GSK3179106

SKU: orb1226027

Description

GSK3179106 (GSK-3179106, GSK 3179106) is a potent, selective, first-in-class and gut-restricted RET kinase inhibitor with IC50 of 0.4 and 11 nM in the biochemical assay and cellular assay respectively, 273-fold selectivity over KDR; possesses good kinase selectivity, only 26 out of a set of >300 recombinant kinases were found to be inhibited at 1 uM; GSK3179106 dosed orally at 10 mg/kg for 3.5 days BID reduced the visceromotor response to colorectal distension in comparison to rats given an acetic acid enema and dosed with vehicle, GSK3179106 has been developed for the treatment of IBS in a clinical setting.Irritable Bowel Syndrome,Phase 1 Clinical(In Vitro):GSK3179106 (10 nM-100 μM; 8 days for TT cells, 3 days for SK-N-AS and A549 cells) inhibits the proliferation of the RET-dependent TT cell line with a mean IC50 value of 25.5 nM however has no effect on the proliferation of the RET-independent SK-NAS and A549 cell lines (mean IC50>10 μM and IC30>17 μM, respectively).GSK3179106 inhibits RET phosphorylation in SK-N-AS cells and TT cells with mean IC50s of 4.6 nM and 11.1 nM, respectively.(In Vivo):GSK3179106 (3 or 10 mg/kg; orally; for 3.5 days BID) reduces the visceromotor response (VMR) in comparison to rats given an acetic acid enema and dosed with vehicle.

Key Properties

• CAS Number: 1627856-64-7
• MW: 467.421
• Purity: >98% (HPLC)
• Formula: C₂₂H₂₁F₄N₃O₄
• SMILES: O=C(NC1=NOC(C(C)(C)C(F)(F)F)=C1)CC2=CC=C(C(C(OCC)=C3)=CNC3=O)C=C2F
• Target: c-RET
• Solubility: DMSO : ≥ 100 mg/mL 213.94 mM

Bioactivity

• In Vivo:
  GSK3179106 (3 or 10 mg/kg; orally; for 3.5 days BID) reduces the visceromotor response (VMR) in comparison to rats given an acetic acid enema and dosed with vehicle. Animal model: Seventy male Sprague Dawley rats (225-250 g, ~7-8 weeks old); Fifty male Fischer 344 rats (225-250 g, ~10-12 weeks old); Sprague Dawley female rats. Dosage: 3 and 10 mg/kg. Administration: Oral gavage; administered BID at 8: 00 and 16: 00 for 3.5 days. Result: Reduced the visceral motor response. Led to a 34-43% inhibition in VMR to colorectal distension (CRD) at 10 mg/kg.
• In Vitro:
  GSK3179106 (10 nM-100 μM; 8 days for TT cells, 3 days for SK-N-AS and A549 cells) inhibits the proliferation of the RET-dependent TT cell line with a mean IC50 value of 25.5 nM however has no effect on the proliferation of the RET-independent SK-NAS and A549 cell lines (mean IC50>10 μM and IC30>17 μM, respectively). GSK3179106 inhibits RET phosphorylation in SK-N-AS cells and TT cells with mean IC50s of 4.6 nM and 11.1 nM, respectively. Cell Viability Assay Cell line: TT, SK-N-AS and A549 cells. Concentration: 10 nM-100 μM. Incubation time: 8 days for TT cells, 3 days for SK-N-AS and A549 cells. Result: Inhibited the proliferation of TT cell line with a mean IC50 value of 25.5 nM however had no effect on the proliferation of the SK-NAS and A549 cell lines (mean IC50>10 μM and IC30>17 μM, respectively).

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

GSK 3179106 | GSK-3179106

Quick Database Links

Gene Symbol

c-RET