CZC-25146LRRK2 inhibitor CAS# 1191911-26-8 |
- Laminin (925-933)
Catalog No.:BCC1015
CAS No.:110590-60-8
- Epidermal Growth Factor Receptor Peptide (985-996)
Catalog No.:BCC1014
CAS No.:96249-43-3
Quality Control & MSDS
Number of papers citing our products
Chemical structure
3D structure
| Cas No. | 1191911-26-8 | SDF | Download SDF |
| PubChem ID | 44252884 | Appearance | Powder |
| Formula | C22H25FN6O4S | M.Wt | 488.54 |
| Type of Compound | N/A | Storage | Desiccate at -20°C |
| Solubility | DMSO : ≥ 46 mg/mL (94.16 mM) *"≥" means soluble, but saturation unknown. | ||
| Chemical Name | N-[2-[[5-fluoro-2-(2-methoxy-4-morpholin-4-ylanilino)pyrimidin-4-yl]amino]phenyl]methanesulfonamide | ||
| SMILES | COC1=C(C=CC(=C1)N2CCOCC2)NC3=NC=C(C(=N3)NC4=CC=CC=C4NS(=O)(=O)C)F | ||
| Standard InChIKey | XXHHOTZUJIXPJX-UHFFFAOYSA-N | ||
| Standard InChI | InChI=1S/C22H25FN6O4S/c1-32-20-13-15(29-9-11-33-12-10-29)7-8-19(20)26-22-24-14-16(23)21(27-22)25-17-5-3-4-6-18(17)28-34(2,30)31/h3-8,13-14,28H,9-12H2,1-2H3,(H2,24,25,26,27) | ||
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it. |
||
| About Packaging | 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment. |
||
| Shipping Condition | Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request. | ||
| Description | Potent LRRK2 inhibitor (IC50 values are 4.76 and 6.87 nM for for wild-type and G2019S mutant forms of LRRK2, respectively). Also inhibits PLK4, GAK, TNK1, CAMKK2 and PIP4K2. Attenuates mutant LRRK2-induced injury of cultured rodent and human neurons. Cell permeable. |
CZC-25146 Dilution Calculator
CZC-25146 Molarity Calculator
| 1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
| 1 mM | 2.0469 mL | 10.2346 mL | 20.4692 mL | 40.9383 mL | 51.1729 mL |
| 5 mM | 0.4094 mL | 2.0469 mL | 4.0938 mL | 8.1877 mL | 10.2346 mL |
| 10 mM | 0.2047 mL | 1.0235 mL | 2.0469 mL | 4.0938 mL | 5.1173 mL |
| 50 mM | 0.0409 mL | 0.2047 mL | 0.4094 mL | 0.8188 mL | 1.0235 mL |
| 100 mM | 0.0205 mL | 0.1023 mL | 0.2047 mL | 0.4094 mL | 0.5117 mL |
| * Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations. | |||||
Calcutta University
University of Minnesota
University of Maryland School of Medicine
University of Illinois at Chicago
The Ohio State University
University of Zurich
Harvard University
Colorado State University
Auburn University
Yale University
Worcester Polytechnic Institute
Washington State University
Stanford University
University of Leipzig
Universidade da Beira Interior
The Institute of Cancer Research
Heidelberg University
University of Amsterdam
University of Auckland
TsingHua University
The University of Michigan
Miami University
DRURY University
Jilin University
Fudan University
Wuhan University
Sun Yat-sen University
Universite de Paris
Deemed University
Auckland University
The University of Tokyo
Korea University
CZC-25146 is a selective and cell-penetrant inhibitor of leucine-rich repeat kinase-2 (LRRK2) with IC50 value of 4.76nM [1].
CZC-25146 is a second generation inhibitor of LRRK2 with excellent potency and selectivity. In a time-resolved fluorescence resonance energy transfer assay, CZC-25146 shows potent inhibition of both recombinant human wild type LRRK2 and G2019S mutant LRRK2 with IC50 values of 4.76nM and 6.87nM, respectively. CZC-25146 is selective against LRRK2. When treated with 184 different protein kinases and one lipid kinase, CZC-25146 inhibits only five of them with high potency including PLK4, GAK, TNK1, CAMKK2 and PIP4K2C. Besides that, CZC-25146 is found to relieve the G2019S LRRK2-induced cell injury and death with EC50 value of 100nM in neurons of primary rodent cortical. It also attenuates G2019S LRRK2-induced human neuronal injury with EC50 value of 4nM. However, CZC-25146 lacks sufficient brain exposure to be used in rodent models of PD [1, 2].
References:
[1] Ramsden N, Perrin J, Ren Z, et al. Chemoproteomics-based design of potent LRRK2-selective lead compounds that attenuate Parkinson’s disease-related toxicity in human neurons. ACS chemical biology, 2011, 6(10): 1021-1028.
