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Formula | C23H20N6O |
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Molecular Weight | 396.44 | CAS No. | 1243244-14-5 | |
Solubility (25°C)* | In vitro | DMSO | 79 mg/mL (199.27 mM) | |
Water | Insoluble | |||
Ethanol | Insoluble | |||
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. * Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.) |
Description | LGK-974 (NVP-LGK974, WNT974) is a potent and specific PORCN inhibitor, and inhibits Wnt signaling with IC50 of 0.4 nM in TM3 cells. Phase 1. | |
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In vitro | LGK974 effectively displaces [3H]-GNF-1331 with IC50 of 1 nM in the PORCN radioligand binding assay, and shows no major cytotoxicity in cells up to 20 µM. LGK974 shows comparable inhibitory activities against all tested Wnts with IC50 ranging from 0.05 to 2.4 nM, which is consistent with the genetic loss of PORCN phenotype. [1] LGK974 specifically inhibits the growth of three RNF43-mutant cell lines, HPAF-II, PaTu 8988S, and Capan-2. [2] | |
In vivo | In a murine MMTV-Wnt1 tumor model and a human head and neck squamous cell carcinoma model (HN30), LGK974 (3 mg/kg) inhibits Wnt signaling in vivo and induces tumor regression without significant body weight loss in the mice. [1] LGK974 (5 mg/kg, p.o., BID) also inhibits tumor growth of RNF43-mutant pancreatic tumors (HPAF-II and Capan-2) in vivo. [2] | |
Features | Orally bioavailable Porcupine-specific inhibitor that has been tested in Phase I clinical trials for treatment of malignancies dependent on Wnt ligands. |
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Data from [Data independently produced by Breast Cancer Res, 2014, 16(4), 408]
Data from [Data independently produced by , , Nat Commun, 2017, 8:15945]
Data from [Data independently produced by , , J Clin Endocrinol Metab, 2015, 100(6): E836-44]
Data from [Data independently produced by , , J Endocrinol, 2018, 238(1):13-23]
Developmental signals control chromosome segregation fidelity during pluripotency and neurogenesis by modulating replicative stress [ Nat Commun, 2024, 15(1):7404] | PubMed: 39191776 |
Loss of ARID3A perturbs intestinal epithelial proliferation-differentiation ratio and regeneration [ J Exp Med, 2024, 221(10)e20232279] | PubMed: 39150450 |
Physiological regulation of neuronal Wnt activity is essential for TDP-43 localization and function [ EMBO J, 2024, 43(16):3388-3413] | PubMed: 38918634 |
GPA33 expression in colorectal cancer can be induced by WNT inhibition and targeted by cellular therapy [ Oncogene, 2024, ] | PubMed: 39472498 |
Unbalancing cAMP and Ras/MAPK pathways as a therapeutic strategy for cutaneous neurofibromas [ JCI Insight, 2024, 9(3)e168826] | PubMed: 38175707 |
Higher overall survival rates of oral squamous cell carcinoma treated with metronomic neoadjuvant chemotherapy [ Am J Cancer Res, 2024, 14(3):1033-1051] | PubMed: 38590400 |
Integrated clinical and genomic analysis identifies driver events and molecular evolution of colitis-associated cancers [ Nat Commun, 2023, 14(1):110] | PubMed: 36611031 |
Sema3C signaling is an alternative activator of the canonical WNT pathway in glioblastoma [ Nat Commun, 2023, 14(1):2262] | PubMed: 37080989 |
WNT signaling in the tumor microenvironment promotes immunosuppression in murine pancreatic cancer [ J Exp Med, 2023, 220(1)e20220503] | PubMed: 36239683 |
The CUT&RUN suspect list of problematic regions of the genome [ Genome Biol, 2023, 24(1):185] | PubMed: 37563719 |
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