PFE-360 (PF-06685360) is a potent, selective, brain penetrated and orally active leucine-rich repeat kinase 2 (LRRK2) inhibitor with a mean IC 50 of 2.3 nM in vivo
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 . MCE has not independently confirmed the accuracy of these methods. They are for reference only. 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.
Form:Solid
IC50& Target:IC50: 2.3 nM (LRRK2 in vivo)
Taxonomy Tree
| Kingdom | Organic compounds |
|---|---|
| Superclass | Organoheterocyclic compounds |
| Klasse | Pyrrolopyrimidines |
| Subclass | Pyrrolo[2,3-d]pyrimidines |
| Intermediate Tree Nodes | Not available |
| Direct Parent | Pyrrolo[2,3-d]pyrimidines |
| Alternative Parents | Dialkylarylamines Aminopyrimidines and derivatives N-methylpyrroles Morpholines Imidolactams Heteroaromatic compounds Oxacyclic compounds Nitriles Dialkyl ethers Azacyclic compounds Hydrocarbon derivatives |
| Molecular Framework | Aromatic heteropolycyclic compounds |
| Substituents | Pyrrolo[2,3-d]pyrimidine - Dialkylarylamine - Aminopyrimidine - Morpholine - N-methylpyrrole - Oxazinane - Pyrimidine - Substituted pyrrole - Imidolactam - Pyrrole - Heteroaromatic compound - Ether - Dialkyl ether - Nitrile - Carbonitrile - Azacycle - Oxacycle - Amine - Organooxygen compound - Organonitrogen compound - Organic nitrogen compound - Organic oxygen compound - Hydrocarbon derivative - Cyanide - Aromatic heteropolycyclic compound |
| Beschreibung | This compound belongs to the class of organic compounds known as pyrrolo[2,3-d]pyrimidines. These are aromatic heteropolycyclic compounds containing a pyrrolo[2,3-d]pyrimidine ring system, which is an pyrrolopyrimidine isomers having the 3 ring nitrogen atoms at the 1-, 5-, and 7-positions. |
| External Descriptors | Not available |
| Activity Type | Activity Value -log(M) | Mechanism of Action | Activity Reference | Publications (PubMed IDs) |
|---|
| Löslichkeit | DMSO : 10.42 mg/mL (33.79 mM; Need ultrasonic) |
|---|---|
| Molekulargewicht | 308.340 g/mol |
| XLogP3 | 1.200 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 5 |
| Rotatable Bond Count | 2 |
| Exact Mass | 308.139 Da |
| Monoisotopic Mass | 308.139 Da |
| Topological Polar Surface Area | 82.800 Ų |
| Heavy Atom Count | 23 |
| Formal Charge | 0 |
| Complexity | 472.000 |
| Isotope Atom Count | 0 |
| Defined Atom Stereocenter Count | 0 |
| Undefined Atom Stereocenter Count | 0 |
| Defined Bond Stereocenter Count | 0 |
| Undefined Bond Stereocenter Count | 0 |
| The total count of all stereochemical bonds | 0 |
| Covalently-Bonded Unit Count | 1 |
