1217457-86-7
1217457-86-7 structure
- Name: GGTI 298
- Chemical Name: GGTI 298 trifluoroacetate salt hydrate
- CAS Number: 1217457-86-7
- Molecular Formula: C29H34F3N3O5S
- Molecular Weight: 593.658
- Catalog: Signaling Pathways GPCR/G Protein Ras
- Create Date: 2016-01-09 12:00:00
- Modify Date: 2024-01-08 19:36:06
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GGTI298 Trifluoroacetate is a CAAZ peptidomimetic geranylgeranyltransferase I (GGTase I) inhibitor, which can inhibit Rap1A with IC50 of 3 μM; little effect on Ha-Ras with IC50 of >20 μM.
| Name | GGTI 298 trifluoroacetate salt hydrate |
|---|---|
| Synonyms |
Methyl N-[4-{[(2R)-2-amino-3-sulfanylpropyl]amino}-2-(1-naphthyl) benzoyl]-L-leucinate trifluoroacetate (1:1)
L-Leucine, N-[4-[[(2R)-2-amino-3-mercaptopropyl]amino]-2-(1-naphthalenyl)benzoyl]-, methyl ester, compd. with 2,2,2-trifluoroacetic acid (1:1) Methyl N-[4-{[(2R)-2-amino-3-sulfanylpropyl]amino}-2-(1-naphthyl)benzoyl]-L-leucinate trifluoroacetate (1:1) GGTI298 Trifluoroacetate |
| Description | GGTI298 Trifluoroacetate is a CAAZ peptidomimetic geranylgeranyltransferase I (GGTase I) inhibitor, which can inhibit Rap1A with IC50 of 3 μM; little effect on Ha-Ras with IC50 of >20 μM. |
|---|---|
| Related Catalog | |
| Target |
IC50: 3 μM (Rap1A, in vivo), > 20 μM (Ha-Ras, in vivo)[3] |
| In Vitro | RhoA inhibitor (GGTI298 Trifluoroacetate) significantly reduces cAMP agonist-stimulated apical K+ conductance[1]. Knockdown of DR4 abolishes NF-κB activation, leading to sensitization of DR5-dependent apoptosis induced by the combination of GGTI298 Trifluoroacetate and TRAIL. GGTI298 Trifluoroacetate/TRAIL activates NF-κB and inhibits Akt. Knockdown of DR5, prevents GGTI298/TRAIL-induced IκBα and p-Akt reduction, suggesting that DR5 mediates reduction of IκBα and p-Akt induced by GGTI298/TRAIL. In contrast, DR4 knockdown further facilitates GGTI298/TRAIL-induced p-Akt reduction[2]. |
| In Vivo | The vivo mouse ileal loop experiments show fluid accumulation is reduced in a dose-dependent manner by TRAM-34, GGTI298 Trifluoroacetate, or H1152 when inject together with cholera toxin into the loop[1]. |
| Kinase Assay | The given cells are lysed with reporter lysis buffer and subjected to luciferase activity assay using luciferase assay system in a luminometer. Relative luciferase activity is normalized to protein content[2]. |
| Cell Assay | Cells are seeded in 96-well cell culture plates and treated the next day with the agents (including GGTI298 Trifluoroacetate). The viable cell number is determined using the sulforhodamine B assay[2]. |
| Animal Admin | The ileal loop experiment is performed in 6-8-week-old mice by a modifing rabbit ileal loop assay. Following gut sterilization, the animals are kept fasted for 24 h prior to surgery and fed only water ad libitum. Anesthesia is induced by a mixture of ketamine (35 mg/kg of body weight) and xylazine (5 mg/kg of body weight). A laparotomy is performed, and the experimental loops of 5-cm length are constricted at the terminal ileum by tying with non-absorbable silk. The following fluids are instilled in each loop by means of a tuberculin syringe fitting with a disposable needle through the ligated end of the loop: pure CT (1 μg; positive control), saline (negative control), CT (1 μg)+TRAM-34 (different concentrations in μM), CT (1 μg)+ H1152 (1 μM), and CT (1 μg)+GGTI298 Trifluoroacetate (different concentrations in μM), a specific inhibitor of Rap1A. The intestine is returned to the peritoneum, and the mice are sutured and returned to their cages. After 6 h, these animals are sacrificed by cervical dislocation, and the loops are excised[1]. |
| References |
| Molecular Formula | C29H34F3N3O5S |
|---|---|
| Molecular Weight | 593.658 |
| Exact Mass | 593.217102 |
| PSA | 173.04000 |
| LogP | 6.47470 |
| Storage condition | -20℃ |