1088965-37-0
1088965-37-0 structure
- Name: GSK-923295
- Chemical Name: 3-chloro-N-[(2S)-1-[[2-(dimethylamino)acetyl]amino]-3-[4-[8-[(1S)-1-hydroxyethyl]imidazo[1,2-a]pyridin-2-yl]phenyl]propan-2-yl]-4-propan-2-yloxybenzamide
- CAS Number: 1088965-37-0
- Molecular Formula: C32H38ClN5O4
- Molecular Weight: 592.12800
- Catalog: Pharmaceutical intermediate Heterocyclic compound Pyridine compound Ethylpyridine
- Create Date: 2018-09-17 11:46:23
- Modify Date: 2024-01-14 23:22:02
-
GSK-923295 is a special, allosteric inhibitor of CENP-E kinesin motor ATPase activity, with Ki of 3.2±0.2 nM and 1.6± 0.1 nM for human and canine, respectively.
| Name | 3-chloro-N-[(2S)-1-[[2-(dimethylamino)acetyl]amino]-3-[4-[8-[(1S)-1-hydroxyethyl]imidazo[1,2-a]pyridin-2-yl]phenyl]propan-2-yl]-4-propan-2-yloxybenzamide |
|---|---|
| Synonyms |
3-chloro-N-{(1S)-2-[(N,N-dimethylglycyl)amino]-1-[(4-{8-[(1S)-1-hydroxyethyl]imidazo[1,2-a]pyridin-2-yl}phenyl)methyl]ethyl}-4-[(1-methylethyl)oxy]benzamide
3-Chloro-N-((S)-1-(2-(dimethylamino)acetamido)-3-(4-(8-((S)-1-hydroxyethyl)imidazo[1,2-a]pyridin-2-yl)phenyl)propan-2-yl)-4-isopropoxybenzamide GSK923295 GSK-923295 |
| Description | GSK-923295 is a special, allosteric inhibitor of CENP-E kinesin motor ATPase activity, with Ki of 3.2±0.2 nM and 1.6± 0.1 nM for human and canine, respectively. |
|---|---|
| Related Catalog | |
| Target |
CENP-E:1.6 nM (Ki, Canine CENP-E) |
| In Vitro | GSK-923295 (GSK923295) is a first-in-class, specific, allosteric inhibitor of CENP-E kinesin motor function. GSK923295 is uncompetitive with both ATP and MT, inhibiting CENP-E MT-stimulated ATPase activity with a Ki of 3.2±0.2 nM and 1.6±0.1 nM for human and canine, respectively. GSK923295 inhibits release of inorganic phosphate and stabilized CENP-E motor domain interaction with microtubules[1]. GSK923295 has broad growth inhibitory activity in a panel of 237 cancer cell lines and produces significant tumor growth-delay in 8 of the 11 mouse xenograft tumor models with IC50s of 17.2 nM, 55.6 nM, 42 nM, and 51.9 nM for SW48, RKO (BRAF mutant), SW620 (KRAS mutant), and HCT116 (KRAS mutant), respectively[2]. GSK923295 is a potent and selective small molecule inhibitor of human CENPE with a Ki of 3.2 nM. GSK923295 demonstrates broad efficacy against a panel of 19 human neuroblastoma derived cell lines with an average growth IC50 of 41 nM[3]. |
| In Vivo | Xenografts of mice treated with GSK-923295 (GSK923295) shows significant tumor growth delay compared to the control arm (NB-EBc1 p<0.0001; NB-1643 p=0.018; NB-1691 p=0.0018)[3]. |
| Cell Assay | Cell-growth inhibition assays are performed by MDS in 384-well plates, and DNA content of fixed cells stained with DAPI using an Incell 1000 (GE) is analyzed. DNA content is determined 24 h after seeding (T0) and after exposure to varying concentrations of GSK-923295 (0.01 nM, 0.1 nM, 1 nM, 10 nM, 100 nM, 1 μM, 10 μM, and 100 μM) for an additional 72 h (T72). All T72 measurements are normalized to T0. Curves are analyzed using the XLfit curve-fitting tool to determine the concentration of GSK923295 yielding 50% growth inhibition relative to T0 and Ymax values (GI50)[1]. |
| Animal Admin | Mice[3] CB17 scid mice are used to propagate subcutaneously implanted neuroblastoma tumors. Tumor diameters are measured using calipers. Tumor volumes are calculated. Once tumor volume exceeds 200 mm3, mice are randomized (n=10 per arm) to receive either GSK923295 125 mg/kg IP or vehicle (96% acidified water, 2% DMAC, 2% CREM) for a total of 6 doses using a 3 days on, 4 days off, 3 days on regimen. |
| References |
| Density | 1.25 |
|---|---|
| Melting Point | 197-198℃ |
| Molecular Formula | C32H38ClN5O4 |
| Molecular Weight | 592.12800 |
| Exact Mass | 591.26100 |
| PSA | 108.20000 |
| LogP | 5.29590 |
| Storage condition | -20℃ |
| Precursor 9 | |
|---|---|
| DownStream 0 | |
![N-((S)-1-AMINO-3-(4-(8-((S)-1-HYDROXYETHYL)IMIDAZO[1,2-A]PYRIDIN-2-YL)PHENYL)PROPAN-2-YL)-3-CHLORO-4-ISOPROPOXYBENZAMIDE structure](https://www.chemsrc.com/caspic/047/1240137-87-4.png)
