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438195 LRRK2 Inhibitor III, HG-10-102-01 - Calbiochem

438195
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Panoramica

Replacement Information

Products

Numero di catalogoConfezionamento Qtà/conf
438195-10MG Bottiglia di vetro 10 mg
Description
OverviewA cell-permeable 2,4-diaminopyrimidinyl compound that acts as a potent, ATP-competitive LRRK2-selective inhibitor (IC5050 = 20.3, 3.2, 153.7 and 95.9 nM, respectively,against human wt LRRK2 and G2019S, A2016T, G2019S/A2016T LRRK2 mutant; [ATP] = 100 µM), displaying much reduced potency against MNK2 and MLK1 (IC50 = 0.6 and 2.1 µM, respectively; [ATP] = 100 µM) and little activity toward a panel of 136 other kinases. Although both HG-10-102-01 and LRRK2-In-1 (Cat. No. 438193) inhibit cellular wt and G20195 LRRK2 phosphorylation (Optimal conc. 1 to 3 µM), only HG-10-102-01 is effective against cellular A2016T and G2019S/A2016T LRRK2 phosphorylations (IC50 <3 µM). And only HG-10-102-01, but not LRRK2-In-1 or CZC-25146 (Cat. No. 438194), can cross blood-brain-barrier for LRRK2 phosphorylation inhibition in mice (30 mg/kg to 50 mg/kg i.p.) in vivo.
Catalogue Number438195
Brand Family Calbiochem®
Synonyms(4-(5-Chloro-4-(methylamino)pyrimidin-2-ylamino)-3-methoxyphenyl)(morpholino)methanone, Mixed-Lineage Kinase 1 Inhibitor I, MLK1 Inhibitor I, MNK Inhibitor III, Leucine-Rich Repeat Kinase 2 Inhibitor III
References
ReferencesChoi, H.G., et al. 2012. ACS Med. Chem. Lett. 3, 658.
Product Information
FormOff-white powder
Hill FormulaC₁₇H₂₀ClN₅O₃
Chemical formulaC₁₇H₂₀ClN₅O₃
ReversibleY
Structure formula ImageStructure formula Image
Quality LevelMQ100
Applications
Biological Information
Primary TargetLRRK2
Primary Target IC<sub>50</sub>20.3, 3.2, 153.7 and 95.9 nM, respectively, against Nictide phosphorylation by recombinant human wt LRRK2 and G2019S, A2016T, G2019S/A2016T LRRK2 mutant constructs
Purity≥99% by HPLC
Physicochemical Information
Cell permeableY
Dimensions
Materials Information
Toxicological Information
Safety Information according to GHS
Safety Information
Product Usage Statements
Storage and Shipping Information
Ship Code Ambient Temperature Only
Toxicity Standard Handling
Storage +2°C to +8°C
Protect from Light Protect from light
Do not freeze Ok to freeze
Special InstructionsFollowing reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.
Packaging Information
Packaged under inert gas Packaged under inert gas
Transport Information
Supplemental Information
Specifications

Documentation

Riferimenti bibliografici

Panoramica delle referenze
Choi, H.G., et al. 2012. ACS Med. Chem. Lett. 3, 658.
Scheda tecnica

Note that this data sheet is not lot-specific and is representative of the current specifications for this product. Please consult the vial label and the certificate of analysis for information on specific lots. Also note that shipping conditions may differ from storage conditions.

Revision28-March-2013 JSW
Synonyms(4-(5-Chloro-4-(methylamino)pyrimidin-2-ylamino)-3-methoxyphenyl)(morpholino)methanone, Mixed-Lineage Kinase 1 Inhibitor I, MLK1 Inhibitor I, MNK Inhibitor III, Leucine-Rich Repeat Kinase 2 Inhibitor III
DescriptionA cell-permeable 2,4-diaminopyrimidinyl compound that acts as a potent, ATP-competitive LRRK2-selective inhibitor (IC50 = 20.3, 3.2, 153.7 and 95.9 nM, respectively, against Nictide phosphorylation by recombinant human wt LRRK2 and G2019S, A2016T, G2019S/A2016T LRRK2 mutant constructs; [ATP] = 100 µM), displaying much reduced potency against MNK2 and MLK1 (IC50 = 0.6 and 2.1 µM, respectively; [ATP] = 100 µM) and little or no activity toward a panel of 136 other kinases. While both HG-10-102-01 and LRRK2-IN-1 (Cat. No. 438193) inhibit Ser910/Ser395 phosphorylation of wt and G20195 LRRK2 in human and murine cultures with similar potency (Optimal conc. 1 to 3 µM), only HG-10-102-01 is effective toward cellular phosphorylation of A2016T and G2019S/A2016T LRRK2 mutants (IC50 <3 µM). And only HG-10-102-01, but not LRRK2-IN-1 or CZC-25146 (Cat. No. 438194), can cross blood-brain-barrier and effectively inhibit brain LRRK2 phosphorylation in mice (by 40% and 70%, respectively, 1 h after i.p. dose of 30 mg/kg and ≥50 mg/kg) in vivo despite its low metabolic stability both in vitro (T1/2 = 13 min in mouse liver microsome) and in vivo (Plasma T1/2 = 0.13 h and AUClast = 74.85 h·ng/mL; 1 mg/kg via i.v.).
FormOff-white powder
Intert gas (Yes/No) Packaged under inert gas
Chemical formulaC₁₇H₂₀ClN₅O₃
Structure formulaStructure formula
Purity≥99% by HPLC
SolubilityDMSO (100 mg/ml)
Storage +2°C to +8°C
Protect from light
Do Not Freeze Ok to freeze
Special InstructionsFollowing reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.
Toxicity Standard Handling
ReferencesChoi, H.G., et al. 2012. ACS Med. Chem. Lett. 3, 658.