WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 406831
CAS#: 1214265-58-3
Description: WZ4003 is a selective inhibitors of the LKB1-tumour-suppressor-activated NUAK kinases. WZ4003 inhibits both NUAK isoforms (IC50 for NUAK1 is 20 nM and for NUAK2 is 100 nM). WZ4003 displays 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 inhibits the phosphorylation of the only well-characterized substrate, MYPT1 (myosin phosphate-targeting subunit 1) that is phosphorylated by NUAK1 at Ser(445).
MedKoo Cat#: 406831
Name: WZ4003
CAS#: 1214265-58-3
Chemical Formula: C25H29ClN6O3
Exact Mass: 496.199
Molecular Weight: 496.996
Elemental Analysis: C, 60.42; H, 5.88; Cl, 7.13; N, 16.91; O, 9.66
Synonym: WZ4003; WZ-4003; WZ 4003.
IUPAC/Chemical Name: N-[3-[[5-chloro-2-[[2-methoxy-4-(4-methyl-1-piperazinyl)phenyl]amino]-4-pyrimidinyl]oxy]phenyl]-propanamide
InChi Key: SDGJBAUIGHSMRI-UHFFFAOYSA-N
InChi Code: InChI=1S/C25H29ClN6O3/c1-4-23(33)28-17-6-5-7-19(14-17)35-24-20(26)16-27-25(30-24)29-21-9-8-18(15-22(21)34-3)32-12-10-31(2)11-13-32/h5-9,14-16H,4,10-13H2,1-3H3,(H,28,33)(H,27,29,30)
SMILES Code: CCC(NC1=CC=CC(OC2=NC(NC3=CC=C(N4CCN(C)CC4)C=C3OC)=NC=C2Cl)=C1)=O
Appearance: White to beige 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: >2 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
| Biological target: | WZ4003 is a NUAK kinase inhibitor with IC50 of 20 nM/100 nM for NUAK1 (ARK5)/NUAK2. |
| In vitro activity: | The structure of WZ4003 is shown in Figure 1(A). It inhibits NUAK1 with an IC50 of 20 nM (Figure 1B) and NUAK2 with an IC50 of 100 nM (Figure 1B). To evaluate the specificity of WZ4003 this study studied the effect that this compound has on the activity of 140 protein kinases, including ten AMPK-related kinase family members most closely related to NUAK1 (Figure 1C and Supplementary Table S1). WZ4003 was remarkably specific and, apart from NUAK1 and NUAK2, did not significantly inhibit ten other AMPK-related kinases or other kinases tested, including LKB1 at a concentration of 1 μM (10-fold higher than the IC50 of inhibition of NUAK1). Reference: Biochem J. 2014 Jan 1; 457(Pt 1): 215–225. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3969223/ |
| In vivo activity: | N/A |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 16.07 | 32.33 | |
| DMF | 14.0 | 28.17 | |
| DMF:PBS (pH 7.2) (1:1) | 0.5 | 1.01 |
The following data is based on the product molecular weight 496.996 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. Banerjee S, Buhrlage SJ, Huang HT, Deng X, Zhou W, Wang J, Traynor R, Prescott AR, Alessi DR, Gray NS. Characterization of WZ4003 and HTH-01-015 as selective inhibitors of the LKB1-tumour-suppressor-activated NUAK kinases. Biochem J. 2014 Jan 1;457(1):215-25. doi: 10.1042/BJ20131152. PMID: 24171924; PMCID: PMC3969223. |
| In vitro protocol: | 1. Banerjee S, Buhrlage SJ, Huang HT, Deng X, Zhou W, Wang J, Traynor R, Prescott AR, Alessi DR, Gray NS. Characterization of WZ4003 and HTH-01-015 as selective inhibitors of the LKB1-tumour-suppressor-activated NUAK kinases. Biochem J. 2014 Jan 1;457(1):215-25. doi: 10.1042/BJ20131152. PMID: 24171924; PMCID: PMC3969223. |
| In vivo protocol: | N/A |
1: Banerjee S, Zagórska A, Deak M, Campbell DG, Prescott AR, Alessi DR. Interplay between Polo kinase, LKB1-activated NUAK1 kinase, PP1βMYPT1 phosphatase complex and the SCFβTrCP E3 ubiquitin ligase. Biochem J. 2014 Jul 15;461(2):233-45. doi: 10.1042/BJ20140408. PubMed PMID: 24785407; PubMed Central PMCID: PMC4109838.
2: Banerjee S, Buhrlage SJ, Huang HT, Deng X, Zhou W, Wang J, Traynor R, Prescott AR, Alessi DR, Gray NS. Characterization of WZ4003 and HTH-01-015 as selective inhibitors of the LKB1-tumour-suppressor-activated NUAK kinases. Biochem J. 2014 Jan 1;457(1):215-25. doi: 10.1042/BJ20131152. PubMed PMID: 24171924; PubMed Central PMCID: PMC3969223.
