PF-06447475 Struktur

PF-06447475

Bezeichnung:PF-06447475

CAS-Nr1527473-33-1

Englisch Name:PF-06447475

CBNumberCB52735532

SummenformelC17H15N5O

Molgewicht305.33

MOL-Datei1527473-33-1.mol

PF-06447475 physikalisch-chemischer Eigenschaften

Schmelzpunkt	>223°C (dec.)
Dichte	1.40±0.1 g/cm3(Predicted)
storage temp.	room temp
Löslichkeit	DMSO: soluble10mg/mL, clear
pka	12.96±0.50(Predicted)
Aggregatzustand	powder
Farbe	white to beige

Sicherheit

Kennzeichnung gefährlicher	T
R-Sätze:	25
S-Sätze:	45
RIDADR	UN 2811 6.1 / PGIII

Gefahreninformationscode (GHS)

PF-06447475 Chemische Eigenschaften,Einsatz,Produktion Methoden

Verwenden
PF 06447475 is a highly potent LRRK2 kinase inhibitor. Highly selective, and mobile, it is used in the treatment of Parkinson’s disease which has been linked to Leucine rich repeat kinase 2 (LRRK2) enzymes.
Enzyminhibitor
This potent, brain penetrant and selective LRRK2 inhibitor (FW = 305.44 g/mol; CAS 1527473-33-1), also named 3-[4-(4-morpholinyl)-7Hpyrrolo[2,3-d]pyrimidin-5-yl]benzonitrile, targets Leucine-Rich Repeat Kinase 2, IC50 = 3 nM, (encoded by the PARK8 gene), which phosphorylates Akt1 (Ser-473), suggesting that Akt1 is a convincing candidate for the physiological substrate of LRRK2. Diseaseassociated mutations forms of LRRK2 (including Arg-1441-Cys, Gly-2019- Ser, and Ile-2020-Thr) exhibit reduced interaction with, and phosphorylation of, Akt1, a finding that suggests a possible mechanism for the neurodegeneration caused by LRRK2 mutations. Therapeutic approaches to slow or block the progression of Parkinson disease (PD) do not exist. Given that genetic and biochemical studies implicate α-synuclein and leucine-rich repeat kinase 2 (LRRK2) in late-onset PD. In wild-type rats as well as transgenic [Gly-2019-Ser]-LRRK2 rats that were injected intracranially with adeno-associated viral vectors expressing human α- synuclein in the substantia nigra, those expressing [Gly-2019-Ser]-LRRK2 show exacerbated dopaminergic neurodegeneration and inflammation in response to the overexpression of α-synuclein. Both neurodegeneration and neuroinflammation associated with [Gly-2019-Ser]-LRRK2 expression were mitigated by PF-06447475, which provided neuroprotection in wildtype rats. There are no adverse pathological indications in the lung, kidney, or liver of rats treated with PF-06447475. Pharmacological inhibition of LRRK2 is well tolerated for a 4-week period of time in rats and can counteract dopaminergic neurodegeneration caused by acute α-synuclein overexpression

PF-06447475 Upstream-Materialien And Downstream Produkte

PF-06447475 Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

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