[2] Troxler T, Greenidge P, Zimmermann K, et al. Discovery of novel indolinone-based, potent, selective and brain penetrant inhibitors of LRRK2. Bioorganic & medicinal chemistry letters, 2013, 23(14): 4085-4090.
- 10-Hydroxyscandine
Catalog No.:BCN6078
CAS No.:119188-47-5
- Coronarin B
Catalog No.:BCN6077
CAS No.:119188-38-4
- Coronarin D
Catalog No.:BCN6076
CAS No.:119188-37-3
- Coronarin A
Catalog No.:BCN6075
CAS No.:119188-33-9
- Glychionide A
Catalog No.:BCN3250
CAS No.:119152-50-0
- 3-Oxosapriparaquinone
Catalog No.:BCN3153
CAS No.:119139-56-9
- B-Raf inhibitor 1 dihydrochloride
Catalog No.:BCC4183
CAS No.:1191385-19-9
- Ganomycin I
Catalog No.:BCN3504
CAS No.:1191255-15-8
- IOWH-032
Catalog No.:BCC3922
CAS No.:1191252-49-9
- 1-Acetoxy-5-deacetylbaccatin I
Catalog No.:BCN6357
CAS No.:119120-27-3
- Linolenic acid ethyl ester
Catalog No.:BCN8333
CAS No.:1191-41-9
- Phellolactone
Catalog No.:BCN3467
CAS No.:1190897-23-4
- CZC 54252 hydrochloride
Catalog No.:BCC6218
CAS No.:1191911-27-9
- 4-(1H-1,2,4-Triazol-1-ylmethyl)aniline
Catalog No.:BCC8645
CAS No.:119192-10-8
- PHT-427
Catalog No.:BCC2554
CAS No.:1191951-57-1
- LX7101 HCL
Catalog No.:BCC6414
CAS No.:1192189-69-7
- Gomisin S
Catalog No.:BCN3622
CAS No.:119239-49-5
- Avibactam
Catalog No.:BCC1384
CAS No.:1192500-31-4
- Scutellarin methylester
Catalog No.:BCN2828
CAS No.:119262-68-9
- PE 154
Catalog No.:BCC7858
CAS No.:1192750-33-6
- Rocuronium Bromide
Catalog No.:BCC1068
CAS No.:119302-91-9
- Atalantoflavone
Catalog No.:BCN4857
CAS No.:119309-02-3
- Pinobanksin 5-methyl ether
Catalog No.:BCN7775
CAS No.:119309-36-3
- 2-Benzyl-2-(dimethylamino)-4'-morpholinobutyrophenone
Catalog No.:BCC8563
CAS No.:119313-12-1
Generation of iPSCs carrying a common LRRK2 risk allele for in vitro modeling of idiopathic Parkinson's disease.[Pubmed:29513666]
PLoS One. 2018 Mar 7;13(3):e0192497.
Induced pluripotent stem cells (iPSCs) have recapitulated several aspects of Parkinson's disease (PD), but most iPSCs are derived from familial cases, which account for only about 15% of patients. Thus, while the emphasis has justifiably been on using iPSCs to model rare familial cases, models for the most common forms of PD are critically lacking. Here, we report the generation of an iPSC-based model of idiopathic PD (iPD) with or without RS1491923, which is a common risk variant in the LRRK2 locus. Consistent with GWA studies, we found large variability in our datasets. However, iPSC-derived neurons carrying the risk allele emerged for displaying subtle disturbances of cellular degradative systems, in line with familial PD models. We also observed that treatment with the LRRK2 inhibitor CZC-25146 slightly reduced a marker of aSYN pathology in all iPD lines. Future iPSC-based studies may need to be structured similarly to large GWA studies in order to obtain relevant statistical power. However, results from this pilot study suggest that iPSC-based modeling represents an attractive way to investigate idiopathic diseases.
Chemoproteomics-based design of potent LRRK2-selective lead compounds that attenuate Parkinson's disease-related toxicity in human neurons.[Pubmed:21812418]
ACS Chem Biol. 2011 Oct 21;6(10):1021-8.
Leucine-rich repeat kinase-2 (LRRK2) mutations are the most important cause of familial Parkinson's disease, and non-selective inhibitors are protective in rodent disease models. Because of their poor potency and selectivity, the neuroprotective mechanism of these tool compounds has remained elusive so far, and it is still unknown whether selective LRRK2 inhibition can attenuate mutant LRRK2-dependent toxicity in human neurons. Here, we employ a chemoproteomics strategy to identify potent, selective, and metabolically stable LRRK2 inhibitors. We demonstrate that CZC-25146 prevents mutant LRRK2-induced injury of cultured rodent and human neurons with mid-nanomolar potency. These precise chemical probes further validate this emerging therapeutic strategy. They will enable more detailed studies of LRRK2-dependent signaling and pathogenesis and accelerate drug discovery.
