| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg | |||
| 50mg | |||
| Other Sizes |
| Targets |
Mitochondrial F1F0-ATPase (specifically the OSCP subunit) and the Bcl-2 family proteins (Bax and Bak). Bz-423 activates Bax and Bak to induce mitochondrial outer membrane permeabilization and cytochrome c release. Bz-423 induces controlled superoxide generation, triggering redox-regulated apoptosis in pathogenic lymphocytes without broad-spectrum immune suppression.
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|---|---|
| ln Vitro |
Ramos B cells are rapidly killed by Bz-423, which also increases the superoxide response in Ramos cells. In Ramos cells, Bz-423 activates Bak and Bax but not ASK1/JNK. By altering Mcl-1 expression and functionally activating BH3-only proteins, Bz-423-induced superoxide in Ramos cells activates Bax and Bak [1]. Superoxide levels in MEFs are quickly raised by Bz-423 within an hour, and the extent of the increase depends on the concentration. The apoptosis caused by Bz-423 is dependent on superoxide [2].
Bz-423 induces apoptosis by activating Bax and Bak to induce mitochondrial outer membrane permeabilization and cytochrome c release. In Ramos cells, Bz-423 triggers the activation of Bax and Bak without concurrently activating ASK1/JNK. The induction of apoptosis relies on superoxide, and Bz-423 elicits a heightened superoxide response in these cells. In MEFs, Bz-423 rapidly elevates superoxide levels within 1 hour in a concentration-dependent manner. Bz-423 shows 2.3-fold greater potency against Ramos B cells (LC50 = 22 μM) compared to PBR ligands. |
| ln Vivo |
In vivo, Bz-423 shows partial activity in a mouse model of lupus. It has demonstrated potential as an anticancer agent by effectively targeting multidrug-resistant melanoma cells. Additionally, Bz-423 has shown promise in the treatment of graft-versus-host disease by selectively inducing apoptosis in alloreactive T cells. Bz-423 rescues mitochondrial membrane potential and neurite degeneration in SPG7 patient-derived neurons.
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| Enzyme Assay |
In vitro enzyme assays for Bz-423 involve measuring its binding to the OSCP subunit of mitochondrial F1F0-ATPase and its effects on ATPase activity. The compound's ability to induce superoxide generation can be measured using fluorescent probes such as MitoSOX. Bz-423 shows IC50 > 100 μM against PBR, confirming its selectivity for the mitochondrial F1F0-ATPase over the peripheral benzodiazepine receptor.
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| Cell Assay |
In vitro cellular assays for Bz-423 involve treating cells (such as Ramos B cells, MEFs, or SPG7 patient-derived neurons) with the compound and measuring apoptosis, superoxide generation, and mitochondrial membrane potential. Ramos B cells are rapidly killed by Bz-423. Apoptosis is assessed by measuring cytochrome c release, caspase activation, and cell viability. Superoxide levels are measured using fluorescent probes. LC50 values are determined from concentration-response curves.
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| Animal Protocol |
In vivo animal studies for Bz-423 typically involve administration to mouse models of lupus, graft-versus-host disease, or cancer. Bz-423 shows partial activity in a mouse model of lupus. In graft-versus-host disease models, Bz-423 selectively induces apoptosis in alloreactive T cells. Efficacy is assessed by measuring disease severity, immune cell populations, and survival. Pharmacokinetic parameters are determined from serial blood sampling.
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| ADME/Pharmacokinetics |
Pharmacokinetic data for Bz-423 is limited. The compound is soluble in DMSO at 80 mg/mL (181.44 mM). For in vivo administration, Bz-423 can be formulated in 10% DMSO + 40% PEG300 + 5% Tween 80 + 45% Saline at 3.3 mg/mL (7.48 mM). The compound should be stored at low temperature, with powder stable at -20°C for 3 years and in solvent at -80°C for 1 year.
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| Toxicity/Toxicokinetics |
Preclinical toxicity studies of Bz-423 are limited but suggest a favorable safety profile. The compound induces apoptosis in pathogenic lymphocytes without broad-spectrum immune suppression. Bz-423 shows 2.3-fold greater potency against Ramos B cells (LC50 = 22 μM) compared to PBR ligands, indicating selectivity for its target. The compound rescues mitochondrial membrane potential and neurite degeneration in SPG7 patient-derived neurons. Comprehensive toxicological evaluation is needed.
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| References | |
| Additional Infomation |
Bz-423 is a synthetic 1,4-benzodiazepine derivative that functions as an allosteric modulator of mitochondrial F1F0-ATPase by binding to the OSCP subunit. It induces apoptosis by activating Bax and Bak, leading to mitochondrial outer membrane permeabilization and cytochrome c release. Bz-423 has shown promise in the treatment of lupus, graft-versus-host disease, and multidrug-resistant melanoma. The compound is a valuable research tool for studying mitochondrial function and apoptosis.
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| Molecular Formula |
C27H21CLN2O2
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|---|---|
| Molecular Weight |
440.92
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| Exact Mass |
440.129
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| CAS # |
216691-95-1
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| PubChem CID |
644335
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.318g/cm3
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| Boiling Point |
737.5ºC at 760 mmHg
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| Flash Point |
399.8ºC
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| Vapour Pressure |
1.29E-21mmHg at 25°C
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| Index of Refraction |
1.682
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| LogP |
5.47
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
32
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| Complexity |
704
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
HIJCSNHREFFOML-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C27H21ClN2O2/c1-30-25-13-10-21(28)16-23(25)26(19-8-11-22(31)12-9-19)29-24(27(30)32)15-17-6-7-18-4-2-3-5-20(18)14-17/h2-14,16,24,31H,15H2,1H3
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| Chemical Name |
7-chloro-5-(4-hydroxyphenyl)-1-methyl-3-(naphthalen-2-ylmethyl)-3H-1,4-benzodiazepin-2-one
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| Synonyms |
Bz423; Bz 423; Bz-423
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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 : ≥ 125 mg/mL (~283.50 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.72 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 20.8 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: ≥ 2.08 mg/mL (4.72 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 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2680 mL | 11.3399 mL | 22.6799 mL | |
| 5 mM | 0.4536 mL | 2.2680 mL | 4.5360 mL | |
| 10 mM | 0.2268 mL | 1.1340 mL | 2.2680 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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