RET Kinase inhibitor 1
RET Kinase inhibitor 1 Basic information
- Product Name:
- RET Kinase inhibitor 1
- Synonyms:
-
- CS-2597
- c-RET inhibitor GS3179106
- RET Kinase inhibitor 1
- GSK3179106
- GSK-3179106
- Benzeneacetamide, 4-(4-ethoxy-1,6-dihydro-6-oxo-3-pyridinyl)-2-fluoro-N-[5-(2,2,2-trifluoro-1,1-dimethylethyl)-3-isoxazolyl]-
- syndrome,post-inflammatory,visceral,stress-induced,irritable,RET,Inhibitor,bowel,hypersensitivity,orally,GSK 3179106,inhibit,IBS,GSK3179106,GSK-3179106
- G414201] GSK3179106
- CAS:
- 1627856-64-7
- MF:
- C22H21F4N3O4
- MW:
- 467.41
- Mol File:
- 1627856-64-7.mol
RET Kinase inhibitor 1 Chemical Properties
- Boiling point:
- 670.1±55.0 °C(Predicted)
- Density
- 1.37±0.1 g/cm3(Predicted)
- storage temp.
- 2-8°C
- solubility
- DMSO:81.0(Max Conc. mg/mL);173.29(Max Conc. mM)
DMSO:PBS (pH 7.2) (1:3):0.25(Max Conc. mg/mL);0.53(Max Conc. mM)
Ethanol:15.5(Max Conc. mg/mL);33.16(Max Conc. mM) - form
- A crystalline solid
- pka
- 10.30±0.10(Predicted)
- color
- White to off-white
RET Kinase inhibitor 1 Usage And Synthesis
Description
GSK3179106 is an inhibitor of rearranged during transfection (RET) kinase (IC50 = 0.4 nM). It is selective for RET kinase over VEGF receptor 2 (VEGFR2/KDR; IC50 = 109 nM). GSK3179106 reduces the number of abdominal contractions induced by colorectal distension in acetic acid-sensitized rats when administered at a dose of 10 mg/kg twice per day.
Uses
GSK3179106 is an orally active and selective RET kinase inhibitor with IC50s of 0.4 nM, 0.2 nM for human RET and rat RET, respectively. GSK3179106 has the potential for irritable bowel syndrome (IBS) through the attenuation of post-inflammatory and stress-induced visceral hypersensitivity[1].
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[1].
| 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[1] |
| 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. |
References
[1] Russell JP, et al. Exploring the Potential of RET Kinase Inhibition for Irritable Bowel Syndrome: A Preclinical Investigation in Rodent Models of Colonic Hypersensitivity. J Pharmacol Exp Ther. 2019 Feb;368(2):299-307. DOI:10.1124/jpet.118.252973
[2] Russell JP, et al. Enteric RET inhibition attenuates gastrointestinal secretion and motility via cholinergic signaling in rat colonic mucosal preparations. Neurogastroenterol Motil. 2019 Apr;31(4):e13479. DOI:10.1111/nmo.13479
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