JH-II-127 | CAS#1700693-08-8 | LRRK2 inhibitor

MedKoo Cat#: 522462 | Name: JH-II-127

Description:

WARNING: This product is for research use only, not for human or veterinary use.

JH-II-127 is a potent and selective inhibitor of both wild-type and G2019S mutant LRRK2. JH-II-127 substantially inhibits Ser910 and Ser935 phosphorylation of both wild-type LRRK2 and G2019S mutant at a concentration of 0.1-0.3 μM in a variety of cell types and is capable of inhibiting Ser935 phosphorylation in mouse brain following oral delivery of doses as low as 30 mg/kg. Activating mutations in leucine-rich repeat kinase 2 (LRRK2) are present in a subset of Parkinson's disease (PD) patients and may represent an attractive therapeutic target.

Chemical Structure

JH-II-127

CAS#1700693-08-8

Theoretical Analysis

MedKoo Cat#: 522462

Name: JH-II-127

CAS#: 1700693-08-8

Chemical Formula: C19H21ClN6O3

Exact Mass: 416.1364

Molecular Weight: 416.87

Elemental Analysis: C, 54.74; H, 5.08; Cl, 8.50; N, 20.16; O, 11.51

Price and Availability

Size	Price	Availability	Quantity
5mg	USD 250.00	2 Weeks
10mg	USD 450.00	2 Weeks

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Synonym

JH-II-127; JH-II 127; JH-II127.

IUPAC/Chemical Name

(4-((5-chloro-4-(methylamino)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)amino)-3-methoxyphenyl)(morpholino)methanone

InChi Key

HUEKBQXFNHWTQQ-UHFFFAOYSA-N

InChi Code

InChI=1S/C19H21ClN6O3/c1-21-16-15-12(20)10-22-17(15)25-19(24-16)23-13-4-3-11(9-14(13)28-2)18(27)26-5-7-29-8-6-26/h3-4,9-10H,5-8H2,1-2H3,(H3,21,22,23,24,25)

SMILES Code

ClC1=CNC2=C1C(NC)=NC(NC3=C(OC)C=C(C(N4CCOCC4)=O)C=C3)=N2

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO, not in water

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Instruction

View handling instruction

Biological target:

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.

In vitro activity:

Compound 18 (JH-II-127) induced a dose-dependent inhibition of Ser910 and Ser935 phosphorylation in both wild-type LRRK2 and LRRK2[G2019S] stably transfected into HEK293 cells (Figure 3a). Reference: ACS Med Chem Lett. 2015 Apr 7;6(5):584-9. https://pubmed.ncbi.nlm.nih.gov/26005538/

In vivo activity:

With 18 (JH-II-127), this study observed near complete inhibition in all tissues at 30 mg/kg but only partial inhibition in mouse brain at the 10 mg/kg dose. These results indicate that 18 is a promising chemotype for achieving dephosphorylation of Ser935 in the brain. Reference: ACS Med Chem Lett. 2015 Apr 7;6(5):584-9. https://pubmed.ncbi.nlm.nih.gov/26005538/

	Solvent	mg/mL	mM
Solubility
	DMSO	75.9	181.94

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 416.87 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Hatcher JM, Zhang J, Choi HG, Ito G, Alessi DR, Gray NS. 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. doi: 10.1021/acsmedchemlett.5b00064. PMID: 26005538; PMCID: PMC4434483.

In vitro protocol:

In vivo protocol:

1: Hatcher JM, Zhang J, Choi HG, Ito G, Alessi DR, Gray NS. 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. doi: 10.1021/acsmedchemlett.5b00064. eCollection 2015 May 14. PubMed PMID: 26005538; PubMed Central PMCID: PMC4434483.