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| 5mg |
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| 25mg |
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| 100mg |
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Purity: ≥98%
GSK3179106 is a novel, potent, selective, and gut-restricted RET kinase inhibitor with an IC50 of 0.4 nM. GSK3179106-induced RET inhibition reduced the amount of CRD-induced abdominal contractions in all of the rat models. According to our research, RET is involved in visceral nociception. A novel therapeutic approach for the treatment of IBS may involve the potent, selective, and gut-restricted small molecule inhibition of RET kinase, which attenuates visceral hypersensitivity induced by stress and post-inflammatory conditions.
| Targets |
RET human (IC50 = 0.4 nM); RET rat (IC50 = 0.2 nM)
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|---|---|
| ln Vitro |
GSK3179106 has good kinase selectivity and a clean genotoxic profile with no embedded genotoxicity liabilities; only 26 of a set of over 300 recombinant kinases are found to be inhibited at a 1 μM test concentration[1].
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| ln Vivo |
GSK3179106, formulated as 0.04 mg/mL in DMSO/6% HP-beta-CD = 5:95 with a pH of 7, displayed low exposure with an AUC of 102 ng·h/mL in male Sprague-Dawley rats after a single IV (bolus, 0.06 mg/kg) PK. Seven doses of 10 mg/kg administered over 3.5 days are used to assess oral PK, following the same dosage schedule as the in vivo colonic hypersensitivity model. In order to better understand the PK/PD relationship, whole gut PK measurements are also performed. These yield high concentrations of GSK3179106 in the colon's contents, as well as in the jejunum, duodenum, and ileum, compared to plasma[1].
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| Animal Protocol |
male Sprague-Dawley rats
0.06 mg/kg IV |
| References |
| Molecular Formula |
C22H21F4N3O4
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|---|---|
| Molecular Weight |
467.413459539413
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| Exact Mass |
467.15
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| Elemental Analysis |
C, 56.53; H, 4.53; F, 16.26; N, 8.99; O, 13.69
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| CAS # |
1627856-64-7
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| Related CAS # |
1627856-64-7;1884420-19-2 (hydrate);
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| PubChem CID |
78427026
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| Appearance |
White to off-white solid powder
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| LogP |
3.4
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
33
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| Complexity |
812
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
IDXKJSSOUXWLDB-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H21F4N3O4/c1-4-32-16-9-19(30)27-11-14(16)12-5-6-13(15(23)7-12)8-20(31)28-18-10-17(33-29-18)21(2,3)22(24,25)26/h5-7,9-11H,4,8H2,1-3H3,(H,27,30)(H,28,29,31)
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| Chemical Name |
2-[4-(4-ethoxy-6-oxo-1H-pyridin-3-yl)-2-fluorophenyl]-N-[5-(1,1,1-trifluoro-2-methylpropan-2-yl)-1,2-oxazol-3-yl]acetamide
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| Synonyms |
GSK-3179106; GSK 3179106; GSK3179106
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: ~93 mg/mL (~199.0 mM)
Ethanol: ~6 mg/mL (~12.8 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.35 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.35 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (5.35 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1394 mL | 10.6972 mL | 21.3945 mL | |
| 5 mM | 0.4279 mL | 2.1394 mL | 4.2789 mL | |
| 10 mM | 0.2139 mL | 1.0697 mL | 2.1394 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT02798991 | Completed | Drug: GSK3179106 Drug: Matched Placebo |
Irritable Bowel Syndrome | GlaxoSmithKline | June 2016 | Phase 1 |
| NCT02727283 | Completed | Drug: GSK3179106 Drug: Placebo |
Irritable Bowel Syndrome | GlaxoSmithKline | November 26, 2015 | Phase 1 |
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