1613724-42-7

Basic information

• Product Name: HTH-01-015
• Synonyms: HTH-01-015;5,13-Dihydro-4,5,13-trimethyl-2-[[1-(4-piperidinyl)-1H-pyrazol-4-yl]amino]-6H-naphtho[2,3-e]pyrimido[5,4-b][1,4]diazepin-6-one
• CAS NO: 1613724-42-7
• Molecular Formula: C26H28N8O
• Molecular Weight: 468.55352
• Product Categories: Inhibitors
• Mol File: 1613724-42-7.mol
• Article Data: 0

Chemical Properties

• Boiling Point: 759.6±70.0 °C(Predicted)
• Appearance: /
• Density: 1.41±0.1 g/cm3(Predicted)
• Storage Temp.: -20°C
• Solubility: ≥23.45 mg/mL in DMSO; insoluble in H2O; ≥14.67 mg/mL in EtOH with ultrasonic
• PKA: 9.84±0.10(Predicted)
• CAS DataBase Reference: HTH-01-015(CAS DataBase Reference)
• NIST Chemistry Reference: HTH-01-015(1613724-42-7)
• EPA Substance Registry System: HTH-01-015(1613724-42-7)

Safety Data

• Hazardous Substances Data: 1613724-42-7(Hazardous Substances Data)

Usage

Description

HTH-01-015 is a selective and potent inhibitor of the protein kinase NUAK1, with an IC50 value of 100 nM. It specifically targets the NUAK1 phosphorylation of myosin phosphate-targeting subunit 1 (MYPT1) substrate without affecting the activity of 139 other kinases, including additional AMPK family members. NUAK1 is a member of the AMP-activated protein kinase (AMPK) family and is involved in various cellular processes such as cell adhesion, cancer cell invasion, embryonic development, senescence, proliferation, neuronal polarity, and axon branching.

Uses

Used in Cancer Research:
HTH-01-015 is used as a research tool for studying the role of NUAK1 in cancer cell invasion and proliferation. By inhibiting the phosphorylation of MYPT1 substrate, it helps researchers understand the underlying mechanisms of cancer progression and the potential therapeutic applications of targeting NUAK1 in cancer treatment.
Used in Cell Proliferation and Migration Studies:
HTH-01-015 is used as a compound to inhibit cell proliferation and migration in in vitro assays, such as wound-healing assays. At a concentration of 10 μM, it has been shown to inhibit the proliferation and migration of mouse embryonic fibroblasts.
Used in Cell Invasion Assays:
HTH-01-015 is used as an inhibitor to impair the invasive potential of cancer cells, such as U2OS cells, in 3D cell invasion assays at similar concentrations (10 μM). This application helps researchers investigate the role of NUAK1 in cancer cell invasion and the effectiveness of HTH-01-015 in preventing or reducing invasive behavior.
Used in Drug Development:
HTH-01-015 serves as a starting point for the development of novel therapeutics targeting NUAK1 in various diseases, including cancer. Its high specificity and potency make it a valuable candidate for further optimization and development into a potential drug for treating cancer and other conditions related to NUAK1 dysregulation.

Biochem/physiol Actions

HTH-01-015 is a potent and selective inhibitor of NUAK1 kinase, a member of the AMPK family that are that are activated by the LKB1 (liver kinaseB1) tumour suppressor kinase and involved in development and proliferation. HTH-01-015 has an IC50 of 100 nM for NUAK1, >100-fold higher than NUAK2, and has no significant inhibition of 139 other kinases tested, including ten AMPK-related kinase family members. Treatment with HTH-01-015 was found to suppress proliferation, restricting cells from entering into mitosis.

references

1. sourav b, sara j b, hai-tsang h, et al. characterization of wz4003 and hth-01-015 as selective inhibitors of the lkb1-tumour-suppressor-activated nuak kinases. biochemical journal, 2014, 457(1): 215-225.