Synonym
GW779439X; GW 779439X; GW-779439X; NSC756341; NSC 756341; NSC-756341;
IUPAC/Chemical Name
N-[4-(4-Methylpiperazin-1-yl)-3-(trifluoromethyl)phenyl]-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amine
InChi Key
ZOTNSCLLJKXGSD-UHFFFAOYSA-N
InChi Code
InChI=1S/C22H21F3N8/c1-31-9-11-32(12-10-31)20-5-4-15(13-17(20)22(23,24)25)29-21-26-8-6-18(30-21)16-14-28-33-19(16)3-2-7-27-33/h2-8,13-14H,9-12H2,1H3,(H,26,29,30)
SMILES Code
FC(C1=CC(NC2=NC=CC(C3=C4C=CC=NN4N=C3)=N2)=CC=C1N5CCN(C)CC5)(F)F
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
>3 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
2934.99.03.00
Biological target:
GW779439X is a pyrazolopyridazine identified in an inhibitor of the S. aureus PASTA kinase Stk1. GW779439X potentiates the activity of β-lactam antibiotics against various MRSA and MSSA isolates, some even crossing the breakpoint from resistant to sensitive. GW779439X is an AURKA inhibitor and induces apoptosis by the caspases 3/7 pathway.
In vitro activity:
As can be seen in Table 1, GW779439X was able to potentiate the activity of all β-lactams tested, particularly the penicillinase-resistant penicillins oxacillin and nafcillin to an MIC considered susceptible to these agents.
Reference: ACS Infect Dis. 2018 Oct 12;4(10):1508-1518. https://pubmed.ncbi.nlm.nih.gov/30059625/
|
Solvent |
mg/mL |
mM |
Solubility |
DMSO |
31.3 |
68.76 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
454.46
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. Schaenzer AJ, Wlodarchak N, Drewry DH, Zuercher WJ, Rose WE, Ferrer CA, Sauer JD, Striker R. GW779439X and Its Pyrazolopyridazine Derivatives Inhibit the Serine/Threonine Kinase Stk1 and Act As Antibiotic Adjuvants against β-Lactam-Resistant Staphylococcus aureus. ACS Infect Dis. 2018 Oct 12;4(10):1508-1518. doi: 10.1021/acsinfecdis.8b00136. Epub 2018 Aug 15. PMID: 30059625; PMCID: PMC6779124.
In vitro protocol:
1. Schaenzer AJ, Wlodarchak N, Drewry DH, Zuercher WJ, Rose WE, Ferrer CA, Sauer JD, Striker R. GW779439X and Its Pyrazolopyridazine Derivatives Inhibit the Serine/Threonine Kinase Stk1 and Act As Antibiotic Adjuvants against β-Lactam-Resistant Staphylococcus aureus. ACS Infect Dis. 2018 Oct 12;4(10):1508-1518. doi: 10.1021/acsinfecdis.8b00136. Epub 2018 Aug 15. PMID: 30059625; PMCID: PMC6779124.
1: Retraction: Sophocleous, M. (2012). Conserving and extending the useful life of the largest aquifer in North America: The future of the High Plains/Ogallala aquifer. Ground Water , 50: 831–839. doi: 10.1111/j.1745-6584.2012.00965.x. Ground Water. 2014 Mar-Apr;52(2):323. doi: 10.1111/gwat.12189. PubMed PMID: 24754060.
2: Retraction: Sophocleous, M. (2012). On understanding and predicting groundwater response time. Ground Water, 50: 528–540. doi: 10.1111/j.1745-6584.2011.00876.x. Ground Water. 2014 Mar-Apr;52(2):322. doi: 10.1111/gwat.12188. PubMed PMID: 24754059.
3: Rausch R, Dirks H, Kallioras A, Schüth C. The riddle of the springs of Dilmun--does the Gilgamesh epic tell the truth? Ground Water. 2014 Jul-Aug;52(4):640-4. doi: 10.1111/gwat.12214. Epub 2014 Jun 4. PubMed PMID: 24898565.
4: Missimer T. Journal paper peer-review: a broken system? Ground Water. 2015 May-Jun;53(3):347. doi: 10.1111/gwat.12333. Epub 2015 Mar 27. PubMed PMID: 25818833.
