LP-935509 | CAS# 1454555-29-3 | AAK1 Inhibitor

MedKoo Cat#: 564790 | Name: LP-935509

Description:

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

LP-935509 is a potent inhibitor of the Adapter protein-2 Associated Kinase 1 (AAK1). LP-935509, caused a reduced pain response in phase II formalin and reversed fully established pain behavior following the SNL procedure. LP-935509 also reduced evoked pain responses in the rat chronic constriction injury (CCI) model and the rat streptozotocin model of diabetic peripheral neuropathy.

Chemical Structure

LP-935509

CAS#1454555-29-3

Theoretical Analysis

MedKoo Cat#: 564790

Name: LP-935509

CAS#: 1454555-29-3

Chemical Formula: C20H24N6O3

Exact Mass: 396.1910

Molecular Weight: 396.45

Elemental Analysis: C, 60.59; H, 6.10; N, 21.20; O, 12.11

Price and Availability

Size	Price	Availability
50mg	USD 550.00	2 Weeks
100mg	USD 950.00	2 Weeks
200mg	USD 1,450.00	2 Weeks
500mg	USD 2,950.00	2 Weeks
1g	USD 4,250.00	2 Weeks
2g	USD 6,850.00	2 Weeks

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Related CAS #

1454555-29-3

Synonym

LP935509; LP 935509; LP-935509

IUPAC/Chemical Name

4-[3-(2-Methoxy-pyridin-3-yl)-pyrazolo[1,5-a]pyrimidin-5-yl]-piperazine-1-carboxylic acid isopropyl ester

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

SMILES Code

O=C(N1CCN(C2=NC3=C(C4=CC=CN=C4OC)C=NN3C=C2)CC1)OC(C)C

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

Shelf Life

>3 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

AAK1 inhibitors are a novel therapeutic approach to neuropathic pain with activity in animal models that is mechanistically linked (behaviorally and electrophysiologically) to α2 adrenergic signaling, a pathway known to be antinociceptive in humans.

Product Data

Product Data

Instruction

View handling instruction

Biological target:

LP-935509 is an orally active, potent, selective, ATP-competitive and brain-penetrant inhibitor of adaptor protein-2 associated kinase 1 (AAK1) with an IC50 of 3.3 nM and a Ki of 0.9 nM, respectively. LP-935509 is also a potent inhibitor of BIKE (IC50=14 nM) and a modest inhibitor of GAK (IC50=320 nM).

In vitro activity:

To test the activity of LP-935509 in an intact cellular system, the compound was incubated with HEK293 cells overexpressing human AAK1 and the human μ2 protein. These studies showed that LP-935509 inhibited μ2 phosphorylation with an IC50 value of 2.8 ± 0.4 nM (n = 26) (Supplemental Fig. 1B; Table 1). Reference: J Pharmacol Exp Ther. 2016 Sep;358(3):371-86. https://pubmed.ncbi.nlm.nih.gov/27411717/

In vivo activity:

The effect of LP-935509 on antinociception was further explored in rats because this species is commonly used to evaluate novel antinociceptive agents. In CCI animals, oral LP-935509 caused a dose-dependent reversal of thermal hyperalgesia (Fig. 6A), cold allodynia (Fig. 6B), mechanical allodynia (Fig. 6C), and mechanical hyperalgesia (Fig. 6D). In particular, LP-935509 completely reversed thermal hyperalgesia and mechanical allodynia at 10 and 30 mg/kg, with most assays showing significant antinociceptive activity at lower doses (ranging from 0.3 mg/kg to 3 mg/kg). Reference: J Pharmacol Exp Ther. 2016 Sep;358(3):371-86. https://pubmed.ncbi.nlm.nih.gov/27411717/

	Solvent	mg/mL	mM	comments
Solubility
	DMSO	50.0	126.12

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 396.45 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. Kostich W, Hamman BD, Li YW, Naidu S, Dandapani K, Feng J, Easton A, Bourin C, Baker K, Allen J, Savelieva K, Louis JV, Dokania M, Elavazhagan S, Vattikundala P, Sharma V, Das ML, Shankar G, Kumar A, Holenarsipur VK, Gulianello M, Molski T, Brown JM, Lewis M, Huang Y, Lu Y, Pieschl R, O'Malley K, Lippy J, Nouraldeen A, Lanthorn TH, Ye G, Wilson A, Balakrishnan A, Denton R, Grace JE, Lentz KA, Santone KS, Bi Y, Main A, Swaffield J, Carson K, Mandlekar S, Vikramadithyan RK, Nara SJ, Dzierba C, Bronson J, Macor JE, Zaczek R, Westphal R, Kiss L, Bristow L, Conway CM, Zambrowicz B, Albright CF. Inhibition of AAK1 Kinase as a Novel Therapeutic Approach to Treat Neuropathic Pain. J Pharmacol Exp Ther. 2016 Sep;358(3):371-86. doi: 10.1124/jpet.116.235333. Epub 2016 Jul 13. PMID: 27411717; PMCID: PMC4998676.

In vitro protocol:

In vivo protocol:

1: Louis JV, Lu Y, Pieschl R, Tian Y, Hong Y, Dandapani K, Naidu S, Vikramadithyan RK, Dzierba C, Sarvasiddhi SK, Nara SJ, Bronson J, Macor JE, Albright C, Kostich W, Li YW. [(3)H]BMT-046091 a potent and selective radioligand to determine AAK1 distribution and target engagement. Neuropharmacology. 2017 May 15;118:167-174. doi: 10.1016/j.neuropharm.2017.03.015. Epub 2017 Mar 15. PubMed PMID: 28315351. 2: Kostich W, Hamman BD, Li YW, Naidu S, Dandapani K, Feng J, Easton A, Bourin C, Baker K, Allen J, Savelieva K, Louis JV, Dokania M, Elavazhagan S, Vattikundala P, Sharma V, Das ML, Shankar G, Kumar A, Holenarsipur VK, Gulianello M, Molski T, Brown JM, Lewis M, Huang Y, Lu Y, Pieschl R, O'Malley K, Lippy J, Nouraldeen A, Lanthorn TH, Ye G, Wilson A, Balakrishnan A, Denton R, Grace JE, Lentz KA, Santone KS, Bi Y, Main A, Swaffield J, Carson K, Mandlekar S, Vikramadithyan RK, Nara SJ, Dzierba C, Bronson J, Macor JE, Zaczek R, Westphal R, Kiss L, Bristow L, Conway CM, Zambrowicz B, Albright CF. Inhibition of AAK1 Kinase as a Novel Therapeutic Approach to Treat Neuropathic Pain. J Pharmacol Exp Ther. 2016 Sep;358(3):371-86. doi: 10.1124/jpet.116.235333. Epub 2016 Jul 13. PubMed PMID: 27411717; PubMed Central PMCID: PMC4998676.