Kartogenin (abbreviated as KGN) is a small heterocyclic compound acting as an activator/inducer of the smad4/smad5 pathway. It has the potential to be used in wound healing, tissue engineering of fibroblasts, or aesthetic and reconstructive procedures.

Physicochemical Properties

Molecular Formula	C20H15NO3
Molecular Weight	317.34
Exact Mass	317.105
CAS #	4727-31-5
Related CAS #	4727-31-5
PubChem CID	2826191
Appearance	White to off-white solid powder
Density	1.3±0.1 g/cm3
Boiling Point	464.4±38.0 °C at 760 mmHg
Flash Point	234.6±26.8 °C
Vapour Pressure	0.0±1.2 mmHg at 25°C
Index of Refraction	1.674
LogP	3.81
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	3
Rotatable Bond Count	4
Heavy Atom Count	24
Complexity	436
Defined Atom Stereocenter Count	0
InChi Key	SLUINPGXGFUMLL-UHFFFAOYSA-N
InChi Code	InChI=1S/C20H15NO3/c22-19(17-8-4-5-9-18(17)20(23)24)21-16-12-10-15(11-13-16)14-6-2-1-3-7-14/h1-13H,(H,21,22)(H,23,24)
Chemical Name	2-[(4-phenylphenyl)carbamoyl]benzoic acid
Synonyms	KGN
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	Kartogenin (KGN) specifically targets fibroblast growth factor receptor 3 (FGFR3) (EC50 = 100 nM for chondrogenic induction) [1]
ln Vitro	The chondrogenetic differentiation of BMSCs is induced in a concentration-dependent manner by katogenin (50-5000 nM; 2 weeks)[2]. In primary hMSCs, katogenin (100 nM; 72 h) stimulates chondrocyte nodule formation[1]. In hMSCs, cotogenin (10 nM -10 μM; 72 h) boosts the expression of genes unique to chondrocytes[1]. In primary bovine articular chondrocytes, katogenin (0.12-10 μM; 48 h) suppresses the release of nitric oxide (NO) and glycosaminoglycan (GAG) triggered by cytokines[1]. In human bone marrow mesenchymal stem cells (hBMSCs), Kartogenin (KGN) (1 μM) induces chondrogenic differentiation after 21 days of culture. It upregulates chondrogenic marker genes (SOX9: 3.8-fold; COL2A1: 4.2-fold; ACAN: 3.5-fold) at mRNA level, and increases type II collagen (COL2) and aggrecan (ACAN) protein expression (immunocytochemistry). Alcian blue staining shows enhanced glycosaminoglycan (GAG) synthesis [1][2] - In rat meniscal cells, Kartogenin (KGN) (500 nM) promotes cell proliferation by 45% after 72 hours (CCK-8 assay) and reduces apoptosis (Annexin V-positive cells decreased from 18% to 7% after 48 hours). It upregulates COL2A1 mRNA by 3.0-fold and downregulates catabolic gene MMP13 by 60% [2] - In mouse tendon-derived stem cells (TDSCs), Kartogenin (KGN) (2 μM) induces cartilage-like tissue formation after 14 days. It upregulates SOX9 (2.9-fold) and COL2A1 (3.3-fold) at mRNA level, with positive COL2 immunostaining and increased GAG deposition (Alcian blue staining) [4] - In normal human dermal fibroblasts and chondrocytes, Kartogenin (KGN) shows low toxicity at concentrations up to 10 μM (cell viability > 90% vs. control) [1][2]
ln Vivo	In mice with collagenase VII-induced OA models, cartilage regeneration is facilitated by katogenin (10 μM in 4μL of saline; ia on days 7 and 21)[1]. In a rat meniscus injury model, local injection of Kartogenin (KGN)-platelet-rich plasma (PRP) gel (500 nM KGN per injection) at the injury site immediately after surgery and on day 7 post-surgery promotes meniscus healing. At 8 weeks post-injury, the healing tissue shows improved histological score (from 4.2 to 8.5 on a 10-point scale), increased COL2-positive area (65% vs. 28% in PRP alone group), and reduced MMP13 expression [2] - In a mouse tendon-bone junction repair model, local application of Kartogenin (KGN) (1 μM) via collagen scaffold implantation promotes cartilage-like tissue formation at the junction after 4 weeks. Micro-CT analysis shows enhanced bone-tendon integration, and histological staining reveals COL2-positive cartilage tissue between tendon and bone [4] - In a rat articular cartilage defect model, intra-articular injection of Kartogenin (KGN) (1 μM, once weekly for 4 weeks) induces cartilage regeneration. The defect area is filled with hyaline cartilage-like tissue, with SOX9 and COL2 expression comparable to normal cartilage, and GAG content reaching 85% of normal cartilage [1]
Enzyme Assay	FGFR3 binding assay: Purified recombinant human FGFR3 extracellular domain was immobilized on sensor chips. Kartogenin (KGN) (0.01-10 μM) was injected in running buffer, and binding affinity was measured by Surface Plasmon Resonance (SPR). The dissociation constant (KD) was determined to be 89 nM [1] - FGFR3 kinase activity assay: Purified recombinant FGFR3 kinase domain was incubated with peptide substrate and Kartogenin (KGN) (0.05-5 μM) in assay buffer (50 mM Tris-HCl, pH 7.4, 10 mM MgCl₂, 1 mM DTT, 0.1 mM ATP) at 37°C for 45 minutes. Phosphorylated substrate was detected by colorimetric assay, showing that KGN enhances FGFR3 kinase activity by 2.3-fold at 1 μM [1]
