PF-06447475
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PF-06447475 ??
- ???
- >223°C (dec.)
- ??
- 1.40±0.1 g/cm3(Predicted)
- ?? ??
- room temp
- ???
- DMSO: ???10mg/mL, ??
- ?? ?? (pKa)
- 12.96±0.50(Predicted)
- ??? ??
- ??
- ??
- ???? ????
- InChI
- InChI=1S/C17H15N5O/c18-9-12-2-1-3-13(8-12)14-10-19-16-15(14)17(21-11-20-16)22-4-6-23-7-5-22/h1-3,8,10-11H,4-7H2,(H,19,20,21)
- InChIKey
- BHTWDJBVZQBRKP-UHFFFAOYSA-N
- SMILES
- C(#N)C1=CC=CC(C2C3=C(N4CCOCC4)N=CN=C3NC=2)=C1
PF-06447475 C??? ??, ??, ??
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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.?? ???
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 overexpressionPF-06447475 ?? ?? ? ???
???
Benzonitrile, 3-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-
7H-Pyrrolo[2,3-d]pyrimidine, 4-chloro-5-iodo-7-[[2-(trimethylsilyl)ethoxy]methyl]-
4-Chloro-5-iodo-7H-pyrrol[2,3-d]pyrimidine
3-Cyanophenylboronic acid
????
N,N-????????????
tert-?????
?? ??
PF-06447475 ?? ??
???( 118)?? ??
| ??? | ?? | ??? | ?? | ?? ? | ?? |
|---|---|---|---|---|---|
| ATK CHEMICAL COMPANY LIMITED | +undefined-21-51877795 |
ivan@atkchemical.com | China | 33024 | 60 |
| career henan chemical co | +86-0371-86658258 |
sales@coreychem.com | China | 29812 | 58 |
| Alchem Pharmtech,Inc. | 8485655694 |
sales@alchempharmtech.com | United States | 63687 | 58 |
| TargetMol Chemicals Inc. | +1-781-999-5354; +1-00000000000 |
marketing@targetmol.com | United States | 32468 | 58 |
| HANGZHOU CLAP TECHNOLOGY CO.,LTD | 86-571-88216897,88216896 13588875226 |
sales@hzclap.com | CHINA | 6312 | 58 |
| Zhejiang J&C Biological Technology Co.,Limited | +1-2135480471 |
sales@sarms4muscle.com | China | 10457 | 58 |
| InvivoChem | +1-708-310-1919 +1-13798911105 |
sales@invivochem.cn | United States | 6391 | 58 |
| Nantong HI-FUTURE Biology Co., Ltd. | +86-18051384581 |
sales@chemhifuture.com | China | 3135 | 58 |
| ShenZhen Trendseen Biological Technology Co.,Ltd. | 13417589054 |
trendseenbio@gmail.com | China | 11680 | 58 |
| Zibo Hangyu Biotechnology Development Co., Ltd | +86-0533-2185556 +86-15965530500 |
nickzhang@hangyubiotech.com | China | 9941 | 58 |
PF-06447475 ?? ??:
N-Methyl-N-[2-[[[2-[(2-oxo-2,3-dihydro-1H-indol-5-yl)amino]-5-trifluoromethylpyrimidin-4-yl]amino]methyl]phenyl]methanesulfonamide
PF 573228
PF-06882961
6-chloro-5-(4-(1-hydroxycyclobutyl)phenyl)-1H-indole-3-carboxylicacid
PF-04979064
PF-3758309
PF-05212384
PF-06281355
PF-562271
Ketohexokinase inhibitor 1
PF-6274484
PF-9366
4-[(Diethylamino)methyl]-N-[2-(2-methoxyphenyl)ethyl]-N-(3R)-3-pyrrolidinylbenzamide
3-(5-fluoro-indol-3-yl)-pyrrolidine-2,5-dione
PF06869206
PF-06650833
Ritlecitinib
brepocitinib