Zamaporvint (RXC004) is an orally active and selective inhibitor of Wnt. Zamaporvint targete membrane-bound o-acyltransferase Porcupine and inhibited Wnt ligand palmitoylation, secretion, and pathway activation. Zamaporvint displays a favorable pharmacokinetic profile and shows potent antiproliferative effects in Wnt ligand-dependent colorectal and pancreatic cell lines. Zamaporvint possesses multiple antitumor mechanisms and can be used in cancer research[1].
LGK974 is a potent and specific Porcupine (PORCN) inhibitor with an IC50 of 0.1 nM.
Wnt-C59 (C59) is a highly potent and oral porcupine (PORCN) inhibitor with an IC50 of 74 pM.
IWP-O1 is a highly potent Porcupine (Porcn) inhibitor, with an EC50 of 80 pM in L-Wnt-STF cells, suppressing the phosphorylation of Dvl2/3 and LRP6 in HeLa cells. IWP-O1 functions by preventing the secretion of Wnt proteins[1].
GNF-6231 is a potent, selective, and orally bioavailable Porcupine inhibitor that blocks Wnt signaling.1) GNF-6231 shows IC50s of greater than 10 μM on all CYP isoforms tested2) GNF-6231 have favorable potency and a PK profile across preclinical species upon oral administration.3) The reference for orally in MMTV-Wnt1 tumor bearing mice is dosed at 3 mg/kg.4) GNF-6231 showed very robust dose-related antitumor efficacy.
IWP L6 is a Porcn inhibitor with EC50 of 0.5 nM.IC50 Value: 0.5 nM(EC50) [1]Target: Porcupinein vitro: IWP-L6 effectively suppressed the phosphorylation of dishevelled 2 (Dvl2) in HEK293 cells, a biochemical event associated with many Wnt-dependent cellular responses. IWP-L6 inhibits Wnt mediated branching morphogenesis in cultured embryonic kidneys [1].in vivo: IWP-L6 is stable in human plasma over 24 h, it was rapidly metabolized in rat plasma (t1/2 = 190 min), murine plasma (t1/2 = 2 min), and the murine liver S9 fractions (t1/2 = 26 min). The major metabolites are the amide cleavage products. Similar species-dependent metabolitic profiles due to the involvement of carboxylesterase (CES) have been reported with other drug candidates. Despite its modest metabolic stability in mouse-derived plasma, IWP-L6 was highly active in zebrafish. IWP-L6 exhibited more potent activity [1].
Porcupine-IN-1 is potent porcupine inhibitor with an IC50 of 0.5±0.2 nM.