HTH-01-015NUAK1 inhibitor,highly specific and selective CAS# 1613724-42-7 |
- WZ4003
Catalog No.:BCC4363
CAS No.:1214265-58-3
Quality Control & MSDS
Number of papers citing our products
Chemical structure
3D structure
| Cas No. | 1613724-42-7 | SDF | Download SDF |
| PubChem ID | 78357766 | Appearance | Powder |
| Formula | C26H28N8O | M.Wt | 468.55 |
| Type of Compound | N/A | Storage | Desiccate at -20°C |
| Solubility | DMSO : 100 mg/mL (213.42 mM; Need ultrasonic) | ||
| SMILES | CC1=C2C(=NC(=N1)NC3=CN(N=C3)C4CCNCC4)N(C5=CC6=CC=CC=C6C=C5C(=O)N2C)C | ||
| Standard InChIKey | CHSDJDLAKKAWCI-UHFFFAOYSA-N | ||
| Standard InChI | InChI=1S/C26H28N8O/c1-16-23-24(31-26(29-16)30-19-14-28-34(15-19)20-8-10-27-11-9-20)32(2)22-13-18-7-5-4-6-17(18)12-21(22)25(35)33(23)3/h4-7,12-15,20,27H,8-11H2,1-3H3,(H,29,30,31) | ||
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it. |
||
| About Packaging | 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment. |
||
| Shipping Condition | Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request. | ||
| Description | Potent and selective NUAK1 inhibitor (IC50 = 100 nM). Exhibits no significant inhibition against a panel of 139 kinases, including ten AMPK family members. Inhibits NUAK1-mediated MYPT1 phosphorylation. Also inhibits cell proliferation in U2OS cells in vitro, to a similar extent as NUAK1 knockdown models. |
| Kinase experiment [1]: | |
| 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]: | |
| Cell lines | HEK293, MEFs and U2OS |
| Preparation method | Limited solubility. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
| Reacting condition | 37oC |
| 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. |
| 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. | |
HTH-01-015 Dilution Calculator
HTH-01-015 Molarity Calculator
| 1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
| 1 mM | 2.1342 mL | 10.6712 mL | 21.3424 mL | 42.6849 mL | 53.3561 mL |
| 5 mM | 0.4268 mL | 2.1342 mL | 4.2685 mL | 8.537 mL | 10.6712 mL |
| 10 mM | 0.2134 mL | 1.0671 mL | 2.1342 mL | 4.2685 mL | 5.3356 mL |
| 50 mM | 0.0427 mL | 0.2134 mL | 0.4268 mL | 0.8537 mL | 1.0671 mL |
| 100 mM | 0.0213 mL | 0.1067 mL | 0.2134 mL | 0.4268 mL | 0.5336 mL |
| * Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations. | |||||
Calcutta University
University of Minnesota
University of Maryland School of Medicine
University of Illinois at Chicago
The Ohio State University
University of Zurich
Harvard University
Colorado State University
Auburn University
Yale University
Worcester Polytechnic Institute
Washington State University
Stanford University
University of Leipzig
Universidade da Beira Interior
The Institute of Cancer Research
Heidelberg University
University of Amsterdam
University of Auckland
TsingHua University
The University of Michigan
Miami University
DRURY University
Jilin University
Fudan University
Wuhan University
Sun Yat-sen University
Universite de Paris
Deemed University
Auckland University
The University of Tokyo
Korea University
HTH-01-015 is a highly specific inhibitor of NUAK1 with IC50 value of 100 nM 1.
HTH-01-015 showed extreme selectivity. It only inhibited the NUAK1 (NUAK family SNF1-like kinase-1) isoform of NUAK kinases and showed no significant inhibition of 139 other tested kinases. HTH-01-015 inhibited the phosphorylation of the NUAK1 substrate, MYPT1. The phosphorylated site was identified as Ser445. In HEK cells overexpressing drug-resistant NUAK1, HTH-01-015 displayed no more inhibition effect on MYPT1. In MEF cells, HTH-01-015 markedly reduced cell migration in the wound-healing assay. Besides that, HTH-01-015 impaired the proliferation at concentration of 10 μM both in U2OS cells and in MEF cells. Moreover, 10 μM HTH-01-015 also significantly inhibited the invasiveness of U2OS cells in a 3D matrigel transwell invasion assay 1.
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.
