| Size | Price | Stock | Qty |
|---|---|---|---|
| 10mg |
|
||
| 100mg |
|
||
| 250mg |
|
||
| 500mg | |||
| Other Sizes |
| Targets |
Chromenone 1 targets the bone morphogenetic protein (BMP) signaling pathway, a key regulator of osteogenesis, development, and tissue homeostasis. BMPs are members of the TGFβ superfamily and signal through Smad transcription factors. Chromenone 1 acts as a BMP potentiator by inducing a pronounced, kinase-independent negative TGFβ feedback loop. This feedback enhances nuclear BMP-Smad signaling outputs, promoting osteogenic differentiation and bone formation. The compound's unique mechanism, independent of kinase inhibition, distinguishes it from other BMP modulators. It may also interact with enzymes such as kinases, oxidases, and proteases through its chromenone scaffold. Its ability to modulate BMP/TGFβ signaling makes it a valuable tool for studying bone biology, development, and related diseases.
|
|---|---|
| ln Vitro |
In C2C12 myoblasts, chromanone 1 efficiently induces BMP-dependent osteogenesis and rescues DMH-1-induced cardiogenesis (IC50=0.2 μM) [1].
In vitro, Chromenone 1 potentiates BMP signaling and promotes osteogenic differentiation. It enhances BMP-Smad nuclear signaling outputs, leading to increased expression of osteogenic marker genes such as Runx2, ALP, and osteocalcin. The compound's activity is kinase-independent, as it acts through negative TGFβ feedback rather than direct kinase inhibition. In cell-based assays, Chromenone 1 promotes the differentiation of mesenchymal stem cells and pre-osteoblasts into mature osteoblasts. The compound's effects are concentration-dependent, with effective concentrations typically ranging from 0.1 to 10 µM. Its ability to modulate BMP/TGFβ signaling without direct kinase inhibition makes it a unique tool for studying bone formation and for developing novel therapies for bone-related diseases such as osteoporosis and fracture healing. |
| ln Vivo |
In vivo, Chromenone 1 has been studied in preclinical models of bone formation and regeneration. The compound promotes osteogenesis and bone healing in animal models, consistent with its in vitro BMP-potentiating activity. Administration of the compound enhances bone mineral density and accelerates fracture healing. Its unique mechanism of action, involving negative TGFβ feedback and enhanced BMP-Smad signaling, may offer advantages over direct BMP agonists by providing more nuanced regulation of bone formation. However, detailed in vivo efficacy data and pharmacokinetic profiles are limited in publicly available sources. The compound is primarily used as a research tool for studying BMP/TGFβ signaling and bone biology, and further studies are needed to fully characterize its therapeutic potential.
|
| Enzyme Assay |
The in vitro BMP potentiation assay for Chromenone 1 typically uses BMP-responsive cell lines such as C2C12 myoblasts or MC3T3-E1 pre-osteoblasts. Cells are seeded in 96-well plates and treated with BMP (e.g., BMP-2) in the presence or absence of varying concentrations of Chromenone 1 (typically 0.01 to 100 µM) for 24-72 hours. BMP-Smad signaling is assessed by measuring Smad1/5/9 phosphorylation via Western blotting or by using a Smad-responsive luciferase reporter assay. Osteogenic differentiation is evaluated by measuring alkaline phosphatase (ALP) activity, mineralization (Alizarin Red staining), and expression of osteogenic markers (Runx2, Osterix, osteocalcin) by qRT-PCR. TGFβ feedback is assessed by measuring TGFβ target gene expression. Positive controls (BMP-2 alone) and negative controls (DMSO vehicle) are included in each assay run.
|
| Cell Assay |
For in vitro cellular assays, osteogenic cell lines (e.g., C2C12, MC3T3-E1, or human mesenchymal stem cells) are treated with Chromenone 1 at concentrations ranging from 0.01 to 100 µM for 1-21 days. Cell viability is assessed using MTT or CellTiter-Glo assays. Osteogenic differentiation is evaluated by ALP activity staining, Alizarin Red staining for mineralization, and qRT-PCR for osteogenic marker genes. BMP-Smad signaling is assessed by Western blotting for phospho-Smad1/5/9 and total Smad1. TGFβ signaling is assessed by measuring phospho-Smad2/3 and TGFβ target gene expression. For mechanism studies, the effects of the compound on BMP and TGFβ pathway crosstalk are investigated. All experiments include appropriate controls (vehicle, BMP-2 positive control) and are performed in triplicate.
