PF-3758309

Bezeichnung:PF-3758309

CAS-Nr898044-15-0

Englisch Name:PF-3758309

CBNumberCB32624276

SummenformelC25H30N8OS

Molgewicht490.62

MOL-Datei898044-15-0.mol

PF-3758309 physikalisch-chemischer Eigenschaften

Dichte	1.325±0.06 g/cm3(Predicted)
storage temp.	-20C
Löslichkeit	≥24.53 mg/mL in DMSO; insoluble in H2O; ≥101.4 mg/mL in EtOH with gentle warming and ultrasonic
Aggregatzustand	Yellowish-white powder
pka	12.82±0.40(Predicted)
Farbe	White to light yellow

Gefahreninformationscode (GHS)

PF-3758309 Chemische Eigenschaften,Einsatz,Produktion Methoden

Verwenden
PF-3758309 is a pyrrolopyrazole inhibitor of PAK4 (p21-activated kinase). It is used in biological studies for targeting Rho GTPase signaling for cancer therapy.
Definition
ChEBI: N-[(1S)-2-(dimethylamino)-1-phenylethyl]-6,6-dimethyl-3-[(2-methyl-4-thieno[3,2-d]pyrimidinyl)amino]-1,4-dihydropyrrolo[3,4-c]pyrazole-5-carboxamide is an organic heterobicyclic compound, an organosulfur heterocyclic compound and an organonitrogen heterocyclic compound.
Biologische Aktivität
pf-3758309 is an inhbitor of pak4 with ic50 of 1.3 nm [1].p21-activated kinases (paks) are the family of serine/theronine kinases, which play important role in linking rho gtpase to cytoskeleton reorganization and nuclear signaling. pak4 is a member of paks family, specifically responsive for interacting with gtp bound form of cdc42 and jnk family. pak4 is involved in filopodia formation and may play a role in the reorganization of the actin cytoskeleton.biochemical study had identified that pf-3758309 was an atp-competitive inhibitor of pak4, which inhibited the kinase activity [1]. when pak4 was screened with a panel of tumor cell lines, it was found pf-3758309 inhibited the phosphorylation of pak4 substrate gef-h1, and also the pak4-induced anchorage-independent cell growth, with ic50 value of 1.3 nm and 4.7 ±3 nm respectively [1]. when pf-3758309 was screened with a panel of paks related kinases, it exhibited good potency and specificity for pak4 [1]. cell analysis conﬁrmed that pf-3758309 modulates pak4-dependent signaling nodes and identiﬁes unexpected links to additional p53pathways [1].
in vivo
activity of pf-3758309 was examined in a panel of human xenograft model, including hct116 and a549 model. twice daily oral administration of pf-3758309 (7.5-30 mg/kg bid) for 9-18 days resulted in significant inhibition of tumor growth in all the models. the tumor growth was shown to be caused by pak-dependent pathways in hct116 and a549 model. additionally, pf-3758309 was shown to regulate pak-associated cell proliferation and survival in certain models. therefore, pf-3758309 exhibited inhibitory activity on pak4 [1].
Einzelnachweise
[1] murray b w et al. , small-molecule p21-activated kinase inhibitor pf-3758309 is a potent inhibitor of oncogenic signaling and tumor growth. proc natl acad sci usa. 2010, 107(20): 9446-9451.

PF-3758309 Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

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