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Purity: ≥98%
LRRK2-IN-1 (LRRK2-IN 1; LRRK2 IN-1) is a novel, highly potent and selective inhibitor of leucine-rich repeat kinase 2 (LRRK2) with anti-PD (Parkinson's disease) activity. It inhibits LRRK2 (G2019S) and LRRK2 (WT) with IC50s of 6 nM and 13 nM, respectively. Mutations in LRRK2 are closely related to late-onset autosomal dominant Parkinson's disease.
| ln Vitro |
The TR-FRET signal is 2.5 times higher in the wild-type and G2019S transduction, and this signal can be dose-dependently inhibited by LRRK2-IN-1, with IC50 values of 0.08 µM and 0.03 µM, respectively[1]. In DCLK2 inhibition, LRRK2-IN-1 had an IC50 of 45 nM. In biochemical assays for AURKB, CHEK2, MKNK2, MYLK, NUAK1, and PLK1, it has an IC50 of more than 1 µM. It has been verified that LRRK2-IN-1 inhibits MAPK7, with an EC50 of 160 nM. When LRRK2-IN-1 is stably transfected into HEK293 cells, it causes a dose-dependent inhibition of Ser910 and Ser935 phosphorylation along with the loss of 14-3-3 binding. IC50 of 49.3 µM indicates that LRRK2-IN-1 is moderately cytotoxic to HepG2 cells. In both the presence and absence of S9, LRRK2-IN-1 exhibits genotoxicity at 15.6 and 3.9 µM, respectively[3]. LRRK2-IN-1 prevents HCT116 and AsPC-1 cells from proliferating, migrating, and causing cell death with characteristics of apoptosis[4].
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| ln Vivo |
LRRK2-IN-1 (100 mg/kg, ip) causes LRRK2 to be dephosphorylated in the mice's kidney[2]. AsPC-1 tumor xenografts' tumor volume and weight significantly decrease after intraperitoneal injection of LRRK2-IN-1 (100 mg/kg)[4].
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| Additional Infomation |
LRRK2-IN-1 is a member of the class of pyrimidobenzodiazepines that is 5,11-dimethylpyrimido[4,5-b][1,4]benzodiazepin-6-one carrying at C-2 on the pyrimidine ring a 4-[(4-methylpiperazin-1-yl)piperidine-1-carbonyl]-2-methoxyanilino substituent. It is an inhibitor of the Parkinson's disease kinase LRRK2. It has a role as an EC 2.7.11.1 (non-specific serine/threonine protein kinase) inhibitor and an antineoplastic agent. It is a N-acylpiperidine, a N-alkylpiperazine, an aromatic ether, a pyrimidobenzodiazepine, an aromatic amine, a secondary amino compound and a tertiary amino compound.
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| Molecular Formula |
C31H38N8O3
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| Molecular Weight |
570.69
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| Exact Mass |
570.306
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| CAS # |
1234480-84-2
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| Related CAS # |
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| PubChem CID |
46843906
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
787.8±70.0 °C at 760 mmHg
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| Flash Point |
430.3±35.7 °C
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| Vapour Pressure |
0.0±2.7 mmHg at 25°C
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| Index of Refraction |
1.641
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| LogP |
0.36
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
42
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| Complexity |
939
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
IWMCPJZTADUIFX-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C31H38N8O3/c1-35-15-17-38(18-16-35)22-11-13-39(14-12-22)29(40)21-9-10-24(27(19-21)42-4)33-31-32-20-26-28(34-31)36(2)25-8-6-5-7-23(25)30(41)37(26)3/h5-10,19-20,22H,11-18H2,1-4H3,(H,32,33,34)
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| Chemical Name |
2-((2-methoxy-4-(4-(4-methylpiperazin-1-yl)piperidine-1-carbonyl)phenyl)amino)-5,11-dimethyl-5,11-dihydro-6H-benzo[e]pyrimido[5,4-b][1,4]diazepin-6-one
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| Synonyms |
LRRK2-IN 1; LRRK2-IN1; LRRK2-IN-1;
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.38 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 (4.38 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (4.38 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: Captisol: 17mg/mL |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7523 mL | 8.7613 mL | 17.5226 mL | |
| 5 mM | 0.3505 mL | 1.7523 mL | 3.5045 mL | |
| 10 mM | 0.1752 mL | 0.8761 mL | 1.7523 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.
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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