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MedKoo Cat#: 555258 | Name: GSK3179106
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Description:

WARNING: This product is for research use only, not for human or veterinary use.

GSK3179106 is a potent, selective, and gut-restricted pyridone hinge binder small molecule RET kinase inhibitor with a RET IC50 of 0.3 nM and is efficacious in vivo. GSK3179106 is being developed by GlaxoSmithKline for the treatment of irritable bowel syndrome. GSK3179106 showed IC50s of 0.4 and 11 nM in the biochemical assay and cellular assay, respectively. GSK3179106 had a clean genotoxic profile with no embedded genotoxicity liabilities.

Chemical Structure

GSK3179106
GSK3179106
CAS#1627856-64-7

Theoretical Analysis

MedKoo Cat#: 555258

Name: GSK3179106

CAS#: 1627856-64-7

Chemical Formula: C22H21F4N3O4

Exact Mass: 467.1468

Molecular Weight: 467.42

Elemental Analysis: C, 56.53; H, 4.53; F, 16.26; N, 8.99; O, 13.69

Price and Availability

Size Price Availability Quantity
5mg USD 150.00 Ready to ship
10mg USD 250.00 Ready to ship
25mg USD 450.00 Ready to ship
50mg USD 750.00 Ready to ship
100mg USD 1,250.00 Ready to ship
200mg USD 2,050.00 Ready to ship
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Related CAS #
1627856-64-7 1884420-19-2 (hydrate)
Synonym
GSK3179106; GSK-3179106; GSK 3179106.
IUPAC/Chemical Name
2-(4-(4-ethoxy-6-oxo-1,6-dihydropyridin-3-yl)-2-fluorophenyl)-N-(5-(1,1,1-trifluoro-2-methylpropan-2-yl)isoxazol-3-yl)acetamide
InChi Key
IDXKJSSOUXWLDB-UHFFFAOYSA-N
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)
SMILES Code
O=C(NC1=NOC(C(C)(C)C(F)(F)F)=C1)CC2=CC=C(C(C(OCC)=C3)=CNC3=O)C=C2F
Appearance
Solid powder
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
Inhibition of RET in the ENS represents a novel therapeutic strategy for the normalization of neuronal function and the symptoms of IBS patients.
Biological target:
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.
In vitro activity:
Compound 15 (GSK3179106) was a potent RET inhibitor with IC50s of 0.4 and 11 nM in the biochemical assay and cellular assay, respectively. In addition, it had a clean genotoxic profile with no embedded genotoxicity liabilities. Compound 15 possessed good kinase selectivity; only 26 out of a set of >300 recombinant kinases were found to be inhibited at a 1 μM test concentration (Supporting Information, Table S4). Reference: ACS Med Chem Lett. 2018 May 24;9(7):623-628. https://pubmed.ncbi.nlm.nih.gov/30034590/
In vivo activity:
In comparison with rats that had developed colonic hypersensitivity after exposure to early life stress induced by limited nesting or maternal separation stress and dosed with vehicle, rats orally dosed with GSK3179106 exhibited a decreased VMR (32%–42% inhibition) to colonic distension (Fig. 5, A and B). Reference: J Pharmacol Exp Ther. 2019 Feb;368(2):299-307. https://pubmed.ncbi.nlm.nih.gov/30413627/
Solvent mg/mL mM
Solubility
DMSO 81.0 173.29
DMSO:PBS (pH 7.2) (1:3) 0.3 0.53
Ethanol 15.5 33.16
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 467.42 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol:
1. Russell JP, Mohammadi E, Ligon C, Latorre R, Johnson AC, Hoang B, Krull D, Ho MW, Eidam HS, DeMartino MP, Cheung M, Oliff AI, Kumar S, Greenwood-Van Meerveld B. 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. Epub 2018 Oct 12. PMID: 30311722. 2. Schenck Eidam H, Russell J, Raha K, DeMartino M, Qin D, Guan HA, Zhang Z, Zhen G, Yu H, Wu C, Pan Y, Joberty G, Zinn N, Laquerre S, Robinson S, White A, Giddings A, Mohammadi E, Greenwood-Van Meerveld B, Oliff A, Kumar S, Cheung M. Discovery of a First-in-Class Gut-Restricted RET Kinase Inhibitor as a Clinical Candidate for the Treatment of IBS. ACS Med Chem Lett. 2018 May 24;9(7):623-628. doi: 10.1021/acsmedchemlett.8b00035. PMID: 30034590; PMCID: PMC6047170. 3. Russell JP, Mohammadi E, Ligon CO, Johnson AC, Gershon MD, Rao M, Shen Y, Chan CC, Eidam HS, DeMartino MP, Cheung M, Oliff AI, Kumar S, Greenwood-Van Meerveld B. 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. Epub 2018 Nov 9. PMID: 30413627; PMCID: PMC6346376.
In vitro protocol:
1. Russell JP, Mohammadi E, Ligon C, Latorre R, Johnson AC, Hoang B, Krull D, Ho MW, Eidam HS, DeMartino MP, Cheung M, Oliff AI, Kumar S, Greenwood-Van Meerveld B. 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. Epub 2018 Oct 12. PMID: 30311722. 2. Schenck Eidam H, Russell J, Raha K, DeMartino M, Qin D, Guan HA, Zhang Z, Zhen G, Yu H, Wu C, Pan Y, Joberty G, Zinn N, Laquerre S, Robinson S, White A, Giddings A, Mohammadi E, Greenwood-Van Meerveld B, Oliff A, Kumar S, Cheung M. Discovery of a First-in-Class Gut-Restricted RET Kinase Inhibitor as a Clinical Candidate for the Treatment of IBS. ACS Med Chem Lett. 2018 May 24;9(7):623-628. doi: 10.1021/acsmedchemlett.8b00035. PMID: 30034590; PMCID: PMC6047170.
In vivo protocol:
1. Russell JP, Mohammadi E, Ligon CO, Johnson AC, Gershon MD, Rao M, Shen Y, Chan CC, Eidam HS, DeMartino MP, Cheung M, Oliff AI, Kumar S, Greenwood-Van Meerveld B. 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. Epub 2018 Nov 9. PMID: 30413627; PMCID: PMC6346376. 2. Schenck Eidam H, Russell J, Raha K, DeMartino M, Qin D, Guan HA, Zhang Z, Zhen G, Yu H, Wu C, Pan Y, Joberty G, Zinn N, Laquerre S, Robinson S, White A, Giddings A, Mohammadi E, Greenwood-Van Meerveld B, Oliff A, Kumar S, Cheung M. Discovery of a First-in-Class Gut-Restricted RET Kinase Inhibitor as a Clinical Candidate for the Treatment of IBS. ACS Med Chem Lett. 2018 May 24;9(7):623-628. doi: 10.1021/acsmedchemlett.8b00035. PMID: 30034590; PMCID: PMC6047170.
Discovery of a First-in-Class Gut-Restricted RET Kinase Inhibitor as a Clinical Candidate for the Treatment of IBS Hilary Schenck Eidam, John Russell, Kaushik Raha, Michael DeMartino, Donghui Qin, Huiping Amy Guan, Zhiliu Zhang, Gong Zhen, Haiyu Yu, Chengde Wu, Yan Pan, Gerard Joberty, Nico Zinn, Sylvie Laquerre, Sharon Robinson, Angela White, Amanda Giddings, Ehsan Mohammadi, Beverly Greenwood-Van Meerveld, Allen Oliff, Sanjay Kumar, and Mui Cheung Publication Date (Web): May 24, 2018 (Letter) DOI: 10.1021/acsmedchemlett.8b00035