[CAS NO. 1454555-29-3] LP-935509
PRODUCTS SPECIFICATIONS [1454555-29-3]
DESCRIPTION [1454555-29-3]
Overview
| MDL | - |
|---|---|
| Molecular Weight | 396.44 |
| Molecular Formula | C20H24N6O3 |
| SMILES | O=C(N1CCN(C2=NC3=C(C4=CC=CN=C4OC)C=NN3C=C2)CC1)OC(C)C |
Summary
LP-935509 is an orally active, potent, selective, ATP-competitive and brain-penetrant inhibitor of adaptor protein-2 associated kinase 1 (AAK1) with an IC 50 of 3.3 nM and a K i of 0.9 nM, respectively. LP-935509 is also a potent inhibitor of BIKE ( IC 50 =14 nM) and a modest inhibitor of GAK ( IC 50 =320 nM). LP-935509 shows antinociceptive activity. LP-935509 can be used for neuropathic pain and SARS-CoV-2 research [1] .
IC50 & Target
IC50: 3.3 ± 0.7 nM (AAK1), 14 nM (BIKE), 320 ± 40 nM (GAK) [1]
In Vitro
LP-935509 inhibits μ2 phosphorylation with an IC
50
value of 2.8 ± 0.4 nM, inhibits phosphorylation of a peptide derived from the μ2 protein with an IC
50
value of 3.3 ± 0.7 nM
[1]
.
LP-935509 exhibits a dose-dependent inhibition of the SARS-CoV-2 S-RBD internalization into host cells
[2]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
LP-935509 (0-60 mg/kg; PO, single) causes a robust reduction in pain behavior
[1]
.
LP-935509 (0.1-30 mg/kg; PO, single dosage) causes a dose-dependent reversal of thermal hyperalgesia in CCI model
[1]
.
LP-935509 (IV (1 mg/kg) or orally (10 mg/kg); once) has 100% oral bioavailability and a plasma half life of 3.6 hours
[1]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
| Animal Model: | Male C57BL/6J mice (with SNL(spinal nerve ligation) injury, n=8-10 male mice per group) [1] |
| Dosage: | 0, 10, 30 and 60 mg/kg (10 ml/kg) |
| Administration: | PO, single |
| Result: | Caused a dose-dependent reduction in phase II paw flinches that was significantly lower than the vehicle-treated animals; exhibited a dose-dependent reversal of the mechanical allodynia; Caused a robust reduction in pain behavior. |
| Animal Model: | Male Sprague-Dawley rats (CCI (chronic constriction injury)-operated rats) [1] |
| Dosage: | 0, 0.1, 0.3, 1, 3, 10, or 30 mg/kg |
| Administration: | PO, two daily, for 5 days |
| Result: | Caused a dose-dependent reversal of thermal hyperalgesia, cold allodynia, mechanical allodynia, and mechanical hyperalgesia in CCI animals. Reversed the behavioral deficits, with ED 50 values ranging from 2 mg/kg to 10 mg/kg. |
| Animal Model: | Male Sprague-Dawley rats [1] |
| Dosage: | 1 mg/kg (IV), 10 mg/kg (PO) |
| Administration: | IV, PO; once (Pharmacokinetic Analysis) |
| Result: | Had 100% oral bioavailability and a plasma half life of 3.6 hours; The Cmax for the 10 mg/kg oral dose was 5.2 µM at 0.5-hour postdose; had a plasma-free fraction of 2.6% in mice. Brain drug levels exceeded plasma drug levels with a brain/plasma drug ratio typically between 3 and 4, showing that LP-935509 was highly brain-penetrant. |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
| Powder | -20°C | 3 years |
|---|---|---|
| 4°C | 2 years | |
| In solvent | -80°C | 6 months |
| -20°C | 1 month |
Solvent & Solubility
DMSO : 50 mg/mL ( 126.12 mM ; Need ultrasonic)
Stock Solutions
| Concentration Solvent Mass | 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 |
References