GNF-1331 | CAS#603101-22-0 | Porcupine Inhibitor

MedKoo Cat#: 407337 | Name: GNF-1331

Description:

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

GNF-1331 is a Potent, Selective, and Orally Bioavailable Porcupine Inhibitor (IC50 = 12 nM). Blockade of aberrant Wnt signaling is an attractive therapeutic approach in multiple cancers. Wnt signaling is tightly controlled during cellular proliferation, differentiation, and embryonic morphogenesis. Aberrant activation of this pathway plays a critical role in a variety of cancers, such as cutaneous squamous cell carcinoma (SCC), breast cancer, and colorectal cancer.

Chemical Structure

GNF-1331

CAS#603101-22-0

Theoretical Analysis

MedKoo Cat#: 407337

Name: GNF-1331

CAS#: 603101-22-0

Chemical Formula: C20H20N6O2S2

Exact Mass: 440.1089

Molecular Weight: 440.54

Elemental Analysis: C, 54.53; H, 4.58; N, 19.08; O, 7.26; S, 14.55

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Synonym

GNF-1331; GNF 1331; GNF1331

IUPAC/Chemical Name

N-(6-methoxybenzo[d]thiazol-2-yl)-2-((4-propyl-5-(pyridin-4-yl)-4H-1,2,4-triazol-3-yl)thio)acetamide

InChi Key

JIUFLMSAFMXEEC-UHFFFAOYSA-N

InChi Code

InChI=1S/C20H20N6O2S2/c1-3-10-26-18(13-6-8-21-9-7-13)24-25-20(26)29-12-17(27)23-19-22-15-5-4-14(28-2)11-16(15)30-19/h4-9,11H,3,10,12H2,1-2H3,(H,22,23,27)

SMILES Code

O=C(NC1=NC2=CC=C(OC)C=C2S1)CSC3=NN=C(C4=CC=NC=C4)N3CCC

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, not in water

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

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#S8G10M13

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

GNF-1331 is a Potent, Selective, and Orally Bioavailable Porcupine Inhibitor (IC50 = 12 nM).

In vitro activity:

As shown in Fig. 1A, [3H]-GNF-1331 bound well to the membrane preparations from 293 cells transfected with PORCN but not to the membrane preparations from cells transfected with Wntless or a vector control, suggesting that GNF-1331 specifically interacted with PORCN. Furthermore, the specific interaction between GNF-1331 and PORCN could be competed off by unlabeled GNF-1331 (Fig. 1A). Reference: Proc Natl Acad Sci U S A. 2013 Dec 10;110(50):20224-9. https://pubmed.ncbi.nlm.nih.gov/24277854/

In vivo activity:

GNF-1331 shows good potency in the Wnt secretion coculture assay with an IC50 of 12 nM. It binds to PORCN in a radioligand binding assay with an IC50 of 8 nM. However, it exhibits poor pharmacokinetic properties with rapid clearance and low systemic exposure after oral administration in mice (dose normalized Cmax and AUC are 0.03 μM·h and 0.014 μM, respectively), which prevent it from being used in vivo. Reference: ACS Med Chem Lett. 2016 May 10;7(7):676-80. https://pubmed.ncbi.nlm.nih.gov/27437076/

Preparing Stock Solutions

The following data is based on the product molecular weight 440.54 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. Liu J, Pan S, Hsieh MH, Ng N, Sun F, Wang T, Kasibhatla S, Schuller AG, Li AG, Cheng D, Li J, Tompkins C, Pferdekamper A, Steffy A, Cheng J, Kowal C, Phung V, Guo G, Wang Y, Graham MP, Flynn S, Brenner JC, Li C, Villarroel MC, Schultz PG, Wu X, McNamara P, Sellers WR, Petruzzelli L, Boral AL, Seidel HM, McLaughlin ME, Che J, Carey TE, Vanasse G, Harris JL. Targeting Wnt-driven cancer through the inhibition of Porcupine by LGK974. Proc Natl Acad Sci U S A. 2013 Dec 10;110(50):20224-9. doi: 10.1073/pnas.1314239110. Epub 2013 Nov 25. PMID: 24277854; PMCID: PMC3864356.

In vitro protocol:

In vivo protocol:

Discovery of Pyridinyl Acetamide Derivatives as Potent, Selective, and Orally Bioavailable Porcupine Inhibitors Dai Cheng, Jun Liu, Dong Han, Guobao Zhang, Wenqi Gao, Mindy H. Hsieh, Nicholas Ng, Shailaja Kasibhatla, Celin Tompkins, Jie Li, Auzon Steffy, Fangxian Sun, Chun Li, H. Martin Seidel, Jennifer L. Harris, and Shifeng Pan Publication Date (Web): May 10, 2016 (Letter) DOI: 10.1021/acsmedchemlett.6b00038