| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Targets |
BI-4394 targets matrix metalloproteinase-13 (MMP-13), an enzyme that plays a key role in the degradation of type II collagen, the major structural protein in articular cartilage. MMP-13 is a zinc-dependent endopeptidase that is upregulated in osteoarthritis, leading to cartilage erosion and joint destruction. BI-4394 is a potent and selective inhibitor of MMP-13, with an IC50 of 1 nM. By inhibiting MMP-13, BI-4394 may prevent cartilage degradation and slow the progression of osteoarthritis.
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| ln Vitro |
BI-4394 (Compound 15) exhibits potency (11 nM) in the full-length MMP-13 collagen degradation assay and has an IC50 of 31 nM for inhibiting the breakdown of bovine nasal cartilage. MMP-2, MMP-9, MMP-10, and MMP-14 are all inhibited by BI-4394, with IC50 values of 18, 8.9, 16, and 8.3 μM, respectively[1].
In vitro, BI-4394 is a potent and selective inhibitor of MMP-13. It inhibits the recombinant human enzyme with an IC50 of 0.001 µM (1 nM). The compound is highly selective for MMP-13, showing >1000-fold selectivity over other MMPs. For example, its IC50 values against MMP-1, -2, -3, -7, -8, -9, -10, -12, and -14 range from 8.3 to greater than 22 µM. This high selectivity is crucial for minimizing off-target effects and is a key feature of its potential as a therapeutic agent. |
| ln Vivo |
Compound 15, BI-4394, demonstrated micromolar plasma levels (AUC=1109±64 nM h/mL) and modest clearance (CL=34 mL /min/kg) with an acceptable bioavailability (39%). The drug's Vss is relatively low, measuring 0.26 mL/mi/kg on the Rat Pharmacokinetic Curve. In rats, BI-4394 had a short terminal elimination half-life (t1/2=0.47 hours) when administered orally at 10 mg/kg or intravenously at 1 mg/kg [1].
In vivo, BI-4394 has been developed as an orally active compound for the potential treatment of osteoarthritis. While specific in vivo efficacy data, such as results from animal models of osteoarthritis, are not detailed in standard product descriptions, its potent and selective inhibition of MMP-13 suggests it could be effective in preventing cartilage degradation. Its oral bioavailability makes it a suitable candidate for chronic administration. |
| Enzyme Assay |
In vitro enzyme assays for BI-4394 measure its inhibition of MMP-13 activity. Recombinant human MMP-13 is activated and incubated with a fluorogenic peptide substrate in the presence of varying concentrations of the compound. The cleavage of the substrate produces a fluorescent signal that is measured over time. The IC50 is determined from the dose-response curve. Selectivity is assessed by testing the compound against a panel of other MMPs, including MMP-1, -2, -3, -7, -8, -9, -10, -12, and -14.
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| Cell Assay |
In vitro cell-based assays for BI-4394 are used to study its effects on cartilage degradation. Chondrocytes or cartilage explants are treated with the compound and then stimulated with inflammatory cytokines to induce MMP-13 expression. The degradation of type II collagen is measured by assessing the release of collagen fragments or by using specific antibodies. The compound's ability to protect cartilage from degradation is assessed. These assays confirm the compound's activity in a cellular context.
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| Animal Protocol |
Animal/Disease Models: Srapgue Dally rat[1]
Doses: 10 mg/kg (po (oral gavage)); 1 mg/kg (iv) Route of Administration: oral (10 mg/kg); iv (1 mg/kg) (drug Metabokinetic analysis) Experimental Results: T1/2=0.47 h in rats (1 mg/kg, intravenous (iv) (iv)injection) and rats (10 mg/kg, oral administration) respectively. In vivo animal experiments for BI-4394 would be conducted in animal models of osteoarthritis. In a typical study, the compound is administered orally to animals with induced osteoarthritis, and the progression of cartilage degradation is assessed. Parameters such as cartilage thickness, proteoglycan loss, and collagen degradation are measured. These studies would provide evidence for the in vivo efficacy of BI-4394. However, specific protocols are not detailed in standard product descriptions. |
| ADME/Pharmacokinetics |
BI-4394 has a CAS number of 1222173-37-6. The chemical name is 4-[[[5-(2-ethoxycarbonyl-1H-indol-5-yl)-1-methylpyrazole-3-carbonyl]amino]methyl]benzoic acid. It is a solid compound. For storage, it is recommended to keep the powder at -20°C. Detailed pharmacokinetic properties such as absorption, distribution, metabolism, and excretion (ADME) have been characterized. BI-4394 is orally active.
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| Toxicity/Toxicokinetics |
Detailed toxicity data for BI-4394 is not provided in standard product descriptions. As a research compound, its toxicity profile has not been extensively characterized. BI-4394 is a selective MMP-13 inhibitor, and its toxicity would be related to its effects on MMP-13-mediated processes in normal tissues. However, comprehensive toxicological studies have not been reported. As with all research chemicals, standard laboratory safety precautions should be followed when handling BI-4394. Its use is limited to research applications.
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| References |
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| Additional Infomation |
BI-4394 (MMP13-IN-3) is a research compound and is not approved for any clinical or therapeutic use. It is a potent, selective, and orally active inhibitor of MMP-13. BI-4394 inhibits MMP-13 with an IC50 of 1 nM and is highly selective over other MMPs. It has been developed for the potential treatment of osteoarthritis. Its mechanism of action involves inhibiting MMP-13, thereby preventing cartilage degradation. BI-4394 is a valuable research tool for studying the role of MMP-13 in osteoarthritis and other diseases.
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| Molecular Formula |
C24H22N4O5
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| Molecular Weight |
446.46
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| Exact Mass |
446.159
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| CAS # |
1222173-37-6
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| PubChem CID |
45376872
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| Appearance |
White to off-white solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
764.4±60.0 °C at 760 mmHg
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| Flash Point |
416.1±32.9 °C
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| Vapour Pressure |
0.0±2.7 mmHg at 25°C
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| Index of Refraction |
1.668
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| LogP |
3.16
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
33
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| Complexity |
726
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CCOC(=O)C1=CC2=C(N1)C=CC(=C2)C3=CC(=NN3C)C(=O)NCC4=CC=C(C=C4)C(=O)O
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| InChi Key |
MMJPVSDTLGFIQW-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C24H22N4O5/c1-3-33-24(32)20-11-17-10-16(8-9-18(17)26-20)21-12-19(27-28(21)2)22(29)25-13-14-4-6-15(7-5-14)23(30)31/h4-12,26H,3,13H2,1-2H3,(H,25,29)(H,30,31)
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| Chemical Name |
4-[[[5-(2-ethoxycarbonyl-1H-indol-5-yl)-1-methylpyrazole-3-carbonyl]amino]methyl]benzoic acid
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| Synonyms |
BI-4394 BI 4394 BI4394
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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 (~223.98 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 | 2.2398 mL | 11.1992 mL | 22.3984 mL | |
| 5 mM | 0.4480 mL | 2.2398 mL | 4.4797 mL | |
| 10 mM | 0.2240 mL | 1.1199 mL | 2.2398 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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