| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| 50mg |
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| 100mg |
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| Targets |
Mcl-1-PUMA Modulator-8 targets the protein-protein interaction between Mcl-1 and PUMA. Mcl-1 is an anti-apoptotic protein that binds to and inhibits pro-apoptotic proteins like PUMA. By modulating this interaction, the compound aims to release PUMA, allowing it to activate the apoptotic pathway and induce cell death in cancer cells. This is a strategy to overcome resistance to apoptosis.
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| ln Vitro |
CLZ-8 (compound 8) (0-160 μM, 48 h) strongly suppresses apoptosis that is dependent on PUMA [1]. In a dose-dependent way, CLZ-8 (0–1 μM, 2 hours) markedly increased the vitality of irradiation cells, considerably shielded HUVEC, and suppressed overexpressed PUMA [2]. Radiation-induced apoptosis is attenuated by CLZ-8 (0-1 μM, 24 hours) [2]. HUVEC is protected against DNA fragmentation by CLZ-8 (1 μM, 2 hours) [2].
In vitro, Mcl-1-PUMA Modulator-8 is characterized by its ability to disrupt the Mcl-1/PUMA interaction. Its activity can be assessed in biochemical assays measuring the binding of Mcl-1 to PUMA in the presence of the compound. In cellular assays, it promotes apoptosis in cancer cell lines that are dependent on Mcl-1 for survival. |
| ln Vivo |
Mice treated with CLZ-8 (0-400 mg/kg; ig; once) have strong anti-radiation effects [2].
In vivo, Mcl-1-PUMA Modulator-8 is used in research to study the effects of modulating the Mcl-1/PUMA interaction. It would be studied in animal models of cancer to assess its efficacy in inducing tumor cell apoptosis and inhibiting tumor growth. |
| Enzyme Assay |
In vitro enzyme/receptor binding studies for Mcl-1-PUMA Modulator-8 are performed using protein-protein interaction assays. In these assays, recombinant Mcl-1 and PUMA proteins are incubated in the presence of varying concentrations of the compound. The disruption of their binding is measured, and the IC50 value is calculated.
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| Cell Assay |
Apoptosis analysis[1][2]
Cell Types: DLD-1 cells or HUVEC Cell Tested Concentrations: 0-160 μM (DLD-1) or 0.01, 0.1 and 1 μM (HUVEC) Incubation Duration: 48 hrs (hours) (DLD-1 ) or 24 hrs (hours) (HUVEC) Experimental Results: Dramatically inhibited PUMA-dependent apoptosis with an IC50 of 38.93 ± 0.91 μM. Attenuates radiation-induced apoptosis. Western Blot Analysis [2] Cell Types: HUVEC Cell Tested Concentrations: 0.001, 0.01, 0.1 and 1 μM Incubation Duration: 2 h Experimental Results: PUMA induction was inhibited and p53 levels were Dramatically diminished after radiation. Dramatically diminished MCL-1 levels and increased Bcl-XL levels. In vitro cellular assays for Mcl-1-PUMA Modulator-8 are used to study its effects on cancer cells. Cells are treated with the compound, and key readouts include apoptosis (Annexin V/PI staining), cell viability (MTT or CellTiter-Glo assays), and the levels of Mcl-1 and PUMA. |
| Animal Protocol |
Animal/Disease Models: 6-8 weeks old male balb/c (Bagg ALBino) mouse [2]
Doses: 100, 200 and 400 mg/kg Route of Administration: intragastric (po) (po)administration once 30 minutes before irradiation. Experimental Results: Improved survival rate of irradiated mice. In vivo animal studies for Mcl-1-PUMA Modulator-8 are conducted in xenograft models. Tumor-bearing mice are treated with the compound, and tumor growth inhibition and apoptosis induction are measured. |
| ADME/Pharmacokinetics |
Pharmacokinetic properties of Mcl-1-PUMA Modulator-8 are not detailed in the provided sources. It has a CAS number of 678158-55-9.
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| Toxicity/Toxicokinetics |
Mcl-1-PUMA Modulator-8 is a research compound and is not intended for human use. Its safety profile would be evaluated in preclinical studies. Specific toxicity data are not provided.
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| References | |
| Additional Infomation |
Mcl-1-PUMA Modulator-8 is a research-use-only compound that modulates the Mcl-1/PUMA interaction to promote apoptosis. Its CAS number is 678158-55-9. It is used to study apoptosis and cancer biology. It is not an approved drug.
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| Molecular Formula |
C22H23N3O2S
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|---|---|
| Molecular Weight |
393.5019
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| Exact Mass |
393.151
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| CAS # |
678158-55-9
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| PubChem CID |
988971
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
3.2
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
28
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| Complexity |
599
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| Defined Atom Stereocenter Count |
0
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| SMILES |
S1/C(=C(/[H])\C2C([H])=C([H])C(C3C([H])=C([H])C([H])=C([H])C=3[H])=C([H])C=2[H])/C(N=C1N1C([H])([H])C([H])([H])N(C([H])([H])C([H])([H])O[H])C([H])([H])C1([H])[H])=O
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| InChi Key |
IBEWMFVUBLAYJT-SILNSSARSA-N
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| InChi Code |
InChI=1S/C22H23N3O2S/c26-15-14-24-10-12-25(13-11-24)22-23-21(27)20(28-22)16-17-6-8-19(9-7-17)18-4-2-1-3-5-18/h1-9,16,26H,10-15H2/b20-16-
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| Chemical Name |
(5Z)-2-[4-(2-hydroxyethyl)piperazin-1-yl]-5-[(4-phenylphenyl)methylidene]-1,3-thiazol-4-one
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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 : ~50 mg/mL (~127.06 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 0.83 mg/mL (2.11 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 8.3 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 | 2.5413 mL | 12.7065 mL | 25.4130 mL | |
| 5 mM | 0.5083 mL | 2.5413 mL | 5.0826 mL | |
| 10 mM | 0.2541 mL | 1.2706 mL | 2.5413 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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