LRRK2-IN-7 is a specific, CNS-permeable (penetrable) LRRK2 kinase inhibitor (antagonist) with IC50 of 0.9 nM. LRRK2-IN-7 is more than 1000 times more selective than other kinases, ion channels and CYP enzymes.

Physicochemical Properties

Molecular Formula	C24H26N6O
Molecular Weight	414.502844333649
Exact Mass	414.216
CAS #	2307277-93-4
Related CAS #	(R,R)-LRRK2-IN-7;2307277-92-3
PubChem CID	156493868
Appearance	Off-white to pink solid powder
LogP	3.2
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	4
Heavy Atom Count	31
Complexity	773
Defined Atom Stereocenter Count	2
SMILES	[C@]1(C2=CC3=C(C=C2)C=NN3C2C=C(N3CC[C@@H](C(O)(C)C)C3)N=CN=2)(C#N)C2(CC2)C1
InChi Key	JCQABEJXHUSDMF-HOYKHHGWSA-N
InChi Code	InChI=1S/C24H26N6O/c1-22(2,31)18-5-8-29(12-18)20-10-21(27-15-26-20)30-19-9-17(4-3-16(19)11-28-30)24(14-25)13-23(24)6-7-23/h3-4,9-11,15,18,31H,5-8,12-13H2,1-2H3/t18-,24-/m1/s1
Chemical Name	(2S)-2-[1-[6-[(3R)-3-(2-hydroxypropan-2-yl)pyrrolidin-1-yl]pyrimidin-4-yl]indazol-6-yl]spiro[2.2]pentane-2-carbonitrile
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)

Biological Activity

Targets	IC50: 0.9 nM (LRRK2 Kinase)[1]
ln Vitro	LRRK2-IN-7, also known as compound 25, exhibits dual properties as a strong human BCRP inhibitor (BCRP IC50 = 0.12 μM) and a mouse breast cancer resistance protein (BCRP) substrate (mouse/human BCRP) [1].
ln Vivo	LRRK2-IN-7 (compound 25) was tolerated up to 100 mg/kg once daily (AUCtot = 330 μM·h) in a 7-day dose-limiting toxicity trial in rats [1]. LRRK2-IN-7 (compound 25) demonstrated a dose-dependent decrease in LRRK2 pS935 in the rat brain striatum with EC50 = 0.18 nM in an acute (2-hour) PK/PD study[1].
References	[1]. Discovery and Optimization of Potent, Selective, and Brain-Penetrant 1-Heteroaryl-1 H-Indazole LRRK2 Kinase Inhibitors for the Treatment of Parkinson's Disease. J Med Chem. 2022 Dec 22;65(24):16801-16817.

Solubility Data

Solubility (In Vitro)

DMSO : 100 mg/mL (241.25 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (6.03 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 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.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.4125 mL	12.0627 mL	24.1255 mL
	5 mM	0.4825 mL	2.4125 mL	4.8251 mL
	10 mM	0.2413 mL	1.2063 mL	2.4125 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.