LP-935509 (LP935509) is a novel and potent inhibitor of the Adapter protein-2 Associated Kinase 1 (AAK1) with the potential to Treat Neuropathic Pain. It inhibits AAK1 with IC50 of 3.3 nM.

Physicochemical Properties

Molecular Formula	C20H24N6O3
Molecular Weight	396.442963600159
Exact Mass	396.191
Elemental Analysis	C, 60.59; H, 6.10; N, 21.20; O, 12.11
CAS #	1454555-29-3
Related CAS #	1454555-29-3;
PubChem CID	86697436
Appearance	Light yellow to yellow solid powder
LogP	2.1
Hydrogen Bond Donor Count	0
Hydrogen Bond Acceptor Count	7
Rotatable Bond Count	5
Heavy Atom Count	29
Complexity	556
Defined Atom Stereocenter Count	0
InChi Key	GOOYSJIWTIHOGW-UHFFFAOYSA-N
InChi Code	InChI=1S/C20H24N6O3/c1-14(2)29-20(27)25-11-9-24(10-12-25)17-6-8-26-18(23-17)16(13-22-26)15-5-4-7-21-19(15)28-3/h4-8,13-14H,9-12H2,1-3H3
Chemical Name	propan-2-yl 4-[3-(2-methoxypyridin-3-yl)pyrazolo[1,5-a]pyrimidin-5-yl]piperazine-1-carboxylate
Synonyms	LP-935509 LP 935509 LP935509
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

ln Vitro	LP-935509 has an IC50 value of 2.8 ± 0.4 nM for μ2 phosphorylation inhibition and an IC50 value of 3.3 ± 0.7 nM for phosphorylation of peptides generated from μ2 protein[1]. The reduction of SARS-CoV-2 S-RBD internalization into host cells is demonstrated by LP-935509 in a dose-dependent manner [2].
ln Vivo	The oral single-dose medication LP-935509 (0–60 mg/kg) dramatically lowers pain behaviors [1]. ?In a CCI model, oral LP-935509 (0.1–30 mg/kg; single dosage) reverses thermal hyperalgesia in a dose-dependent manner [1]. ?LP-935509 (intravenous 1 mg/kg or oral 10 mg/kg once) has a 3.6-hour plasma half-life and 100% oral bioavailability [1].
Animal Protocol	Animal/Disease Models: Male C57BL/6J mice (with SNL (spinal nerve ligation) injury, n=8-10 male mice per group) [1] Doses: 0, 10, 30 and 60mg/kg (10ml/kg) Route of Administration: PO, Single Outcome: Produced a dose-dependent reduction in stage II paw withdrawal that was Dramatically lower than in vehicle-treated animals; demonstrated a dose-dependent reversal of mechanical allodynia; resulted in a substantial reduction in pain behaviors. Animal/Disease Models: Male SD (SD (Sprague-Dawley)) rat (CCI (chronic constriction injury) operated rat) [1] Doses: 0, 0.1, 0.3, 1, 3, 10 or 30 mg/kg Route of Administration: po (po (oral gavage)) daily Two, 5 consecutive day Experimental Results: Produced dose-dependent reversal of thermal hyperalgesia, cold hyperalgesia, mechanical hyperalgesia, and mechanical hyperalgesia in CCI animals. Reversal of behavioral deficits, ED50 values range from 2 mg/kg to 10 mg/kg. Animal/Disease Models: Male SD (SD (Sprague-Dawley)) rat[1] Doses: 1 mg/kg (IV), 10 mg/kg (PO) Route of Administration: IV, PO; once (pharmacokinetic/PK/PK analysis) Experimental Results: Oral bioavailability The conc
References	[1]. Inhibition of AAK1 Kinase as a Novel Therapeutic Approach to Treat Neuropathic Pain. J Pharmacol Exp Ther. 2016 Sep;358(3):371-86. [2]. Role Of Endocytic Machinery Regulators in EGFR Traffic and Viral Entry (2021). Theses & Dissertations. 532.

Solubility Data

Solubility (In Vitro)

DMSO : ~50 mg/mL (~126.12 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (5.25 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 20.8 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: ≥ 2.08 mg/mL (5.25 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 20.8 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. Solubility in Formulation 3: ≥ 2.08 mg/mL (5.25 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 20.8 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	2.5224 mL	12.6122 mL	25.2245 mL
	5 mM	0.5045 mL	2.5224 mL	5.0449 mL
	10 mM	0.2522 mL	1.2612 mL	2.5224 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.