TY-51469 displays 100% stability in pivoting at 40°C for up to 1 hour [1]. TY-51469 transcribes neutrophil buildup and decreases pivot fibrosis in mice [2].

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In a silica-induced pulmonary fibrosis mouse model, administration of TY-51469 at 1.0 mg/kg/day for 21 days significantly reduced the Ashcroft pathological fibrosis score and lung hydroxyproline content compared to the silica-only group. The compound also significantly reduced the total cell count and neutrophil number in bronchoalveolar lavage fluid (BALF), as well as the levels of macrophage inflammatory protein-2 (MIP-2), monocyte chemoattractant protein-1 (MCP-1), and transforming growth factor-β1 (TGF-β1) in BALF on day 21. [1]

Early administration of TY-51469 (days 0–11) resulted in a greater reduction of lung hydroxyproline content compared to late administration (days 12–21). Both early and late treatments significantly reduced BALF neutrophil counts. The expression of mouse mast cell protease-4 (mMCP-4) mRNA in lung tissue increased over time (days 7, 14, 21) after silica instillation. [1]

Male 8-week-old ICR mice were anesthetized with ether, and silica (10 mg per body in 100 μL saline) was administered intratracheally. TY-51469 was dissolved first in 100 mM NaOH, then diluted with 67 mM phosphate buffer to achieve final doses. An osmotic pump was filled with this solution and inserted into a subcutaneous pocket, releasing the drug continuously at a rate of 0.3 μL/h for 21 days at doses of 0.1 or 1.0 mg/kg/day. Mice were sacrificed 21 days after silica administration by cutting the abdominal aorta under anesthesia. For early vs. late administration, one group received TY-51469 (1.0 mg/kg) on days 0–11, another on days 12–21. A control group received saline only. [1]

Histopathological evaluation: The left lung was fixed with 10% formaldehyde neutral buffer solution at a transpulmonary pressure of 25 cm H₂O for at least 48 hours, embedded in paraffin, and 3-μm sections were stained with Azan-Mallory. Fibrosis severity was assessed semiquantitatively using the Ashcroft method. [1]

Hydroxyproline measurement: Whole lungs were desiccated overnight at 110°C, then digested in 6N HCl for 8 hours at 120°C, desiccated again for 6 hours at 120°C. Then citrate/acetate buffer and chloramine T solution were added, left at room temperature for 20 minutes, followed by Ehrlich's solution and incubation for 15 minutes at 65°C. Samples were cooled, spun at 3100 rpm for 5 minutes, and read at 550 nm. [1]

Bronchoalveolar lavage: After tracheal excision, a plastic cannula was inserted and lungs were washed 3 times with 2 mL saline. BALF was centrifuged at 1100 rpm for 10 minutes. Total cell count was determined with a hemocytometer; cell differentiation was examined by counting at least 200 cells on Wright-Giemsa-stained smears. Supernatants were stored at -80°C for cytokine measurement (MIP-2, MCP-1, TGF-β1 by ELISA). [1]

Quantitative RT-PCR: Lungs were harvested on days 0, 7, 14, 21; total RNA extracted using an RNeasy Mini Kit, reverse transcribed into cDNA. Real-time RT-PCR for mMCP-4 was performed using SYBR Green and a LightCycler thermal cycler system. Primers for mMCP-4 and GAPDH were used. PCR conditions: 95°C for 10 seconds, then 40 cycles of 95°C for 5 seconds and 60°C for 20 seconds. [1]

[1]. The specific chymase inhibitor TY-51469 suppresses the accumulation of neutrophils in the lung and reduces silica-induced pulmonary fibrosis in mice. Expert Opinion on Therapeutic Targets Volume 15, 2011 - Issue 4.

TY-51469 is a specific chymase inhibitor that does not inhibit other chymotrypsin-like serine proteases such as bovine chymotrypsin or human cathepsin G, even at a concentration of 10 μM. It significantly reduces chymase activity but does not affect ACE activity. In the silica-induced mouse lung fibrosis model, the compound suppresses fibrosis likely via reduction of MIP-2 and neutrophil accumulation, independent of angiotensin II formation (since mouse chymase does not produce cardiac angiotensin II). The compound’s inhibitory effects are stronger when administered early (days 0–11) compared to late administration (days 12–21), suggesting that prevention of early inflammatory cell infiltration suppresses the fibrotic process. [1]

C20H15FN2O6S4

526.6013

525.979

603987-59-3

9828275

Off-white to light brown solid powder

4.6

2

11

6

33

953

0

S(C1=C(C([H])([H])[H])C2C([H])=C(C([H])=C([H])C=2S1)F)(N([H])C1C([H])=C([H])C(C2=NC(C(=O)O[H])=C([H])S2)=C([H])C=1S(C([H])([H])[H])(=O)=O)(=O)=O

CBRCULCCRGSSLB-UHFFFAOYSA-N

InChI=1S/C20H15FN2O6S4/c1-10-13-8-12(21)4-6-16(13)31-20(10)33(28,29)23-14-5-3-11(7-17(14)32(2,26)27)18-22-15(9-30-18)19(24)25/h3-9,23H,1-2H3,(H,24,25)

2-(4-((5-fluoro-3-methylbenzo[b]thiophene)-2-sulfonamido)-3-(methylsulfonyl)phenyl)thiazole-4-carboxylic acid

TY-51469 TY 51469 TY51469 Related CAS#

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~33.33 mg/mL (~63.29 mM)

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.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*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).

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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)]
*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.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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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).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)