12-5

Gefahreninformationscode (GHS)

AP26113 Chemische Eigenschaften,Einsatz,Produktion Methoden

Verwenden
AP 26113 is a potent anaplastic lymphoma kinase (ALK) inhibitor. It is also an epidermal growth factor (EGFR) receptor tyrosine kinase inhibitor used for treatment of lung cancer.
Biologische Aktivität
ap26113 is a novel, synthetic, orally available small-molecule inhibitor of anaplastic lymphoma kinase (alk), which is a receptor tyrosine kinase in the insulin receptor superfamily, with half maximal inhibitory concentration ic50 ranging from 5 nmol/l to 11 nmol/l. ap26113 is also capable of inhibiting the alk tyrosine kinase gatekeeper mutation l1196m (ic50: 15 nmol/l to 45 nmol/l), mutant epidermal growth factor receptor (egfr) containing the gatekeeper t790m mutation and c-ros oncogene 1 (ros1). moreover, ap26113 has been found to be active against h3122 cells (both sensitive and resistant) and ba/f3 cells harboring native or mutant eml4-alk (ic50: 10 nm and 24 nm respectively).
Enzyminhibitor
This potent ALK inhibitor (FW = 529.02 g/mol; CAS 1197958-12-5; Solubility: 45 mg/mL DMSO; <1 mg/mL H2O), also named 5-chloro-N2-[4-[4-(dimethylamino)-1-piperidinyl]-2-methoxyphenyl]-N4-[2-(dimethyl- phosphinyl)phenyl]-2,4-pyrimidinediamine, inhibits wild type Lymphoma Kinase, or ALK (Ki = 0.62 nM) and overcomes crizotinib resistance in non- small cell lung cancers harboring the fusion oncogene EML4-ALK. Cells often develop the L1196M gatekeeper mutation within the kinase domain, a changes that renders them resistant to crizotinib, even at higher drug doses (1 μM). AP26113 is highly active against these resistant cancer cells, both in vitro and in vivo.
target
ALK
Einzelnachweise
[1]solomon b, wilner kd, shaw at. current status of targeted therapy for anaplastic lymphoma kinase-rearranged non-small cell lung cancer. clin pharmacol ther. 2014 jan;95(1):15-23. doi: 10.1038/clpt.2013.200. epub 2013 oct 3.
[2]katayama r1, khan tm, benes c, lifshits e, ebi h, rivera vm, shakespeare wc, iafrate aj, engelman ja, shaw at. therapeutic strategies to overcome crizotinib resistance in non-small cell lung cancers harboring the fusion oncogene eml4-alk. proc natl acad sci u s a. 2011 may 3;108(18):7535-40. doi: 10.1073/pnas.1019559108. epub 2011 apr 18.

AP26113 Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

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