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

438195
  
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      Overview

      Replacement Information
      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®
      SynonymsMixed-Lineage Kinase 1 Inhibitor I, MLK1 Inhibitor I, MNK Inhibitor III, Leucine-Rich Repeat Kinase 2 Inhibitor III, (4-(5-Chloro-4-(methylamino)pyrimidin-2-ylamino)-3-methoxyphenyl)(morpholino)methanone
      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
      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

      References

      Reference overview
      Choi, H.G., et al. 2012. ACS Med. Chem. Lett. 3, 658.
      Data Sheet

      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
      SynonymsMixed-Lineage Kinase 1 Inhibitor I, MLK1 Inhibitor I, MNK Inhibitor III, Leucine-Rich Repeat Kinase 2 Inhibitor III, (4-(5-Chloro-4-(methylamino)pyrimidin-2-ylamino)-3-methoxyphenyl)(morpholino)methanone
      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.