| Identification | Back Directory | [Name]
PFE-360 | [CAS]
1527475-61-1 | [Synonyms]
PFE-360
PF-06685360
1H-Pyrrole-2-carbonitrile, 1-methyl-4-[4-(4-morpholinyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl]- | [Molecular Formula]
C16H16N6O | [MOL File]
1527475-61-1.mol | [Molecular Weight]
308.34 |
| Hazard Information | Back Directory | [Description]
PFE-360 (PF-06685360) is a poten and elective inhibitor of LRRK2 kinase. | [Uses]
PFE-360 (PF-06685360) is a potent, selective, brain penetrated and orally active leucine-rich repeat kinase 2 (LRRK2) inhibitor with a mean IC50 of 2.3 nM in vivo[1][2]. | [in vitro]
PFE-360 (4 mg/kg and 7.5 mg/kg, orally, BID, 10-12 weeks) treatment potently decreases the LRRK2-pSer935/total LRRK2 ratio, with no significant adverse effects.
animal Model: Female Sprague Dawley rats (NTac:SD) weighed 225-250 g.
Dosage: 4 mg/kg and 7.5 mg/kg (pharmacokinetics and pharmacodynamics).
Administration: Orally BID for 10-12 weeks.
Result: The LRRK2-pSer935/total LRRK2 ratio was significantly decreased at both 1 h and 12 h after dosing.
The terminal bodyweights exhibited no significant changes. | [in vivo]
PFE-360 (4 mg/kg and 7.5 mg/kg, orally, BID, 10-12 weeks) treatment potently decreases the LRRK2-pSer935/total LRRK2 ratio, with no significant adverse effects[1]. | Animal Model: | Female Sprague Dawley rats (NTac:SD) weighed 225-250 g[3]. | | Dosage: | 4 mg/kg and 7.5 mg/kg (pharmacokinetics and pharmacodynamics). | | Administration: | Orally BID for 10-12 weeks. | | Result: | The LRRK2-pSer935/total LRRK2 ratio was significantly decreased at both 1 h and 12 h after dosing.
The terminal bodyweights exhibited no significant changes.
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| [storage]
Store at -20°C | [References]
[1] Marco A.S. Baptista, et al. LRRK2 Kinase Inhibitors of Different Structural Classes Induce Abnormal Accumulation of Lamellar Bodies in Type II Pneumocytes in Non-Human Primates but are Reversible and Without Pulmonary Functional Consequences.
[2] Andersen MA, et al. Parkinson's disease-like burst firing activity in subthalamic nucleus induced by AAV-α-synuclein is normalized by LRRK2 modulation. Neurobiol Dis. 2018 Aug;116:13-27. DOI:10.1016/j.nbd.2018.04.011
[3] Andersen MA, et al. PFE-360-induced LRRK2 inhibition induces reversible, non-adverse renal changes in rats. Toxicology. 2018 Feb 15;395:15-22. DOI:10.1016/j.tox.2018.01.003 |
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