Synonym
GNF6231; GNF-6231; GNF 6231
IUPAC/Chemical Name
N-[5-(4-Acetylpiperazin-1-yl)pyridin-2-yl]-2-[6-(2-fluoropyridin-4-yl)-5-methylpyridin-3-yl]acetamide
InChi Key
AXXNRMISICMFNS-UHFFFAOYSA-N
InChi Code
InChI=1S/C24H25FN6O2/c1-16-11-18(14-28-24(16)19-5-6-26-21(25)13-19)12-23(33)29-22-4-3-20(15-27-22)31-9-7-30(8-10-31)17(2)32/h3-6,11,13-15H,7-10,12H2,1-2H3,(H,27,29,33)
SMILES Code
O=C(NC1=NC=C(N2CCN(C(C)=O)CC2)C=C1)CC3=CC(C)=C(C4=CC(F)=NC=C4)N=C3
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
>3 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
Biological target:
GNF-6231 is a potent, selective, and orally bioavailable Porcupine inhibitor that blocks Wnt signaling.
In vitro activity:
Compound 19 (GNF-6231) exhibits exquisite specificity for PORCN. In this study’s broad off-target panel profiling, there are no appreciable activities observed, at least up to 10 μM testing concentrations, for more than 200 off-targets, which include GPCRs, kinases, proteases, transporters, ion channels, and nuclear receptors. Like the other analogues, compound 19 shows IC50s of greater than 10 μM on all CYP isoforms tested (2C9, 2D6, 3A4).
Reference: ACS Med Chem Lett. 2016 May 10;7(7):676-80. https://pubmed.ncbi.nlm.nih.gov/27437076/
In vivo activity:
The percent infarct area, as determined by blinded histomorphometry of Masson’s trichrome stained left-ventricular sections (Figures 3E and and3F)3F) by a pathologist at day 30, was significantly lower in GNF-6231 treated hearts compared to vehicle control (9.07 ± 3.99% in GNF-6231 treated vs. 17.18 ± 4.97% in vehicle-treated; p=0.0152), indicative of a reduction in myocardial scarring with WNT inhibition. Hence, GNF-6231 augmented overall cardiac repair and recovery following LV infarct.
Reference: Cell Stem Cells Regen Med. 2016 Nov;2(2):10.16966/2472-6990.111. https://pubmed.ncbi.nlm.nih.gov/28042617/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
62.5 |
139.35 |
| Ethanol |
5.0 |
11.15 |
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
448.50
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.
| 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. Cheng D, Liu J, Han D, Zhang G, Gao W, Hsieh MH, Ng N, Kasibhatla S, Tompkins C, Li J, Steffy A, Sun F, Li C, Seidel HM, Harris JL, Pan S. Discovery of Pyridinyl Acetamide Derivatives as Potent, Selective, and Orally Bioavailable Porcupine Inhibitors. ACS Med Chem Lett. 2016 May 10;7(7):676-80. doi: 10.1021/acsmedchemlett.6b00038. PMID: 27437076; PMCID: PMC4948009.
2. Bastakoty D, Saraswati S, Joshi P, Atkinson J, Feoktistov I, Liu J, Harris JL, Young PP. Temporary, Systemic Inhibition of the WNT/β-Catenin Pathway promotes Regenerative Cardiac Repair following Myocardial Infarct. Cell Stem Cells Regen Med. 2016 Nov;2(2):10.16966/2472-6990.111. doi: 10.16966/2472-6990.111. Epub 2016 May 30. PMID: 28042617; PMCID: PMC5193163.
In vitro protocol:
1. Cheng D, Liu J, Han D, Zhang G, Gao W, Hsieh MH, Ng N, Kasibhatla S, Tompkins C, Li J, Steffy A, Sun F, Li C, Seidel HM, Harris JL, Pan S. Discovery of Pyridinyl Acetamide Derivatives as Potent, Selective, and Orally Bioavailable Porcupine Inhibitors. ACS Med Chem Lett. 2016 May 10;7(7):676-80. doi: 10.1021/acsmedchemlett.6b00038. PMID: 27437076; PMCID: PMC4948009.
In vivo protocol:
1. Cheng D, Liu J, Han D, Zhang G, Gao W, Hsieh MH, Ng N, Kasibhatla S, Tompkins C, Li J, Steffy A, Sun F, Li C, Seidel HM, Harris JL, Pan S. Discovery of Pyridinyl Acetamide Derivatives as Potent, Selective, and Orally Bioavailable Porcupine Inhibitors. ACS Med Chem Lett. 2016 May 10;7(7):676-80. doi: 10.1021/acsmedchemlett.6b00038. PMID: 27437076; PMCID: PMC4948009.
2. Bastakoty D, Saraswati S, Joshi P, Atkinson J, Feoktistov I, Liu J, Harris JL, Young PP. Temporary, Systemic Inhibition of the WNT/β-Catenin Pathway promotes Regenerative Cardiac Repair following Myocardial Infarct. Cell Stem Cells Regen Med. 2016 Nov;2(2):10.16966/2472-6990.111. doi: 10.16966/2472-6990.111. Epub 2016 May 30. PMID: 28042617; PMCID: PMC5193163.
1: Katoh M. Multi‑layered prevention and treatment of chronic inflammation, organ fibrosis and cancer associated with canonical WNT/β‑catenin signaling activation (Review). Int J Mol Med. 2018 Aug;42(2):713-725. doi: 10.3892/ijmm.2018.3689. Epub 2018 May 17. PMID: 29786110; PMCID: PMC6034925.
2: Chen CW, Beyer C, Liu J, Maier C, Li C, Trinh-Minh T, Xu X, Cole SH, Hsieh MH, Ng N, Althage A, Meeusen S, Pan S, Svensson EC, Seidel HM, Schett G, Gergely P, Harris JL, Distler JH. Pharmacological inhibition of porcupine induces regression of experimental skin fibrosis by targeting Wnt signalling. Ann Rheum Dis. 2017 Apr;76(4):773-778. doi: 10.1136/annrheumdis-2016-210294. Epub 2017 Feb 2. PMID: 28153829.
3: Cheng D, Liu J, Han D, Zhang G, Gao W, Hsieh MH, Ng N, Kasibhatla S, Tompkins C, Li J, Steffy A, Sun F, Li C, Seidel HM, Harris JL, Pan S. Discovery of Pyridinyl Acetamide Derivatives as Potent, Selective, and Orally Bioavailable Porcupine Inhibitors. ACS Med Chem Lett. 2016 May 10;7(7):676-80. doi: 10.1021/acsmedchemlett.6b00038. PMID: 27437076; PMCID: PMC4948009.
4: Bastakoty D, Saraswati S, Joshi P, Atkinson J, Feoktistov I, Liu J, Harris JL, Young PP. Temporary, Systemic Inhibition of the WNT/β-Catenin Pathway promotes Regenerative Cardiac Repair following Myocardial Infarct. Cell Stem Cells Regen Med. 2016 Nov;2(2):10.16966/2472-6990.111. doi: 10.16966/2472-6990.111. Epub 2016 May 30. PMID: 28042617; PMCID: PMC5193163.
