HTH-01-015
HTH-01-015 (CAS 1613724-42-7) is a highly selective inhibitor targeting the NUAK1 kinase, exhibiting potent inhibitory activity with an IC50 of approximately 100 nM. It specifically blocks NUAK1-mediated phosphorylation of MYPT1 at Ser445 with negligible off-target effects among a comprehensive panel of 139 other kinases. Cellular studies demonstrate that treatment with HTH-01-015 reduces migration of mouse embryonic fibroblasts (MEFs), suppresses proliferation in U2OS and MEF cell lines at concentrations around 10 μM, and significantly inhibits invasion of U2OS cells within 3D Matrigel transwell assays. This compound serves as a useful research tool for investigating NUAK1-related signaling pathways in cancer biology and cellular dynamics.
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 468.55 |
| Cas No. | 1613724-42-7 |
| Formula | C26H28N8O |
| Solubility | ≥23.45 mg/mL in DMSO; insoluble in H2O; ≥14.67 mg/mL in EtOH with ultrasonic |
| Chemical Name | 4,5,13-trimethyl-2-((1-(piperidin-4-yl)-1H-pyrazol-4-yl)amino)-5H-naphtho[2,3-e]pyrimido[5,4-b][1,4]diazepin-6(13H)-one |
| SDF | Download SDF |
| Canonical SMILES | CN1C(C2=CC3=CC=CC=C3C=C2N(C)C4=NC(NC5=CN(C6CCNCC6)N=C5)=NC(C)=C14)=O |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Kinase experiment [1]: | |
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Kinase activity assays |
In vitro activities of purified GST–NUAK1 and GST–NUAK1 [A195T] were measured using Cerenkov counting of incorporation of radioactive 32P from [γ -32P] ATP into Sakamototide substrate peptide. Reactions were carried out in a 50 μl reaction volume for 30 min at 30 μC and reactions were terminated by spotting 40 μl of the reaction mix on to P81 paper and immediately immersing in 50 mM orthophosphoric acid. Samples were washed three times in 50 mMorthophosphoric acid followed by a single acetone rinse and air drying. The kinase-mediated incorporation of [γ -32P] ATP into Sakamototide was quantified by Cerenkov counting. One unit of activity was defined as that which catalyzed the incorporation of 1 nmol of [32P]phosphate into the substrate over 1 h. |
| Cell experiment [1]: | |
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Cell lines |
HEK293, MEFs and U2OS |
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Preparation method |
Limited solubility. General tips for obtaining a higher concentration: Please warm the tube at 37°C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20°C for several months. |
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Reaction Conditions |
37°C |
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Applications |
In HEK-293 cells expressing wild-type NUAK1, 3–10 μM HTH-01-015 significantly inhibits phosphorylation of MYPT1. Treatment of NUAK1+/+ MEFs with 10 μM HTH-01-015 prominently suppresses cell migration in the wound-healing assay. In U2OS cells, HTH-01-015 blocks proliferation and phosphorylation of MYPT1 to the same extent as shRNA-mediated NUAK1 knockdown. |
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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. |
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| Description | HTH-01-015 is a selective inhibitor of NUAK1 kinase with an IC50 value of 100 nM. | |||||
| Targets | NUAK1 | |||||
| IC50 | 100 nM | |||||
Quality Control & MSDS
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Chemical structure
