[CAS NO. 1243244-14-5] LGK974
PRODUCTS SPECIFICATIONS [1243244-14-5]
DESCRIPTION [1243244-14-5]
Overview
| MDL | MFCD27501026 |
|---|---|
| Molecular Weight | 396.44 |
| Molecular Formula | C23H20N6O |
| SMILES | O=C(NC1=NC=C(C2=NC=CN=C2)C=C1)CC3=CN=C(C4=CC(C)=NC=C4)C(C)=C3 |
17 Publications Citing Use of MCE
- [1]Nature. 2017 May 18;545(7654):355-359.
- [2]Cell Stem Cell. 2022 Aug 4;29(8):1246-1261.e6.
- [3]Cell Stem Cell. 2020 Sep 3;27(3):413-429.e4.
- [4]Sci Immunol. 2021 Nov 12;6(65):eabc6424.
- [5]Nat Commun. 2019 Mar 27;10(1):1382.
- [6]Neuro Oncol. 2023 Jan 2;noac288.
- [7]Bioact Mater. 2 January 2022.
- [8]Oncogene. 2019 Mar;38(11):1951-1965.
- [9]Cancer Lett. 2022 Nov 24;216023.
- [10]Neurotherapeutics. 2021 Jan;18(1):601-614.
- [11]Exp Mol Med. 2021 Mar 10.
- [12]J Biol Chem. 2018 Dec 21;293(51):19710-19724.
- [13]Exp Cell Res. 2016 Jul 15;345(2):206-17.
- [14]Drug Des Devel Ther. 2020 Aug 12;14:3301-3313.
- [15]Research Square Print. September 2nd, 2022.
- [16]bioRxiv. May 20, 2022.
- [17]Research Square Preprint. 2021 Aug.
Summary
IC50 & Target
Porcupine [1]
In Vitro
LGK974 effectively displaces [ 3 H]-GNF-1331 with an IC 50 of 1 nM in the PORCN radioligand binding assay. LGK974 potently reduces Wnt-dependent AXIN2 mRNA levels in HN30 cells with an IC 50 of 0.3 nM [1] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
LGK974, a drug that targets Porcupine, a Wnt-specific acyltransferase. LGK974 potently inhibits Wnt signaling, has strong efficacy in rodent tumor models, and is well-tolerated. Toxicology studies are performed on nontumor bearing rats at 3 and 20 mg/kg. At the efficacious dose of 3 mg/kg per day for 14 d, LGK974 is well-tolerated without abnormal histopathological findings in Wnt-dependent tissues, including the intestine, stomach, and skin. When rats are administrated a very high dose of 20 mg/kg per day for 14 d, loss of intestinal epithelium is observed, consistent with the concept that Wnt is required for intestinal tissue homeostasis [1] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Clinical Trial
| NCT Number | Sponsor | Condition | Start Date | Phase |
|---|---|---|---|---|
| NCT02278133 | Array BioPharma |
Metastatic Colorectal Cancer
|
December 2014 | Phase 1|Phase 2 |
| NCT02649530 | University of Michigan Rogel Cancer Center |
Squamous Cell Carcinoma, Head And Neck
|
Phase 2 | |
| NCT01351103 | Novartis Pharmaceuticals|Novartis |
Pancreatic Cancer|BRAF Mutant Colorectal Cancer|Melanoma|Triple Negative Breast Cancer|Head and Neck Squamous Cell Cancer|Cervical Squamous Cell Cancer|Esophageal Squamous Cell Cancer|Lung Squamous Cell Cancer
|
December 1, 2011 | Phase 1 |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
| Powder | -20°C | 3 years |
|---|---|---|
| 4°C | 2 years | |
| In solvent | -80°C | 6 months |
| -20°C | 1 month |
Solvent & Solubility
DMSO : ≥ 32 mg/mL ( 80.72 mM )
* "≥" means soluble, but saturation unknown.
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 2.5224 mL | 12.6122 mL | 25.2245 mL |
| 5 mM | 0.5045 mL | 2.5224 mL | 5.0449 mL |
| 10 mM | 0.2522 mL | 1.2612 mL | 2.5224 mL |
References
- [1] Liu J, et al. 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.
- [2] Tammela T, et al. A Wnt-producing niche drives proliferative potential and progression in lung adenocarcinoma. Nature. 2017 May 18;545(7654):355-359.