Art. -Nr.: HY-16936

JH-II-127

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JH-II-127 is an orally active, highly potent, selective and brain-permeable LRRK2 inhibitor, with IC₅₀s of 6, 2 and 48 nM for wild-type LRRK2 and LRRK2-G2019S and mutant LRRK2-A2016T. JH-II-127 inhibits Ser935 phosphorylation in all tissues of mice, including the brain. JH-II-127 can be used in the study of parkinson's syndrome.

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Reinheit: 98.0%
CAS. Nr.: 1700693-08-8
Formel: C₁₉H₂₁ClN₆O₃
Molecular Weight:416.86

Speicherung:

Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 2 years , -20°C, 1 year

JH-II-127 Chemical Structure

CAS. Nr.: 1700693-08-8

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Biologische Aktivität
- Beschreibung
- In Vitro
- In Vivo
Chemical Information
Lösungsmittel & Löslichkeit
- In Vitro
- In Vivo
Reinheit & Dokumentation
Verweise
Help & FAQs
Classifications
Bioz

Biologische Aktivität

Beschreibung

In Vitro

JH-II-127 (0.03, 0.1, 0.3, 1, 3 µM; 90 min) inhibits LRRK2 in HEK293 cells^[1].
JH-II-127 (0.3, 1, 3 µM; 90 min) inhibits endogenously expressed LRRK2 in mouse Swiss 3T3 cells^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Western Blot Analysis^[1]

Cell Line:

HEK293 cells (expressing GFP-LRRK2, GFP-LRRK2[G2019S], GFP-LRRK2[G2019S + A2016T], and GFP-LRRK2[A2016T], respectively)
Concentration:

0.03, 0.1, 0.3, 1, 3 µM
Incubation Time:

90 min
Result:

Induced a dose-dependent inhibition of Ser910 and Ser935 phosphorylation in both wild-type LRRK2 and LRRK2[G2019S] stably transfected into HEK293 cells.
Inhibited phosphorylation of Ser910 and Ser935 at approximately 0.3 μM for wild-type LRRK2 and LRRK2[G2019S].
Induced dephosphorylation of Ser910 and Ser935 at a concentration of 0.3-1 μM in the drug-resistant LRRK2[A2016T + G2019S] and LRRK2[A2016T] mutants.

Western Blot Analysis^[1]

Cell Line:

Mouse Swiss 3T3 cells
Concentration:

0.03, 0.1, 0.3, 1, 3 µM
Incubation Time:

90 min
Result:

Induced similar dose-dependent Ser935 dephosphorylation of endogenous LRRK2.

In Vivo

JH-II-127 (100 mg/kg; i.p.; single) results in near complete dephosphorylation of Ser935 of LRRK2 in all tissues including brain^[1].
1.19 Pharmacokinetic Parameters of JH-II-127 in Wild type male C57BL/6 mice^[1].

matrix	route	T_max (h)	C₀/C_max (ng/mL)	AUC_Last (h•ng/mL)	AUG_INF (h•ng/mL)	T_1/2 (h)	CL (mL/min/kg)	V_ss (L/kg)
plasma	IV (2 mg/kg)	-	1604.47	532.67	535.57	0.66	62.24	1.73
plasma	PO (10 mg/kg)	1	802.72	3094.58	3867.07	-	-	-
brain	IV (2 mg/kg)	-	1343.6	239.31	246.47	0.23	135.24	1.7
brain	PO (10 mg/kg)	1	247.35	688.21	762.38	-	-	-

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:

Wild type male C57BL/6 mice^[1].
Dosage:

2 mg/kg (for i.v.); 10 mg/kg (for p.o.); 10, 30, 100 mg/kg (for i.p.)
Administration:

Intravenous and intraperitoneal injection; oral administration; single.
Result:

Led to near complete dephosphorylation of Ser935 of LRRK2 in all tissues including brain when at 100 mg/kg of i.p. and near complete inhibition in all tissues at 30 mg/kg but only partial inhibition in brain at the 10 mg/kg dose.
Demonstrated good oral bioavailability.

Chemical Information

CAS. Nr. 1700693-08-8
Appearance Solid
Molecular Weight 416.86
Formel C₁₉H₂₁ClN₆O₃
Color Light yellow to yellow
SMILES

O=C(C1=CC=C(NC2=NC3=NC=C(Cl)C3=C(NC)N2)C(OC)=C1)N4CCOCC4
Versand

Room temperature in continental US; may vary elsewhere.

Speicherung

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	2 years
	-20°C	1 year

Lösungsmittel & Löslichkeit

In Vitro:

DMSO : 110 mg/mL (263.88 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

View the Complete Stock Solution Preparation Table

Preparing Stock Solutions

View the Complete Stock Solution Preparation Table

Concentration Solvent Mass

1 mg

5 mg

10 mg

Concentration

Solvent

Mass

1 mM

2.3989 mL

11.9944 mL

23.9889 mL

5 mM

0.4798 mL

2.3989 mL

4.7978 mL

10 mM

0.2399 mL

1.1994 mL

2.3989 mL

Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.

Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

Molaritätsrechner

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass Mass

Konzentration Konzentration

Volumen Volumen

Molecular Weight Molecular Weight

Verdünnungsrechner

Konzentration _{(Stammlösung)} × Volumen _{(Stammlösung)} = Konzentration _{(Ziellösung)} × Volumen _{(Ziellösung)}

Konzentration _{(Stammlösung)} Konzentration _{(Stammlösung)}

Volumen _{(Stammlösung)} Volumen _{(Stammlösung)}

Konzentration _{(Ziellösung)} Konzentration _{(Ziellösung)}

Volumen _{(Ziellösung)} Volumen _{(Ziellösung)}

In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

Stock Solution Working Solution

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

Protocol 1

Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline

Solubility: ≥ 2.75 mg/mL (6.60 mM); Clear solution

This protocol yields a clear solution of ≥ 2.75 mg/mL (saturation unknown).

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (27.5 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.

Protocol 2

Add each solvent one by one: 10% DMSO 90% Corn Oil

Solubility: ≥ 2.75 mg/mL (6.60 mM); Clear solution

This protocol yields a clear solution of ≥ 2.75 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (27.5 mg/mL) to 900 μL Corn oil, and mix evenly.

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage Dosage
mg/kg
Animal Weight (Per Animal) Animal Weight (Per Animal)
g
Dosing Volume (Per Animal) Dosing Volume (Per Animal)
μL
Number of Animals Number of Animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Please enter your animal formula composition:

%
DMSO +

Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
%
+
+
%
Tween-80 + +
%
Saline +

The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).

Working solution concentration: 0.22 mg/mL

Reinheit & Dokumentation

Select Batch:

Reinheit: 99.98%

Assay: 99.98%

ee.: 99.98%

Data Sheet (279 KB)
SDS (254 KB)
- English - EN (254 KB)
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- Deutsch - DE (254 KB)
- Norwegian - NO (254 KB)
- Español - ES (254 KB)
- Swedish - SV (254 KB)
- Italian - IT (254 KB)
- Korean - KR (254 KB)
- Portuguese - PT (254 KB)
COA (2659 KB)
Elemental Analysis Report (2659 KB)
HNMR (2659 KB)
CNMR (2659 KB)
RP-HPLC (2659 KB)
NP-HPLC (2659 KB)
MS (2659 KB)
LCMS (2659 KB)
IR (2659 KB)
GC (2659 KB)
OR (2659 KB)
SDS-PAGE (2659 KB)
SEC-HPLC (2659 KB)
Other Report (2659 KB)
Handling Instructions (2659 KB)

Verweise

[1]. Hatcher JM, et al. Discovery of a Pyrrolopyrimidine (JH-II-127), a Highly Potent, Selective, and Brain Penetrant LRRK2 Inhibitor. ACS Med Chem Lett. 2015 Apr 7;6(5):584-9. [Content Brief]

Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

Complete Stock Solution Preparation Table

Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

Optional Solvent	Concentration Solvent Mass	1 mg	5 mg	10 mg	25 mg
DMSO	1 mM	2.3989 mL	11.9944 mL	23.9889 mL	59.9722 mL
	5 mM	0.4798 mL	2.3989 mL	4.7978 mL	11.9944 mL
	10 mM	0.2399 mL	1.1994 mL	2.3989 mL	5.9972 mL
	15 mM	0.1599 mL	0.7996 mL	1.5993 mL	3.9981 mL
	20 mM	0.1199 mL	0.5997 mL	1.1994 mL	2.9986 mL
	25 mM	0.0960 mL	0.4798 mL	0.9596 mL	2.3989 mL
	30 mM	0.0800 mL	0.3998 mL	0.7996 mL	1.9991 mL
	40 mM	0.0600 mL	0.2999 mL	0.5997 mL	1.4993 mL
	50 mM	0.0480 mL	0.2399 mL	0.4798 mL	1.1994 mL
	60 mM	0.0400 mL	0.1999 mL	0.3998 mL	0.9995 mL
	80 mM	0.0300 mL	0.1499 mL	0.2999 mL	0.7497 mL
	100 mM	0.0240 mL	0.1199 mL	0.2399 mL	0.5997 mL

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JH-II-127

Orally Active Compound Library

Anti-Parkinson's Disease Compound Library

Neurodegenerative Disease-related Compound Library

Heterocyclic Compound Library

Highly Selective Inhibitors Library

Serine/Threonine Kinase Inhibitor Library

Bioactive Compound Library Max

MCE Bioactive Compound Library

Bioactive Compound Library

Protein Kinase Compound Library

High-Throughput Bioactive Compound Library

Posttranslational Modification Library

Kinase Inhibitor Library

CNS-Penetrant Compound Library

Autophagy Compound Library

Biologische Aktivität

Chemical Information

Lösungsmittel & Löslichkeit

Reinheit & Dokumentation

Verweise

Help & FAQs

Complete Stock Solution Preparation Table

JH-II-127

Orally Active Compound Library

Anti-Parkinson's Disease Compound Library

Neurodegenerative Disease-related Compound Library

Heterocyclic Compound Library

Highly Selective Inhibitors Library

Serine/Threonine Kinase Inhibitor Library

Bioactive Compound Library Max

MCE Bioactive Compound Library

Bioactive Compound Library

Protein Kinase Compound Library

High-Throughput Bioactive Compound Library

Posttranslational Modification Library

Kinase Inhibitor Library

CNS-Penetrant Compound Library

Autophagy Compound Library

Biologische Aktivität

Chemical Information

Lösungsmittel & Löslichkeit

Reinheit & Dokumentation

Verweise

Help & FAQs

Complete Stock Solution Preparation Table

JH-II-127 Related Classifications

HY-16936 Related Classifications