aak1 (ap2 associated kinase 1)

AAK1-IN-1 (example 123) is an AAK1 (adaptor associated kinase 1) inhibitor with an IC50 of 2.2 nM. AAK1-IN-1 can be used for neurodegenerative diseases research[1]. Adaptor associated kinase 1 (AAK1) is a member of the Arkl/Prkl family of serine/threonine kinases. AAKl mRNA exists in two splice forms termed short and long. The long form predominates and is highly expressed in brain and heart. AAKl is enriched in synaptosomal preparations and is co-localized with endocytic structures in cultured cells. AAKl modulates clatherin coated endocytosis, a process that is important in synaptic vesicle recycling and receptor-mediated endocytosis[1]. [1]. Guanglin Luo, et al. Biaryl kinase inhibitors. WO2015153720A1.

BMT-124110 is a selective AAK1 inhibitor (IC50: 0.9 nM) with antinociceptive activity. BMT-090605 inhibited BMP-2 induced protein kinase BIKE with IC50 of 17 nM. BMT-090605 inhibits cyclin G-associated kinase GAK with an IC50 of 99 nM.

LP-922761 is a potent, selective, and orally active AAK1 inhibitor with inhibitory effects on BMP-2 induced protein kinase (BIKE).

SGC-AAK1-1, a potent and selective inhibitor of AAK1 (AP2-associated kinase 1), has an IC50 of 270 nM and a Ki of 9 nM, and serves as a chemical probe.

LP-935509 is a selective, brain-permeable, small molecule competitive inhibitor of articulin-2-associated kinase 1 (AAK1) with an IC50 of 3.3 nM and a Ki of 0.9 nM. LP-935509 is a potent inhibitor of BIKE (IC50 of 14 nM) and a moderate inhibitor of GAK (IC50 of 320±40 nM).

HW161023 (compound) is an orally active inhibitor of AP2 associated protein kinase 1 (AAK1), exhibiting IC50 values of 5.4 nM for AAK1 and 11.9 μM for hERG. HW161023 can suppress pain response in a rat model of chronic sciatic nerve compression injury.

SGC-AAK1-1N is a potent and selective inhibitor of AAK1 (AP2 associated kinase 1), with an IC50 of 1.8 μM [1].

RSS0680 is a protein kinase degrader that degrades a variety of kinases and can be used to study diseases caused by kinase abnormalities.

BMS-901715 is an effective and selective inhibitor of adapter protein-2 associated kinase 1 (AAK1; IC50: 3.3 nM).

BMT-090605 is a potent, selective AAK1 inhibitor with an IC50 of 0.6 nM, and inhibits BMP-2-inducible protein kinase (BIKE) and Cyclin G-associated kinase (GAK) with IC50s of 45 and 60 nM, respectively[1]. BMT-090605 also exhibits antinociceptive activity.

AAK1/HDACs-IN-1 (Compound 12) is a dual inhibitor targeting AAK1 and HDACs, effectively inhibiting AAK1, HDAC1, and HDAC6, with IC50 values of 15.9, 148.6, and 5.2 nM, respectively. This compound also hinders SARS-CoV-2 infection by blocking the endocytosis of the ACE2-SARS-CoV-2 complex and the AP2M1-ACE2 interaction.

AAK1-IN-6 is an inhibitor of AP-2 associated protein kinase 1 (AAK1, IC50 = 12 nM) and exhibits antiviral activity against Dengue virus (DNEV2, EC50 = 0.24 μM) and Venezuelan equine encephalitis virus (VEEV, EC50 = 0.30 μM). AAK1-IN-6 is applicable in antiviral research.

SARS-CoV-2-IN-81 (compound 12e) is an effective AAK1 inhibitor with an IC50 value of 9.38 nM. It demonstrates antiviral activity against SARS-CoV-2 by reducing AAK1-induced phosphorylation of threonine 156 on AP2M1 and disrupting the direct interaction between AP2M1 and ACE2, ultimately inhibiting SARS-CoV-2 infection.

TIM-098a is a selective AAK1 inhibitor with an IC50 of 0.24 µM. It does not inhibit CaMKK isoforms. By inhibiting AAK1 kinase activity, TIM-098a disrupts AAK1-regulated endocytosis.

AAK1-IN-7 (Compound 16) is a dual inhibitor of AAK1 and GAK with EC50 values of 40 nM and 80 nM, respectively. This compound inhibits the phosphorylation of the AP2-µ2 subunit at the T156 position. However, it demonstrates only weak antiviral activity against RNA viruses.

AAK1-IN-9 (Compound 3) is an inhibitor of AAK1 (adaptor associated kinase 1) with an IC50 value of 10.92 nM, and it is applicable in the study of neurodegenerative diseases.

AAK1-IN-8 (Compound 18) is a broad-spectrum NAK inhibitor. It effectively inhibits AAK1 and GAK with EC50 values of 50 nM and 190 nM, respectively, and prevents the phosphorylation of the AP2-µ2 subunit at threonine 156 (T156).

AAK1-IN-10 (Compound 1-2) is an AAK1 inhibitor with significant enzymatic inhibition of AAK1 (IC50: 9.62 nM). Its primary mechanism involves inhibiting adaptor-associated kinase 1 (AAK1) activity. AAK1-IN-10 exhibits minimal cardiotoxicity (IC50 = 13.7 μM) and can be utilized in research for diabetic neuralgia and postherpetic neuralgia.

AAK1-IN-11 is an inhibitor of AAK1 (adaptor associated kinase 1) with an IC50 of 2 nM, and it exhibits antiviral activity.

dAurAB5 is a dual PROTAC degrader targeting Aurora-A (DC50= 8.8 nM) and Aurora-B (DC50= 6.1 nM). It induces the degradation of Aurora-A and Aurora-B, leading to reduced N-Myc levels and decreased viability of IMR32 neuroblastoma cells. Additionally, dAurAB5 downregulates the levels of AAK1, PTK2, GAK, and TTK. This compound is applicable in cancer research, including neuroblastoma.

BMS-911172 is an adaptor-associated kinase 1 (AAK1 kinase) inhibitor with an IC50 of 35 nM.

AAK1-IN-2 (compound (S)-31) is a potent, selective, and brain-penetrant Adaptor Protein 2-Associated Kinase 1 (AAK1) inhibitor (IC50 = 5.8 nM) used in neuropathic pain research [1].

AAK1-IN-3 is a quinoline analogue that can be used in the research of neuropathic pain. AAK1-IN-3 is a brain-penetrant inhibitor of adaptor protein 2-associated kinase 1 (AAK1) (IC 50 = 11 nM) [1].

AAK1-IN-4 is a potent and specific inhibitor of adaptor protein-2-associated kinase 1 (AAK1), capable of efficiently penetrating the central nervous system and exhibiting oral bioactivity. It has demonstrated a high degree of selectivity with an AAK1 inhibitory concentration (IC50) of 4.6 nM, a Filt dissociation constant (Ki) of 0.9 nM, and a cellular IC50 of 8.6 nM. AAK1-IN-4 holds promise as a valuable tool in the investigation of neuropathic pain [1].