KPT-9294 Struktur

KPT-9294

Bezeichnung:KPT-9294

CAS-Nr1643913-93-2

Englisch Name:KPT-9294

CBNumberCB72741566

SummenformelC35H29F3N4O3

Molgewicht610.62

MOL-Datei1643913-93-2.mol

KPT-9294 physikalisch-chemischer Eigenschaften

Siedepunkt	857.5±65.0 °C(Predicted)
Dichte	1.39±0.1 g/cm3(Predicted)
storage temp.	Store at -20°C
Löslichkeit	≥22.45 mg/mL in DMSO; insoluble in H2O; insoluble in EtOH
Aggregatzustand	solid
pka	12.96±0.46(Predicted)
Farbe	White to light yellow

Gefahreninformationscode (GHS)

KPT-9294 Chemische Eigenschaften,Einsatz,Produktion Methoden

Biologische Aktivität
kpt-9274 is a selective and orally bioavailable allosteric inhibitor of pak4 [1][2][3].p21 protein (cdc42/rac)-activated kinase 4 (pak4) is a serine/threonine-protein kinase and a member of the pak family of proteins which are rac1 and cdc42 effectors. pak4 is a mediator of filopodia formation and stabilizes β-catenin transcriptional activity, and is involved in disease progression for several solid tumors [1][2][3].kpt-9274 is a selective and orally bioavailable pak4 inhibitor. in mda-mb-468 cells, kpt-9274 showed anti-tumor activity with ic50 value of 0.12 μm. kpt-9274 reduced pak4 protein and the key downstream effectors of cell cycle (β-catenin, cyclin d1), cell migration (cofilin), autophagy (ampk) and apoptosis (caspase and parp cleavage) [1]. in rcc cells, kpt-9274 dose-dependently inhibited cell viability [2]. in aml cell lines, kpt-9274 (1 nm-10 μm) inhibited cell proliferation in a dose-and time- dependent way and reduced protein and mrna expression of pak4 [3].in mice inoculated with mda-mb-231 or mda-mb-468 cells, kpt-9274 were given orally once daily (5 or 7 days/week) without major toxicity. kpt-9274 induced a maximum tgi of ~55% and ~70% in mda-mb-231 and mda-mb-468 mice, respectively [1]. in subcutaneous xenograft mouse models, kpt-9274 inhibited rcc growth [2]. in human aml leukemia xenograft model, kpt-9274 (150 mg/kg) significantly inhibited tumor growth, prevented invasion of mv4-11 cells, and improved overall survival [3].
Einzelnachweise
[1]. senapedis w, george r, mccauley d, et al. preclinical evaluation of novel pak4 allosteric modulators against triple negative breast cancer.
[2]. aboud oa, senapedis w, landesman y, et al. inhibition of pak4 attenuates renal cell carcinoma (rcc) growth.
[3]. mitchell s, orwick s, cannon m, et al. in vitro and in vivo anti-leukemic effects of kpt-9274, a reported pak4 allosteric modulator, in acute myeloid leukemia: promising results justifying further development in this disease. 57th annual meeting & exposition. orlando, fl december 5-8, 2015.

KPT-9294 Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

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