KY-19382

KY19382 (also written KY-19382) is 5,6-dichloroindirubin-3′-methoxime, a synthetic small molecule from Kang-Yell Choi's group at Yonsei University, Seoul. From 60 new indirubin derivatives, the group picked KY19382 because it blocked CXXC5, a negative regulator of Wnt signaling, from binding Dishevelled and also inhibited GSK-3β (Choi et al., 2019).

All published work is preclinical, and several papers disclose that the senior author leads a company licensed to develop it (Ryu et al., 2021).

PubChem holds three KY19382 records with this formula and weight (CIDs 148959784, 137473598 and 164575812) that differ only in the drawn geometry of the methoxime double bond. All three carry 2226664-93-1 as a depositor-supplied synonym, with no separate CAS annotation. This page cites CID 148959784, the record with the fullest synonym list.

Published work on KY19382 falls into six areas, all preclinical. Eight of the 11 PubMed records that name it come from the developing laboratory; one wound study and two cancer-cell studies are from independent groups.

How KY19382 activates Wnt/β-catenin signaling

The developers screened for compounds that stop CXXC5, a negative feedback regulator, from binding the PDZ domain of Dishevelled (DVL). In cell-free assays KY19382 blocked that binding with an IC50 of 19 nM and inhibited GSK-3β with an IC50 of 10 nM.

In ATDC5 mouse chondrogenic cells it raised β-catenin and the Wnt targets Axin2 and Wisp1 without significantly changing 19 target genes of other pathways (Choi et al., 2019). In human dermal papilla cells, 5 µM raised β-catenin and alkaline phosphatase, a marker of hair-inducing activity, and β-catenin knockdown abolished that rise (Ryu et al., 2021). Models: cell-free assays, mouse and human cells.

KY19382 in hair follicle models

On shaved backs of 7-week-old male C57BL/6N mice in the resting (telogen) phase, 0.5 mM KY19382 applied daily for 28 days gave more regrown hair by weight, more hair follicles and thicker dermis, signs of growth (anagen) phase entry, than 100 mM minoxidil (n = 5 per group). It also raised wound-induced hair follicle neogenesis, counted as new alkaline phosphatase-positive follicles in 1 cm² wounds on 3-week-old mice (Ryu et al., 2021).

In diabetic mice (high-fat diet plus streptozotocin), 1.5 mM KY19382, but not minoxidil, restored anagen entry after plucking and follicle neogenesis in wounds, and 1 µM restored elongation of human follicles cultured in high glucose. The authors say full follicle regeneration in diabetic wounds still needs confirmation (Ryu et al., 2022). Adding the PKM2 activator TEPP-46 to 0.5 mM KY19382 raised regrowth and neogenesis beyond either alone (Ryu et al., 2022). Models: mice and cultured human follicles.

Skin wound closure models

In HaCaT keratinocytes and adult human dermal fibroblasts, 0.1 and 1 µM KY19382 raised migration, β-catenin, keratin 14, collagen I and α-SMA, and β-catenin knockdown blocked the effect. In male C3H mice with 1 cm full-thickness wounds, 0.05 or 0.1 mM applied daily sped wound closure and re-epithelialization, mostly complete by day 12 at 0.1 mM and ahead of an EGF comparison group (n = 6 per group) (Yoon et al., 2023).

With TEPP-46, 1 mM KY19382 sped closure further; at day 14, wounds given either agent alone still had scabs (Kim et al., 2023). An independent Nanjing group reported smaller wound areas, more collagen and more VEGFA and CD31 staining in streptozotocin-diabetic C57BL/6 mice given KY19382 at splinted wounds. Its cell work used 0.1 mM, at which fibroblast and endothelial cell growth fell by 72 hours (Chen et al., 2025). Models: human skin cells and mice.

Growth plate and bone length in young mice

Male C57BL/6 mice given 0.1 mg/kg KY19382 intraperitoneally each day for 2 weeks, from 3 or 7 weeks of age, had taller growth plates, more proliferating chondrocytes and more nuclear β-catenin. Daily exposure from 3 to 13 weeks of age lengthened the tibia compared with vehicle, with no histological abnormalities reported in articular cartilage or liver and no body weight difference (Choi et al., 2019). Model: male mice.

Cancer cell and skin tumor models

Given the role of Wnt signaling in cancer, the developers tested KY19382 in cutaneous squamous cell carcinoma (cSCC). In HSC-1 and HSC-5 human cSCC cells, 5 µM reduced proliferation, migration, invasion and colony formation, lowered CDK1, and lowered rather than raised Wnt/β-catenin signaling. Applied at 2 mM before each tumor-promoter application for 24 weeks in DMBA/TPA-exposed male C57BL/6 mice, it reduced tumor number and size (n = 10 per group) (Lee et al., 2025).

Independent groups used it as a Wnt agonist tool: 1 µM restored proliferation of lung adenocarcinoma cells after DYNLL1 knockdown (Li et al., 2025), and it reversed the loss of EMT and proliferation after STMN2 silencing in pancreatic cancer cells (Shao et al., 2023). Models: human cancer cells and mice.

Formulation for skin delivery

KY19382 is poorly soluble in water. Premixed 1:1 with hydroxypropyl-β-cyclodextrin, it dissolved at about 5 mg/mL in polyoxyl castor oil and polysorbate 80, and 3.1 mg/mL in PEG 400. A micellar mix of these three raised permeation through an artificial skin membrane compared with DMSO and stayed free of precipitate for 3 months at 4 and 25°C (Seo et al., 2020). Model: in vitro formulation tests.