raw material KY19382

KY19382 More Info

Overview

KY19382 is a potent, low-molecular-weight and orally bioavailable dual inhibitor that targets the CXXC5–DVL protein-protein interaction and glycogen synthase kinase-3β (GSK3β) with IC₅₀ values of 19 nM and 10 nM, respectively[^1][^4][^10]. By concomitantly blocking these two negative regulators, KY19382 robustly activates canonical Wnt/β-catenin signalling and has demonstrated efficacy in pre-clinical models of metabolic disease, cartilage repair, and hair regeneration.

Key features

• Mechanism of action: simultaneous disruption of CXXC5–DVL binding and inhibition of GSK3β kinase activity, leading to β-catenin stabilisation and nuclear translocation.

• Route of administration: active after oral gavage or intraperitoneal injection in rodents.

• Selectivity: >100-fold selectivity versus a panel of 50 kinases (in-house safety panel, MCE).

In vitro data

• Promotes proliferation of ATDC5 chondrocyte progenitor cells (BrdU incorporation EC₅₀ ≈ 30 nM)[^1].

• Up-regulates chondrogenic differentiation markers (COL2A1, SOX9) in both ATDC5 and C28/I2 cells at 0.1 μM (48 h).

• Enhances TOPFlash reporter activity in HEK293 cells with an EC₅₀ of 11 nM[^1][^5].

In vivo data

• Growth-plate maturation: 0.1 mg kg⁻¹ i.p. once daily for 2 weeks accelerates tibial growth in fast-growing young mice and delays senescence of the growth plate in aged mice[^1].

• Hair regeneration: topical or systemic application induces anagen in C57BL/6 mice, increases hair-shaft length ex vivo (human follicles and murine vibrissae), and promotes wound-induced hair follicle neogenesis (WIHN)[^5].

• Metabolic syndrome: ameliorates high-fat-diet-induced obesity and insulin resistance in C57BL/6 mice (3 mg kg⁻¹ p.o. b.i.d. for 8 weeks, unpublished).

Chemical & physical properties

• IUPAC name: 5,6-dichloro-3-[3-(methoxyimino)-1,3-dihydro-2H-indol-2-ylidene]-1,3-dihydro-2H-indol-2-one

• Molecular formula: C₁₇H₁₁Cl₂N₃O₂

• Molecular weight: 360.19 g mol⁻¹

• Appearance: orange-red crystalline powder

• Purity (HPLC): ≥98 %

• Solubility: 20 mM in DMSO; 2.4 mg mL⁻¹ in 5 % DMSO + 30 % PEG-400 + 65 % PBS for in vivo dosing.

Storage & handling

• Long term: store at –20 °C as powder, protected from light and moisture.

• Stock solutions: 2 mM in DMSO stable for 6 months at –80 °C; avoid repeated freeze–thaw cycles.

Research applications

• Regenerative medicine: cartilage repair, bone lengthening, hair follicle neogenesis.

• Metabolic disease models: non-alcoholic fatty liver disease (NAFLD), type 2 diabetes.

• Wnt signalling research: probe for β-catenin-dependent transcription studies.

Safety note

For laboratory research only. Not for human or veterinary diagnostic or therapeutic use.