| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
Dazcapistat targets calpain 1 (μ-calpain), calpain 2 (m-calpain), and calpain 9, three members of the calpain family of calcium-dependent cysteine proteases. The compound demonstrates potent inhibitory activity against all three targets with IC50 values of <3 µM. Calpains are involved in various cellular processes including cytoskeletal remodeling, cell migration, apoptosis, and inflammatory signaling. By inhibiting calpain activity, Dazcapistat modulates these processes and reduces fibrotic responses.
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| ln Vitro |
In vitro, Dazcapistat demonstrates potent inhibition of calpain 1, calpain 2, and calpain 9 with IC50 values of <3 µM. The compound reduces the expression and production of IL-6 in injured lung tissue, indicating anti-inflammatory activity. Dazcapistat shows concentration-dependent inhibition of calpain activity in biochemical assays using purified enzyme preparations. The compound's effects on calpain-mediated signaling pathways and inflammatory responses have been characterized in various cellular models.
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| ln Vivo |
In vivo, Dazcapistat has been evaluated in animal models of lung injury and fibrosis. The compound is orally active and reduces IL-6 expression in injured lung tissue. Dazcapistat alleviates fibrosis in preclinical models, demonstrating its therapeutic potential for fibrotic diseases. The compound's oral bioavailability and efficacy in animal models support its continued development as a therapeutic agent for pulmonary fibrosis and other fibrotic conditions.
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| Enzyme Assay |
The in vitro enzyme inhibition assay for Dazcapistat typically involves measuring the activity of purified calpain 1, calpain 2, or calpain 9 using a fluorogenic peptide substrate in the presence of calcium ions. Purified enzyme is incubated with varying concentrations of Dazcapistat (0.001-100 µM) in assay buffer containing calcium at 25-37°C for 15-30 minutes. The reaction is initiated by adding the substrate, and fluorescence is measured continuously. IC50 values are calculated from dose-response curves.
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| Cell Assay |
For in vitro cell-based assays, cells such as lung fibroblasts or epithelial cells are cultured and treated with Dazcapistat at concentrations ranging from 0.1-100 µM for 24-72 hours. Calpain activity is measured in cell lysates using a calpain activity assay kit. IL-6 and other inflammatory cytokine levels are measured by ELISA. Fibrosis markers such as collagen and fibronectin are assessed by Western blot or qPCR. Cell viability and proliferation are assessed using MTT or CCK-8 assays.
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| Animal Protocol |
In vivo animal studies for Dazcapistat are conducted using models of lung injury and fibrosis, such as bleomycin-induced pulmonary fibrosis in mice. Dazcapistat is administered orally at doses ranging from 1-100 mg/kg daily or twice daily for 1-3 weeks. Lung tissue is collected for histopathological analysis of fibrosis. IL-6 and other inflammatory markers are measured in lung tissue and bronchoalveolar lavage fluid by ELISA. Calpain activity is assessed in tissue lysates.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of Dazcapistat have been characterized. The compound shows good oral bioavailability. Molecular weight is 395.38 and molecular formula is C₂₁H₁₈FN₃O₄. CAS number is 2221010-42-8. Detailed pharmacokinetic parameters such as half-life, Cmax, and protein binding are available from the primary literature. The compound should be stored under recommended conditions.
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| Toxicity/Toxicokinetics |
Toxicology data for Dazcapistat are limited. As a research compound, it has not been fully evaluated for safety. The compound's mechanism of calpain inhibition suggests potential effects on various cellular processes that would require careful safety assessment. Standard toxicological endpoints including body weight, organ weights, clinical chemistry, and histopathology should be evaluated. The compound is intended for research use only and is not approved for human use.
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| References | |
| Additional Infomation |
Dazcapistat (BLD-2660) is an orally active calpain inhibitor with IC50 values of <3 µM for calpain 1, calpain 2, and calpain 9. The compound reduces IL-6 expression and alleviates fibrosis in preclinical models. Dazcapistat has potential therapeutic applications for fibrotic diseases, particularly pulmonary fibrosis. It is intended for research use only and is not approved for clinical use.
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| Molecular Formula |
C21H18FN3O4
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|---|---|
| Molecular Weight |
395.38
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| Exact Mass |
395.128
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| CAS # |
2221010-42-8
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| PubChem CID |
134397000
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| Appearance |
White to off-white solid powder
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| LogP |
2.9
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
29
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| Complexity |
611
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O1C(C(NC(CC2=CC=CC=C2)C(=O)C(N)=O)=O)=C(C2=CC=CC=C2F)N=C1C
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| InChi Key |
XYQHCMDVGIJOTA-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C21H18FN3O4/c1-12-24-17(14-9-5-6-10-15(14)22)19(29-12)21(28)25-16(18(26)20(23)27)11-13-7-3-2-4-8-13/h2-10,16H,11H2,1H3,(H2,23,27)(H,25,28)
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| Chemical Name |
N-(4-amino-3,4-dioxo-1-phenylbutan-2-yl)-4-(2-fluorophenyl)-2-methyl-1,3-oxazole-5-carboxamide
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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: 100 mg/mL (252.92 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.32 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 (6.32 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. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (6.32 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5292 mL | 12.6461 mL | 25.2921 mL | |
| 5 mM | 0.5058 mL | 2.5292 mL | 5.0584 mL | |
| 10 mM | 0.2529 mL | 1.2646 mL | 2.5292 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.
Link: https://clinicaltrials.gov/ct2/show/NCT04334460
Conditions:Sars-CoV-2|Covid19Link: https://clinicaltrials.gov/ct2/show/NCT04244825
Conditions:Idiopathic Pulmonary FibrosisLink: https://clinicaltrials.gov/ct2/show/NCT04001998
Conditions:Fibrosis
Title:First in Human Study in Healthy Volunteers Followed With Dosing in Participants With Lung or Liver Fibrosis
Status:Completed
updateDate:2020-03-19
Ctid:NCT03559166
Link: https://clinicaltrials.gov/ct2/show/NCT03559166
Conditions:FibrosisProducts are for research use only; We do not sell to patients
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