5.00496

Porcn Inhibitor II, C59

• Synonym(s): Porcn Inhibitor II, C59, Wnt-C59, Wnt Pathway Inhibitor XVI, 2-(4-(2-Methylpyridin-4-yl)phenyl)-N-(4-(pyridin-3-yl)phenyl)acetamide
• Empirical Formula (Hill Notation): C₂₅H₂₁N₃O
• CAS Number: 1243243-89-1
• Molecular Weight: 379.45
• UNSPSC Code: 12352200

Properties

• Assay: ≥99% (HPLC)
• Quality Level: 100
• form: powder
• manufacturer/tradename: Calbiochem^®
• storage condition: OK to freeze; protect from light
• color: off-white
• solubility: DMSO: 100 mg/mL
• storage temp.: 2-8°C
• InChI: 1S/C25H21N3O/c1-18-15-22(12-14-27-18)20-6-4-19(5-7-20)16-25(29)28-24-10-8-21(9-11-24)23-3-2-13-26-17-23/h2-15,17H,16H2,1H3,(H,28,29)
• InChI key: KHZOJCQBHJUJFY-UHFFFAOYSA-N

Description

General description

A cell-permeable pyridinylphenyl-acetamide that is much more potent than IWP-2 (Cat. No. 681671) in inhibiting MBOAT (membrane-bound O-acyltranferase) family member Porcn- (Porcupine) mediated Wnt palmitoylation (IC₅₀ = 74 pM in STF reporter assays using Wnt3a-transfected HEK293 cells). Shown to be effective against Porcn of murine (mPorcn-A, B, C, D) and human (hPorcn-B), but not xenopus (xPorcn-A), species and potently inhibit the processing of both canonical (1, 2, 3a, 6, 7b, 8a, 9a, 9b, 10) and non-canonical (4, 5a, 11, 16) Wnt subtypes. C59 is orally active in mice (t_1/2 = 1.94 h; plasma [C59]_{t = 24 h} = 3 nM; 5 mg/mL p.o.) and demonstrated to effectively suppress MMTV-WNT1 tumor expansion in both immunodeficient female nude mice (Ave fold of tumor expansion = 3 vs.19 in 17 days with or without daily 10 mg/kg oral dosage) and in immunocompetent female nulliparous mice (Ave fold of tumor expansion = 0.8 vs.3.7 in 21 days with or without daily 5 mg/kg oral dosage) in vivo.

A cell-permeable pyridinylphenyl-acetamide that is much more potent than IWP-2 (Cat. No. 681671) in inhibiting MBOAT family member Porcupine-mediated Wnt palmitoylation (IC₅₀ = 74 pM in STF reporter assays using Wnt3a-transfected HEK293). Shown to be effective against Porcn of murine and human, but not xenopus, species and potently inhibit the processing of both canonical and non-canonical Wnt subtypes. C59 is demonstrated to be orally active and effectively suppress MMTV-WNT1 tumor expansion in mice (5 mg/kg & 10 mg/kg p.o.) in vivo.

Please note that the molecular weight for this compound is batch-specific due to variable water content. Please refer to the vial label or the certificate of analysis for the batch-specific molecular weight. The molecular weight provided represents the baseline molecular weight without water.

Biochem/physiol Actions

Cell permeable: yes

Primary Target
Porcupine (Porcn)-mediated Wnt palmitoylation

Reversible: yes

Packaging

Packaged under inert gas

Warning

Toxicity: Standard Handling (A)

Reconstitution

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.

Other Notes

Proffitt, K.D., et al. 2013. Cancer Res.73, 502.

Legal Information

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Safety Information

• Storage Class Code: 11 - Combustible Solids
• WGK: WGK 2
• Flash Point(F): Not applicable
• Flash Point(C): Not applicable