- SGC-CBP30
Catalog No.:BCC2419
CAS No.:1613695-14-9
- Fmoc-Chg-OH
Catalog No.:BCC3164
CAS No.:161321-36-4
- 1-O-Acetyl-6-O-isobutyrylbritannilactone
Catalog No.:BCN7795
CAS No.:1613152-34-3
- SR-9243
Catalog No.:BCC3983
CAS No.:1613028-81-1
- H-Orn(Z)-OtBu.HCl
Catalog No.:BCC2677
CAS No.:161234-80-6
- Cimicidanol 3-O-alpha-L-arabinoside
Catalog No.:BCN6528
CAS No.:161207-05-2
- H-Asp(OEt)-OEt.HCl
Catalog No.:BCC2888
CAS No.:16115-68-7
- Bidwillol A
Catalog No.:BCN4858
CAS No.:161099-42-9
- Cimicifugoside H2
Catalog No.:BCN7949
CAS No.:161097-77-4
- Formyl-DL-Trp-OH
Catalog No.:BCC3120
CAS No.:16108-03-5
- Epimedokoreanin C
Catalog No.:BCN8080
CAS No.:161068-54-8
- Epimedokoreanin B
Catalog No.:BCN6483
CAS No.:161068-53-7
- ABT
Catalog No.:BCC7998
CAS No.:1614-12-6
- SIN-1 chloride
Catalog No.:BCC5670
CAS No.:16142-27-1
- 7-NINA
Catalog No.:BCC5674
CAS No.:161467-34-1
- 4-Chlorocinnamic acid
Catalog No.:BCN5032
CAS No.:1615-02-7
- Simiarenol
Catalog No.:BCN1714
CAS No.:1615-94-7
- Fmoc-Alaninol
Catalog No.:BCC2729
CAS No.:161529-13-1
- Cyclo (-RGDfK)
Catalog No.:BCC3590
CAS No.:161552-03-0
- Ro 48-8071
Catalog No.:BCC5545
CAS No.:161582-11-2
- (S)-N-Glycidylphthalimide
Catalog No.:BCN3815
CAS No.:161596-47-0
- 2'',3''-Di-O-acetyl-5''-deoxy-5-fuluro-D-cytidine
Catalog No.:BCN1545
CAS No.:161599-46-8
- beta-Amyrin acetate
Catalog No.:BCN1715
CAS No.:1616-93-9
- ZK 200775
Catalog No.:BCC7339
CAS No.:161605-73-8
Characterization of WZ4003 and HTH-01-015 as selective inhibitors of the LKB1-tumour-suppressor-activated NUAK kinases.[Pubmed:24171924]
Biochem J. 2014 Jan 1;457(1):215-25.
The related NUAK1 and NUAK2 are members of the AMPK (AMP-activated protein kinase) family of protein kinases that are activated by the LKB1 (liver kinase B1) tumour suppressor kinase. Recent work suggests they play important roles in regulating key biological processes including Myc-driven tumorigenesis, senescence, cell adhesion and neuronal polarity. In the present paper we describe the first highly specific protein kinase inhibitors of NUAK kinases namely WZ4003 and HTH-01-015. WZ4003 inhibits both NUAK isoforms (IC50 for NUAK1 is 20 nM and for NUAK2 is 100 nM), whereas HTH-01-015 inhibits only NUAK1 (IC50 is 100 nM). These compounds display extreme selectivity and do not significantly inhibit the activity of 139 other kinases that were tested including ten AMPK family members. In all cell lines tested, WZ4003 and HTH-01-015 inhibit the phosphorylation of the only well-characterized substrate, MYPT1 (myosin phosphate-targeting subunit 1) that is phosphorylated by NUAK1 at Ser(445). We also identify a mutation (A195T) that does not affect basal NUAK1 activity, but renders it ~50-fold resistant to both WZ4003 and HTH-01-015. Consistent with NUAK1 mediating the phosphorylation of MYPT1 we find that in cells overexpressing drug-resistant NUAK1[A195T], but not wild-type NUAK1, phosphorylation of MYPT1 at Ser(445) is no longer suppressed by WZ4003 or HTH-01-015. We also demonstrate that administration of WZ4003 and HTH-01-015 to MEFs (mouse embryonic fibroblasts) significantly inhibits migration in a wound-healing assay to a similar extent as NUAK1-knockout. WZ4003 and HTH-01-015 also inhibit proliferation of MEFs to the same extent as NUAK1 knockout and U2OS cells to the same extent as NUAK1 shRNA knockdown. We find that WZ4003 and HTH-01-015 impaired the invasive potential of U2OS cells in a 3D cell invasion assay to the same extent as NUAK1 knockdown. The results of the present study indicate that WZ4003 and HTH-01-015 will serve as useful chemical probes to delineate the biological roles of the NUAK kinases.
