STF-3600
STF-3600 is a LRRK2G2019S inhibitor with an IC50 of 0.9 nM against the human target. It has oral activity and can cross the blood-brain barrier. STF-3600 selectively inhibits kinase activity, including autophosphorylation at Ser935 and Ser1292, as well as phosphorylation of the endogenous substrate Rab10 at Thr73. STF-3600 inhibits vacuolization of type II pulmonary epithelial cells in wild-type/heterozygous mice, while it induces this vacuolization phenotype in homozygous mice. STF-3600 can be used in Parkinson's disease research.
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- CAS No.: 2765654-79-1
- Formule: C24H21N5
- Masse moléculaire:379.46
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Stockage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Activité biologique
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Activité biologique
Description
IC50 & Target
[1]|
LRRK2G2019S 0.9 nM (IC50) |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| HEK293 | IC50 |
2.1 nM
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Inhibition of pSer935 LRRK2 in HEK293 cells stably expressing human G2019S LRRK2 incubated for 2 hrs measured by CisBio phospho-LRRK2 (Ser935) kit assay.
Inhibition of pSer935 LRRK2 in HEK293 cells stably expressing human G2019S LRRK2 incubated for 2 hrs measured by CisBio phospho-LRRK2 (Ser935) kit assay.
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42503786 |
| HEK293 | IC50 |
140 nM
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Inhibition of pSer935 LRRK2 in HEK293 cells stably expressing human WT LRRK2 incubated for 2 hrs measured by CisBio phospho-LRRK2 (Ser935) kit assay.
Inhibition of pSer935 LRRK2 in HEK293 cells stably expressing human WT LRRK2 incubated for 2 hrs measured by CisBio phospho-LRRK2 (Ser935) kit assay.
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42503786 |
| HEK293 | IC50 |
2.0 nM
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Inhibition of pSer1292 LRRK2 in HEK293 cells stably expressing human G2019S LRRK2 incubated for 2 hrs measured by MSD assay.
Inhibition of pSer1292 LRRK2 in HEK293 cells stably expressing human G2019S LRRK2 incubated for 2 hrs measured by MSD assay.
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42503786 |
| HEK293 | IC50 |
38 nM
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Inhibition of pSer1292 LRRK2 in HEK293 cells stably expressing human WT LRRK2 incubated for 2 hrs measured by MSD assay.
Inhibition of pSer1292 LRRK2 in HEK293 cells stably expressing human WT LRRK2 incubated for 2 hrs measured by MSD assay.
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42503786 |
| A549 | IC50 |
6 nM
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Inhibition of pThr73 Rab10 in human lung epithelial A549 cells expressing G2019S LRRK2 incubated for 2 hrs measured by plate reader assay with acceptor and donor mixes.
Inhibition of pThr73 Rab10 in human lung epithelial A549 cells expressing G2019S LRRK2 incubated for 2 hrs measured by plate reader assay with acceptor and donor mixes.
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42503786 |
| A549 | IC50 |
41 nM
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Inhibition of pThr73 Rab10 in human lung epithelial A549 cells expressing WT LRRK2 incubated for 2 hrs measured by plate reader assay with acceptor and donor mixes.
Inhibition of pThr73 Rab10 in human lung epithelial A549 cells expressing WT LRRK2 incubated for 2 hrs measured by plate reader assay with acceptor and donor mixes.
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42503786 |
In Vitro
STF-3600 (2 h) potently inhibits pSer935 in HEK293 cells expressing LRRK2G2019S, with an IC50 of 2.1 nM[1].
STF-3600 (2 h) potently inhibits pSer1292 in HEK293 cells expressing LRRK2G2019S, with an IC50 of 2 nM[1].
STF-3600 (2 h) inhibits pThr73 Rab10 in A549 cells expressing LRRK2G2019S, with an IC50 of 6 nM[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Parmacokinetics
In Vivo
STF-3600 (100 mg/kg/day; oral administration; daily dosing for 21 consecutive days) inhibits LRRK2G2019S in the brain tissues of heterozygous and homozygous knock-in mice. It does not induce pulmonary toxicity in wild-type or heterozygous mice, but causes pulmonary vacuolization in homozygous knock-in mice[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6J mice (male and female, 5-8 months old; wild-type, heterozygous G2019S LRRK2 knock-in, and homozygous G2019S LRRK2 knock-in)[1]
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Dosage:3 mg/kg; 10 mg/kg; 30 mg/kg; 100 mg/kg
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Administration:p.o.; single dose
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Result:Achieved maximal inhibition of pSer935 LRRK2 at 10 mg/kg in homozygous G2019S LRRK2 knock-in mouse brain and lung.
Left pSer935 LRRK2 still detectable at 100 mg/kg in wild-type mice.
Showed greater potency of pThr73 Rab10 inhibition in lung tissue of homozygous G2019S LRRK2 knock-in mice compared to wild-type mice.
Left total LRRK2 and Rab10 levels unchanged in all tissues.
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Animal Model:C57BL/6J mice (male and female, 5-8 months old; wild-type, heterozygous G2019S LRRK2 knock-in, and homozygous G2019S LRRK2 knock-in)[1]
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Dosage:100 mg/kg/day (actual average exposure 61.6 mg/kg/day)
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Administration:p.o.; daily; 21 days
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Result:Induced overt type II pneumocyte vacuolization in homozygous G2019S LRRK2 knock-in mice (112 vacuolated cells per scanned area), with no vacuolization in wild-type or heterozygous G2019S LRRK2 knock-in mice.
Reduced pSer935 LRRK2 activity to ~15% of vehicle-treated levels in homozygous knock-in mouse brain and ~50% of vehicle-treated levels in heterozygous knock-in mouse brain, with no significant effect in wild-type mouse brain.
Caused no significant changes in complete blood count measures across any genotype or gender.
Chemical Information
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CAS No. 2765654-79-1
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Masse moléculaire 379.46
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Formule C24H21N5
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SMILES
CC1=CC(C2=NNC3=CC=C(C=C23)N[C@@H]4C5=CC=C(C#N)C=C5CCC4)=CC=N1
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureté et documentation
Références
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
STF-3600 Related Classifications
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