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CZC-25146 freebase

Cat No.:V2153 Purity: ≥98%
CZC-25146 is a potent and selective LRRK2 inhibitor.
CZC-25146 freebase
CZC-25146 freebase Chemical Structure CAS No.: 1191911-26-8
Product category: LRRK2
This product is for research use only, not for human use. We do not sell to patients.
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Purity & Quality Control Documentation

Purity: ≥98%

Product Description

CZC-25146 is a potent and selective LRRK2 inhibitor. Leucine-rich repeat kinase-2 (LRRK2) mutations are the most important cause of familial Parkinson's disease. CZC-25146 prevents mutant LRRK2-induced injury of cultured rodent and human neurons with mid-nanomolar potency.

Biological Activity I Assay Protocols (From Reference)
ln Vitro
CZC-25146 (0.01-5 μM; 7 days) does not inhibit neuronal growth or cause cytotoxicity in human cortical neurons [1]. With an EC50 of about 100 nM, CZC-25146 (0.01-5 μM; 2 days) efficiently attenuates G2019S LRRK2-mediated toxicity in primary rodent neurons in a concentration-dependent manner [1]. Neurite abnormalities produced by LRRK2 G2019S in primary human neurons are rescued in a dose-dependent manner by CZC-25146 (0.06-1000 nM) [1]. Without compromising cell viability, CZC-25146 (14.3 and 28.6 μM; 48 hours) dramatically lowers allele Z (ATZ) polymer loading, which encodes mutant AAT, and restores AAT secretion in iPSC hepatocytes [3].
ln Vivo
In mice overexpressing the human polymer ATZ, CZC-25146 (250 mg/kg; oral; 14 days) lowers the levels of ATZ polymer [3]. After injecting CZC-25146 intravenously into mice, the drug distributes broadly throughout the animal and demonstrates comparatively acceptable pharmacokinetic features (1 mg/kg intravenously; 5 mg/kg oral; single dosage).
Cell Assay
Cytotoxicity assay[1]
Cell Types: human cortical neurons
Tested Concentrations: 0.01, 0.1, 1 and 5 μM
Incubation Duration: 7 days
Experimental Results: Concentrations below 5 μM were not harmful to human cortical neurons when treated for 7 days in culture It produces cytotoxicity to neurons and does not hinder neuronal development.
Animal Protocol
Animal/Disease Models: Male CD-1 mice[1]
Doses: 1 mg/kg, intravenous (iv) (iv)injection; 5 mg/kg orally.
Doses: intravenous (iv) (iv)injection and oral administration; single dose
Experimental Results: CZC-25146 in male CD-1 mice pharmacokinetic/PK/PK parameters [1]. iv (1 mg/kg) po (5 mg/kg) CL (L/h/kg) 2.3 Vss (L/kg) 5.4 t1/2 (h) 1.6 1 tmax (h) 0 0.25 Cmax (ng/mL) 154 1357 AUClast (ng/mL·h) 419 2878 AUCinf (ng/mL·h) 434 2894 F (%) 133
References

[1]. Chemoproteomics-based design of potent LRRK2-selective lead compounds that attenuate Parkinson's disease-related toxicity in human neurons. ACS Chem Biol. 2011 Oct 21;6(10):1021-8.

[2]. LRRK2 inhibitors and their potential in the treatment of Parkinson's disease: current perspectives. Clin Pharmacol. 2016 Oct 20;8:177-189.

[3]. Small molecule screen employing patient-derived iPS hepatocytes identifies LRRK2 as a novel therapeutic target for Alpha1 Antitrypsin Deficiency.

These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C22H25N6O4FS
Molecular Weight
488.5351
Exact Mass
488.164
CAS #
1191911-26-8
Related CAS #
CZC-25146 hydrochloride;1330003-04-7
PubChem CID
44252884
Appearance
Pale purple to purple solid powder
Density
1.4±0.1 g/cm3
Boiling Point
697.4±65.0 °C at 760 mmHg
Flash Point
375.5±34.3 °C
Vapour Pressure
0.0±2.2 mmHg at 25°C
Index of Refraction
1.655
LogP
1.5
Hydrogen Bond Donor Count
3
Hydrogen Bond Acceptor Count
11
Rotatable Bond Count
8
Heavy Atom Count
34
Complexity
737
Defined Atom Stereocenter Count
0
InChi Key
XXHHOTZUJIXPJX-UHFFFAOYSA-N
InChi Code
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)
Chemical Name
N-[2-[[5-fluoro-2-(2-methoxy-4-morpholin-4-ylanilino)pyrimidin-4-yl]amino]phenyl]methanesulfonamide
HS Tariff Code
2934.99.9001
Storage

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Shipping Condition
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
Solubility Data
Solubility (In Vitro)
DMSO : ≥ 46 mg/mL (~94.16 mM)
Solubility (In Vivo)
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.12 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

Solubility in Formulation 2: ≥ 2.5 mg/mL (5.12 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

 (Please use freshly prepared in vivo formulations for optimal results.)
Preparing Stock Solutions 1 mg 5 mg 10 mg
1 mM 2.0469 mL 10.2346 mL 20.4692 mL
5 mM 0.4094 mL 2.0469 mL 4.0938 mL
10 mM 0.2047 mL 1.0235 mL 2.0469 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.

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What is the mass of compound required to make a 10 mM stock solution in 5 ml of DMSO given that the molecular weight of the compound is 350.26 g/mol?
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  • The answer of 17.513 mg appears in the Mass box. In a similar way, you may calculate the volume and concentration.

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What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:
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Note: Chemical formula is case sensitive: C12H18N3O4  c12h18n3o4
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Definitions of molecular mass, molecular weight, molar mass and molar weight:
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In vivo Formulation Calculator (Clear solution)
Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)
Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)
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Calculation results

Working concentration mg/mL;

Method for preparing DMSO stock solution mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.

Method for preparing in vivo formulation:Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.

(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
             (2) Be sure to add the solvent(s) in order.

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