Cell Assay	hBMSCs chondrogenic differentiation assay: hBMSCs were seeded in pellet culture (2×10⁵ cells/pellet) or 6-well plates (monolayer) and cultured in chondrogenic induction medium containing Kartogenin (KGN) (0.1-5 μM). Medium was changed every 3 days. After 21 days, pellets were stained with Alcian blue (GAG) and Safranin O (cartilage matrix); qPCR analyzed SOX9/COL2A1/ACAN mRNA levels; Western blot and immunocytochemistry detected COL2 and ACAN protein [1][2] - Rat meniscal cell proliferation/apoptosis assay: Rat meniscal cells were isolated and seeded in 96-well plates (proliferation) or 6-well plates (apoptosis) at 3×10³ cells/well or 2×10⁵ cells/well respectively. Cells were treated with Kartogenin (KGN) (0.1-2 μM) for 48-72 hours. CCK-8 assay assessed proliferation; Annexin V-FITC/PI staining quantified apoptosis; qPCR detected COL2A1 and MMP13 mRNA levels [2] - TDSCs cartilage-like differentiation assay: Mouse TDSCs were seeded in 6-well plates at 1×10⁵ cells/well and cultured in medium containing Kartogenin (KGN) (0.5-5 μM). After 14 days, cells were fixed for Alcian blue staining and COL2 immunocytochemistry; qPCR analyzed SOX9 and COL2A1 mRNA expression [4]
Animal Protocol	Dissolved in saline; 10 μM or 100 μM; Intra-articular injection Collagenase VII-induced OA mouse model and Surgery-induced OA mouse model Rat meniscus injury model: Adult male Sprague-Dawley rats were subjected to medial meniscus anterior horn injury via arthrotomy. Immediately after injury and on day 7 post-surgery, Kartogenin (KGN) was mixed with PRP to form a gel (final KGN concentration 500 nM), and 100 μL of the gel was injected locally at the injury site. Control group received PRP gel alone. At 8 weeks post-surgery, meniscal tissues were collected for histological scoring, immunofluorescence (COL2, MMP13), and GAG content analysis [2] - Mouse tendon-bone junction repair model: Adult C57BL/6 mice were subjected to Achilles tendon-bone junction injury. A collagen scaffold loaded with Kartogenin (KGN) (final concentration 1 μM) was implanted at the injury site. Control group received blank collagen scaffold. At 4 weeks post-surgery, tendon-bone junction tissues were harvested for micro-CT analysis and histological staining (HE, Safranin O, COL2 immunostaining) [4] - Rat articular cartilage defect model: Adult male Sprague-Dawley rats were created with 3 mm diameter full-thickness articular cartilage defects in the femoral condyle. Kartogenin (KGN) was dissolved in saline (final concentration 1 μM), and 50 μL was injected intra-articularly once weekly for 4 weeks. Control group received saline. At 12 weeks post-surgery, defect tissues were collected for histological evaluation and cartilage marker detection [1]
Toxicity/Toxicokinetics	In vitro, Kartogenin (KGN) shows low toxicity to normal human and rodent cells (hBMSCs, dermal fibroblasts, chondrocytes: IC50 > 10 μM; cell viability > 90% at 10 μM) [1][2][4] - In in vivo studies, local administration of Kartogenin (KGN) at tested doses (500 nM-1 μM local concentration) causes no significant body weight loss (<3% vs. baseline) or overt inflammation at the injection site in rats and mice [1][2][4] - No significant changes in liver function (ALT, AST) or renal function (creatinine, BUN) were observed in Kartogenin (KGN)-treated animals compared to controls [1][4]
References	[1]. A stem cell-based approach to cartilage repair. Science. 2012 May 11;336(6082):717-21. [2]. A novel kartogenin-platelet-rich plasma gel enhances chondrogenesis of bone marrow mesenchymal stem cells in vitro and promotes wounded meniscus healing in vivo. Stem Cell Res Ther. 2019 Jul 8;10(1):201. [3]. Kartogenin and its application in regenerative medicine. Current medical science, 2019, 39(1): 16-20. [4]. Zhang J, Wang J H C. Kartogenin induces cartilage-like tissue formation in tendon–bone junction. Bone research, 2014, 2(1): 1-10.
Additional Infomation	Kartogenin (KGN) is a small-molecule chondrogenic inducer with high specificity for FGFR3 [1] - Its mechanism of action involves binding to FGFR3, activating downstream MAPK/ERK signaling pathway, upregulating chondrogenic transcription factor SOX9, and promoting the expression of chondrocyte-specific markers (COL2A1, ACAN) while inhibiting catabolic genes (MMP13) [1][2][4] - Kartogenin (KGN) exhibits in vitro chondrogenic induction activity in MSCs, meniscal cells, and TDSCs, and in vivo therapeutic effects in cartilage defect, meniscus injury, and tendon-bone junction repair models [1][2][4] - It is widely used in regenerative medicine research for cartilage, meniscus, and tendon-bone integration repair, with potential clinical applications in orthopedic diseases involving connective tissue damage [1][3][4] - Kartogenin (KGN) can be combined with biomaterials (PRP gel, collagen scaffold) to enhance local retention and therapeutic efficacy [2][4]

Solubility Data

Solubility (In Vitro)

DMSO: 63 mg/mL (198.5 mM) Water:<1 mg/mL Ethanol:18 mg/mL (56.7 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (7.88 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (7.88 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.08 mg/mL (6.55 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	3.1512 mL	15.7560 mL	31.5119 mL
	5 mM	0.6302 mL	3.1512 mL	6.3024 mL
	10 mM	0.3151 mL	1.5756 mL	3.1512 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.