Synonym
GNE-2861; GNE 2861; GNE2861.
IUPAC/Chemical Name
1-(2-(1-(2-aminopyrimidin-4-yl)-2-((2-methoxyethyl)amino)-1H-1,3-benzodiazol-6-yl)ethynyl)cyclohexan-1-ol
InChi Key
RZXMIHOUHYSGJO-UHFFFAOYSA-N
InChi Code
InChI=1S/C22H26N6O2/c1-30-14-13-25-21-26-17-6-5-16(7-11-22(29)9-3-2-4-10-22)15-18(17)28(21)19-8-12-24-20(23)27-19/h5-6,8,12,15,29H,2-4,9-10,13-14H2,1H3,(H,25,26)(H2,23,24,27)
SMILES Code
OC1(C#CC2=CC=C3N=C(NCCOC)N(C4=NC(N)=NC=C4)C3=C2)CCCCC1
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
More Info
Estrogen receptor alpha (ERα) is highly expressed in most breast cancers. Consequently, ERα modulators, such as tamoxifen, are successful in breast cancer treatment, although tamoxifen resistance is commonly observed. While tamoxifen resistance may be caused by altered ERα signaling, the molecular mechanisms regulating ERα signaling and tamoxifen resistance are not entirely clear
Biological target:
GNE 2861 inhibits PAK4, PAK5 and PAK6 with IC50s of 7.5, 36, 126 nM, respectively.
In vitro activity:
GNE-2861 enhanced the tamoxifen sensitivity in MCF-7 cells (Figure 2B), as well as in the tamoxifen-resistant human breast cancer cell line MCF-7/LCC2 where GNE-2861 restored the tamoxifen sensitivity to a similar level as in untreated tamoxifen-sensitive MCF-7 maternal cells (Figure 2B–2C). As shown in Figure 2B–2C, the approximate IC50 of tamoxifen in MCF-7/Control and MCF7/LCC2 cells are 7 μM and 14 μM, respectively. By keeping the tamoxifen concentration constant at the approximate IC50 for each cell line and varying the concentration of GNE-2861, it was found that tamoxifen sensitized breast cancer cells to GNE-2861 treatment (Figure 2D–2E). Together, this indicates that PAK4 contributes to tamoxifen resistance in breast cancer cells and may be used as a target to restore tamoxifen sensitivity. Further, this indicates that the group II PAK inhibitor GNE-2861 may be a candidate for the development of tamoxifen-sensitizing pharmacological treatment.
Reference: Oncotarget. 2015 Dec 22;6(41):43853-68. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4791272/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
82.8 |
203.77 |
| Ethanol |
40.7 |
100.00 |
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
406.49
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. Zhuang T, Zhu J, Li Z, Lorent J, Zhao C, Dahlman-Wright K, Strömblad S. p21-activated kinase group II small compound inhibitor GNE-2861 perturbs estrogen receptor alpha signaling and restores tamoxifen-sensitivity in breast cancer cells. Oncotarget. 2015 Dec 22;6(41):43853-68. doi: 10.18632/oncotarget.6081. PMID: 26554417; PMCID: PMC4791272.
In vitro protocol:
1. Zhuang T, Zhu J, Li Z, Lorent J, Zhao C, Dahlman-Wright K, Strömblad S. p21-activated kinase group II small compound inhibitor GNE-2861 perturbs estrogen receptor alpha signaling and restores tamoxifen-sensitivity in breast cancer cells. Oncotarget. 2015 Dec 22;6(41):43853-68. doi: 10.18632/oncotarget.6081. PMID: 26554417; PMCID: PMC4791272.
1: Zhuang T, Zhu J, Li Z, Lorent J, Zhao C, Dahlman-Wright K, Strömblad S.
p21-activated kinase group II small compound inhibitor GNE-2861 perturbs estrogen
receptor alpha signaling and restores tamoxifen-sensitivity in breast cancer
cells. Oncotarget. 2015 Dec 22;6(41):43853-68. doi: 10.18632/oncotarget.6081.
PubMed PMID: 26554417; PubMed Central PMCID: PMC4791272.
2: Staben ST, Feng JA, Lyle K, Belvin M, Boggs J, Burch JD, Chua CC, Cui H,
DiPasquale AG, Friedman LS, Heise C, Koeppen H, Kotey A, Mintzer R, Oh A, Roberts
DA, Rouge L, Rudolph J, Tam C, Wang W, Xiao Y, Young A, Zhang Y, Hoeflich KP.
Back pocket flexibility provides group II p21-activated kinase (PAK) selectivity
for type I 1/2 kinase inhibitors. J Med Chem. 2014 Feb 13;57(3):1033-45. doi:
10.1021/jm401768t. Epub 2014 Feb 4. PubMed PMID: 24432870.
