DC Chemicals Limited
China
Product Name: PF-06447475
Price: $550.0/100mg $1000.0/250mg $1900.0/1g
Purity: 98.0%
Stocking Period: 3 Day
Contact: Tony Cao

Dayang Chem (Hangzhou) Co., Ltd.
China
Product Name: PF-06447475
Price: $Inquiry/100g $Inquiry/1kg $Inquiry/100kg $Inquiry/1000kg
Purity: 98.0%
Stocking Period: Inquiry
Contact: Ms Wang

1527473-33-1

1527473-33-1 structure

1527473-33-1 structure

Name: PF-06447475
Chemical Name: 3-[4-(morpholin-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl]benzonitrile
CAS Number: 1527473-33-1
Molecular Formula: C₁₇H₁₅N₅O
Molecular Weight: 305.334
Catalog: Signaling Pathways Autophagy LRRK2
Create Date: 2018-04-14 18:32:12
Modify Date: 2024-01-18 18:31:58
PF-06447475 is a highly potent, selective and brain penetrant LRRK2 inhibitor with an IC50 of 3 nM.

Name	3-[4-(morpholin-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl]benzonitrile
Synonyms	pf06447475 PF-06447475 3-[4-(4-Morpholinyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl]benzonitrile Benzonitrile, 3-[4-(4-morpholinyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl]-

Description	PF-06447475 is a highly potent, selective and brain penetrant LRRK2 inhibitor with an IC50 of 3 nM.
Related Catalog	Signaling Pathways >> Autophagy >> LRRK2 Research Areas >> Neurological Disease
Target	IC50: 3 nM (LRRK2)[1].
In Vitro	PF-06447475 inhibits LRRK2 enzyme and LRRK2 in the whole cell assay with IC50s of 3 and 25 nM, respectively[1]. Cells incubated with PF-06447475 alone (0.5, 1, 3 μM) or in the presence of ROT significantly reduces (S935)-LRRK2 kinase phosphorylation to control. PF-06447475 significantly preserves the nucleus morphology and ΔΨm of NLCs exposed to ROT compared to untreated and control. PF-475 significantly diminishes ROT-induced ROS generation to a similar extent to cells exposed to PF-475 alone[2].
In Vivo	In G2019S+ rats treated with PF-06447475, a significant reduction in microgliosis to levels found in wild-type rats could be observed. The proinflammatory marker MHC-II expressed on myeloid cells but not neurons also appears to be less abundant in confocal sections in G2019S+ rats treated with PF-06447475. PF-06447475 treatment in G2019S+ rats significantly lowers the number of CD68 cells recruited to the SNpc. PF-06447475 successfully blocks the enhanced neuroinflammation associated with G2019S-LRRK2 expression. Treatment of G2019S+ rats with PF-06447475 preserves TH expression in the dorsal striatum, consistent with drug attenuating neurodegeneration in the SNpc[3]. PF-06447475 is well tolerated in rats[1].
Animal Admin	Rats: PF-06447475 are administered to the desired amount in a suspension solution consisting of 10% propylene glycol, 20% PEG-400, and 70% 0.5% methylcellulose. To determine the potency of PF-06447475 in blocking brain LRRK2 kinase activity, wild-type Sprague-Dawley rats are treated at 3 and 30 mg/kg PF-06447475 (p.o. b.i.d.) for 14 days, and total and phospho-LRRK2 are subsequently measured from brain tissue lysates[3].
References	[1]. Henderson JL, et al. Discovery and preclinical profiling of 3-[4-(morpholin-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl]benzonitrile (PF-06447475), a highly potent, selective, brain penetrant, and in vivo active LRRK2 kinase inhibitor. J Med Chem. 2015 Jan 8;58(1):419-32. [2]. Mendivil-Perez M, et al. Neuroprotective Effect of the LRRK2 Kinase Inhibitor PF-06447475 in Human Nerve-Like Differentiated Cells Exposed to Oxidative Stress Stimuli: Implications for Parkinson's Disease. Neurochem Res. 2016 Oct;41(10):2675-2692. [3]. Daher JP, et al. Leucine-rich Repeat Kinase 2 (LRRK2) Pharmacological Inhibition Abates α-Synuclein Gene-induced Neurodegeneration. J Biol Chem. 2015 Aug 7;290(32):19433-44.

Density	1.4±0.1 g/cm3
Molecular Formula	C₁₇H₁₅N₅O
Molecular Weight	305.334
Exact Mass	305.127655
PSA	77.83000
LogP	2.00
Appearance	offwhite solid
Index of Refraction	1.711
Storage condition	-20℃

Symbol	GHS06
Signal Word	Danger
Hazard Statements	H301
Precautionary Statements	P301 + P310
RIDADR	UN 2811 6.1 / PGIII