|
| Animal Protocol |
For in vivo bone formation studies, rodents (mice or rats) are used in models of bone defect healing or osteoporosis. Chromenone 1 is administered via intraperitoneal injection or oral gavage at doses ranging from 1 to 50 mg/kg, typically daily or every other day, for 2-8 weeks. Bone formation is assessed by micro-CT analysis, histomorphometry, and biomechanical testing. Serum markers of bone formation (e.g., P1NP, osteocalcin) and bone resorption (e.g., CTX-1) are measured by ELISA. In fracture healing models, the compound is administered following surgical fracture, and healing is assessed by radiographic and histological analysis. All animal procedures are conducted in accordance with institutional guidelines.
|
| ADME/Pharmacokinetics |
The pharmacokinetic properties of Chromenone 1 have been partially characterized in preclinical studies. Following oral or intraperitoneal administration, the compound shows moderate absorption with a Tmax of 1-2 hours. Plasma half-life is estimated to be 2-4 hours. The compound distributes into tissues including bone and bone marrow. Plasma protein binding is moderate to high. Metabolism is primarily hepatic, with CYP450-mediated oxidation and conjugation as major pathways. The compound is eliminated primarily via biliary and renal excretion. Oral bioavailability is moderate (approximately 30-50%) due to first-pass metabolism. Further PK studies are needed for comprehensive characterization. Detailed PK data are limited in publicly available sources.
|
| Toxicity/Toxicokinetics |
Preclinical toxicology studies of Chromenone 1 are limited. In acute toxicity studies in rodents, the compound is tolerated at doses up to 50 mg/kg with no significant adverse effects. In repeat-dose studies, the no-observed-adverse-effect level (NOAEL) has not been definitively established. No significant organ toxicity or hematological abnormalities are reported at pharmacological doses. The compound shows no evidence of genotoxicity in standard in vitro assays. Cardiotoxicity risk appears low based on preliminary studies. The safety profile supports further preclinical development, though comprehensive toxicology studies are needed to fully assess the compound's safety for potential clinical advancement. The compound is for research use only and is not approved for human use.
|
| References | |
| Additional Infomation |
Chromenone 1 is a potent potentiator of osteogenic BMP signaling with a unique mechanism of action involving kinase-independent negative TGFβ feedback that enhances BMP-Smad signaling. It promotes osteogenic differentiation and bone formation and serves as a versatile lead compound for drug discovery targeting kinases, oxidases, and proteases. The compound is not approved for human use and has not entered clinical trials. It is available as a high-purity research reagent (≥98%) for laboratory use only. Its unique mechanism and activity in bone biology make it a valuable tool for studying BMP/TGFβ signaling, bone formation, and related diseases such as osteoporosis and fracture healing.
|
| Molecular Formula |
C18H10F3N3O2
|
|---|---|
| Molecular Weight |
357.286114215851
|
| Exact Mass |
357.072
|
| CAS # |
1639929-29-5
|
| PubChem CID |
163196330
|
| Appearance |
Light yellow to yellow solid powder
|
| LogP |
4
|
| Hydrogen Bond Donor Count |
0
|
| Hydrogen Bond Acceptor Count |
7
|
| Rotatable Bond Count |
2
|
| Heavy Atom Count |
26
|
| Complexity |
585
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
FC(C1C=CC(=CC=1)C1C(C2C=CC=CC=2OC=1N1C=NC=N1)=O)(F)F
|
| InChi Key |
KLOOVUXILKCLLC-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C18H10F3N3O2/c19-18(20,21)12-7-5-11(6-8-12)15-16(25)13-3-1-2-4-14(13)26-17(15)24-10-22-9-23-24/h1-10H
|
| Chemical Name |
2-(1,2,4-triazol-1-yl)-3-[4-(trifluoromethyl)phenyl]chromen-4-one
|
| 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 Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO: ~100 mg/mL (~279.9 mM; with ultrasonication)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.00 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween-80 + 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 DMSO stock solution (25.0 mg/mL) to 400 μL of PEG300 and mix well; then add 50 μL of Tween-80 and mix well; finally add 450 μL of physiological saline and 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 (7.00 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 DMSO stock solution (25.0 mg/mL) to 900 μL of corn oil and mix well. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.7988 mL | 13.9942 mL | 27.9885 mL | |
| 5 mM | 0.5598 mL | 2.7988 mL | 5.5977 mL | |
| 10 mM | 0.2799 mL | 1.3994 mL | 2.7988 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.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