5: Hu Y, Valocchi AJ, Lindgren SA, Ramos EA, Byrd RA. Groundwater Modeling with MODFLOW as a Web Application. Ground Water. 2015 Nov-Dec;53(6):834-5. doi: 10.1111/gwat.12372. Epub 2015 Sep 10. PubMed PMID: 26356870.
6: Lorenz WF, Wolfram EJ. The wells of Pompeii. Ground Water. 2014 Sep-Oct;52(5):808-11. doi: 10.1111/gwat.12221. Epub 2014 Jun 5. PubMed PMID: 24903069.
7: Ou G, Chen XH, Bitner RJ, Krausnick M. SMPP: The Spreadsheet-Based MODFLOW Pre-Processor. Ground Water. 2015 Sep-Oct;53(5):675-6. doi: 10.1111/gwat.12359. Epub 2015 Jul 24. PubMed PMID: 26212924.
8: Briskin J. Potential impacts of hydraulic fracturing for oil and gas on drinking water resources. Ground Water. 2015 Jan-Feb;53(1):19-21. PubMed PMID: 25713827.
9: Tammetta P. Estimation of the change in hydraulic conductivity above mined longwall panels. Ground Water. 2015 Jan-Feb;53(1):122-9. doi: 10.1111/gwat.12153. Epub 2014 Jan 9. PubMed PMID: 24405232.
10: Molz F. Advection, dispersion, and confusion. Ground Water. 2015 May-Jun;53(3):348-53. doi: 10.1111/gwat.12338. Epub 2015 Mar 27. PubMed PMID: 25819328.
11: Chapelle FH. The history and practice of peer review. Ground Water. 2014 Jan-Feb;52(1):1. doi: 10.1111/gwat.12139. Epub 2013 Nov 22. PubMed PMID: 24266884.
12: Hester CM, Coleman J. Between an uncomfortable decision and an absurd one. Ground Water. 2014 Sep-Oct;52(5):645-6. doi: 10.1111/gwat.12248. Epub 2014 Aug 20. PubMed PMID: 25141994.
13: Pauw PS, Van der Zee SE, Leijnse A, Delsman JR, De Louw PG, De Lange WJ, Oude Essink GH. Low-Resolution Modeling of Dense Drainage Networks in Confining Layers. Ground Water. 2015 Sep-Oct;53(5):771-81. doi: 10.1111/gwat.12273. Epub 2014 Sep 23. PubMed PMID: 25250661.
14: Haitjema HM, Anderson MP. Darcy Velocity Is Not a Velocity. Ground Water. 2016 Jan;54(1):1. doi: 10.1111/gwat.12386. Epub 2015 Nov 30. PubMed PMID: 26619221.
15: Bakker M. Python scripting: the return to programming. Ground Water. 2014 Nov-Dec;52(6):821-2. doi: 10.1111/gwat.12269. Epub 2014 Sep 16. PubMed PMID: 25227404.
16: Flewelling SA, Sharma M. "Constraints on upward migration of hydraulic fracturing fluid and brine," by S. A. Flewelling and M. Sharma. Ground Water. 2014 Jul-Aug;52(4):492-4. doi: 10.1111/gwat.12226. Epub 2014 Jun 27. PubMed PMID: 24976181.
17: Cook PG. The role of tracers in hydrogeology. Ground Water. 2015 Apr;53 Suppl 1:1-2. PubMed PMID: 26034796.
18: Haitjema H. How to get published in groundwater. Ground Water. 2015 Jan-Feb;53(1):1. doi: 10.1111/gwat.12303. Epub 2014 Nov 12. PubMed PMID: 25393422.
19: Ye M, Rios JF, Shi L. A new ArcGIS-based software of uncertainty analysis for nitrate load estimation. Ground Water. 2014 Sep-Oct;52(5):649-50. doi: 10.1111/gwat.12247. Epub 2014 Aug 20. PubMed PMID: 25141919.
20: Haitjema HM. The cost of modeling. Ground Water. 2015 Mar-Apr;53(2):179. doi: 10.1111/gwat.12321. Epub 2015 Jan 28. PubMed PMID: 25630760.