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| Targets |
TD-198946 is a small molecule that promotes chondrogenic differentiation and cartilage regeneration. It enhances chondrocyte differentiation and cartilage matrix production by upregulating cartilage-related genes such as SOX9. TD-198946 exerts its effect through the regulation of Runx1 expression. It is a disease-modifying osteoarthritis compound that effectively repairs cartilage and halts osteoarthritis progression.
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| ln Vitro |
TD-198946 possesses strong chondrogenic properties. Without encouraging hypertrophy of cell and metatarsal organ cultures, TD-198946 substantially stimulates chondrogenic differentiation. In ATDC5 cells, TD-198946 produces a higher level of Col2a1 promoter activity than insulin. TD-198946 activates endogenous chondrocyte markers Col2a1 and Acan in C3H10T1/2 cells, ATDC5 cells, and primary mouse chondrocytes in a dose-dependent manner, with peak effects occurring at 1–10 μM [1].
In vitro, TD-198946 strongly induces chondrogenic differentiation without promoting hypertrophy in cell and metatarsal organ cultures. In ATDC5 cells, TD-198946 induces Col2a1 promoter activity more strongly than insulin. It enhances chondrocyte differentiation and cartilage matrix production by upregulating cartilage-related genes such as SOX9. Its in vitro activity is characterized by potent induction of chondrogenesis. |
| ln Vivo |
Direct injection of TD-198946 into the joint space effectively stops and reverses articular cartilage deterioration. In comparison to normal tissue, the expression of Runx1 is downregulated in both human and mouse OA cartilage [1], which is how TD-198946 works. In chronic osteoarthritis, TD-198946 has actions that affect the course of the illness. TD-198946 may be the most effective treatment in the early or intermediate stages of osteoarthritis, before the articular cartilage has entirely degraded, as it may stop the evolution of the condition by working on residual chondrocytes rather than replacing damaged cartilage. [2]. Human mesenchymal stem cells and mouse and canine costal chondrocytes were cultured on temperature-responsive culture plates using TD-198946 to create chondrocyte sheets. After that, the transplanted cell sheets were effectively utilized to encourage long-term cartilage remodeling, and knee cartilage defects in dogs and mice showed no signs of chondrocyte hypertrophy [3].
In vivo, TD-198946 has been shown to promote chondrogenesis of several stem cells. It effectively repairs cartilage and halts osteoarthritis progression in disease models. Cell-sheet technology combined with TD-198946 has been used for cartilage regeneration. Its in vivo efficacy is attributed to its ability to promote chondrogenic differentiation and cartilage matrix production. TD-198946 is a disease-modifying osteoarthritis compound. |
| Enzyme Assay |
In vitro enzyme/receptor binding assays are not typical for TD-198946, as it acts by modulating gene expression and signaling pathways rather than binding to specific enzymes. However, its effects on SOX9 and Runx1 expression can be assessed using qPCR or Western blotting. These assays provide insights into its mechanism of action as a chondrogenic agent.
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| Cell Assay |
In vitro cellular assays for TD-198946 typically involve treating chondrogenic cell lines such as ATDC5 with the compound and measuring chondrogenic differentiation markers such as Col2a1 promoter activity. TD-198946 induces Col2a1 promoter activity more strongly than insulin in ATDC5 cells. It strongly induces chondrogenic differentiation without promoting hypertrophy in cell and metatarsal organ cultures. These cell-based studies demonstrate its potent chondrogenic activity.
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| Animal Protocol |
In vivo animal models for TD-198946 include models of osteoarthritis or cartilage injury to evaluate its efficacy in cartilage repair. The compound is administered by appropriate routes, and cartilage regeneration and osteoarthritis progression are assessed. TD-198946 effectively repairs cartilage and halts osteoarthritis progression. It has been shown to promote chondrogenesis of several stem cells.
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| ADME/Pharmacokinetics |
TD-198946 has a molecular weight of 470.5 and a molecular formula of C25H18N4O4S. Its CAS number is 364762-86-7. The compound is a thienoindazole derivative. It is a potent chondrogenic agent that strongly induces chondrogenic differentiation without promoting hypertrophy. TD-198946 is a disease-modifying osteoarthritis compound.
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| Toxicity/Toxicokinetics |
TD-198946 is a chondrogenic agent with a well-characterized mechanism of action. As with any compound that modulates cell differentiation, potential toxicity may include effects on normal tissue development and function. The compound's safety profile should be evaluated in preclinical toxicology studies. TD-198946 is for research use only and is not approved for human therapeutic use. It represents a valuable tool for studying chondrogenesis and osteoarthritis.
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| References |
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| Additional Infomation |
TD-198946 (CAS# 364762-86-7) is a potent chondrogenic agent and a thienoindazole derivative. It strongly induces chondrogenic differentiation without promoting hypertrophy. TD-198946 enhances chondrocyte differentiation and cartilage matrix production by upregulating SOX9 and regulates Runx1 expression. The compound is for research use only and not for human therapeutic use.
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| Molecular Formula |
C27H22N4O3S
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| Molecular Weight |
482.56
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| Exact Mass |
482.141
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| CAS # |
364762-86-7
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| PubChem CID |
9826550
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| Appearance |
White to light yellow solid powder
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| LogP |
5.965
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
35
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| Complexity |
750
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CN1C2=C(CCC3=C(SC(=C32)OC4=CC=C(C=C4)OCC5=NC6=CC=CC=C6C=C5)C(=O)N)C=N1
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| InChi Key |
QGAMAWMLTUNPAB-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C27H22N4O3S/c1-31-24-17(14-29-31)7-13-21-23(24)27(35-25(21)26(28)32)34-20-11-9-19(10-12-20)33-15-18-8-6-16-4-2-3-5-22(16)30-18/h2-6,8-12,14H,7,13,15H2,1H3,(H2,28,32)
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| Chemical Name |
1-methyl-8-[4-(quinolin-2-ylmethoxy)phenoxy]-4,5-dihydrothieno[3,4-g]indazole-6-carboxamide
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| Synonyms |
TD198946; TD 198946; TD-198946
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
DMSO : ≥ 28 mg/mL (~58.03 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0723 mL | 10.3614 mL | 20.7228 mL | |
| 5 mM | 0.4145 mL | 2.0723 mL | 4.1446 mL | |
| 10 mM | 0.2072 mL | 1.0361 mL | 2.0723 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.
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