| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg | |||
| Other Sizes |
| Targets |
MZP-55 targets BET proteins BRD4, BRD3, and BRD2, which play crucial roles in regulating gene expression. As a PROTAC-based degrader, MZP-55 binds to both BRD4 BD2 (Kd = 8 nM) and the VHL-EloC-EloB protein (VCB) (Kd = 105 +/- 24 nM). By recruiting BRD3/4 to the VHL E3 ubiquitin ligase, MZP-55 induces ubiquitination and subsequent proteasomal degradation of these BET proteins. This mechanism leads to selective degradation of BRD3/4 and modulation of gene expression.
|
|---|---|
| ln Vitro |
Based on PROTAC technology, MZP-55 is a BRD3/4 selective degrader with a Kd of 8 nM for Brd4BD2. With a Kd of 105 ± 24 nM, MZP-55 binds to the VHL-EloC-EloB protein (VCB). MV4;11 and HL60 cells are inhibited by MZP-55, with pEC50 values of 7.31 ± 0.03 and 6.57 ± 0.02, respectively [1].
In vitro, MZP-55 binds to BRD4 BD2 with a Kd of 8 nM and to VHL-EloC-EloB protein with a Kd of 105 +/- 24 nM. The compound reduces BET protein levels in HeLa cells with pDC50 values of 8.1 for BRD4 (Dmax = 95%) and 7.7 for BRD3 (Dmax = 92%). MZP-55 shows inhibitory activity against MV4;11 and HL60 cells, with pEC50 values of 7.31 +/- 0.03 and 6.57 +/- 0.02, respectively. These in vitro data demonstrate the compound's potent degradation of BET proteins and antiproliferative activity. |
| ln Vivo |
Detailed in vivo activity data for MZP-55 are not extensively documented in publicly available literature. As a PROTAC-based degrader of BRD3/4, MZP-55 is being investigated for its potential in cancer therapy. By selectively degrading BRD3/4, the compound modulates the expression of oncogenes such as MYC, which are frequently dysregulated in cancer. Further in vivo studies are needed to fully characterize its therapeutic potential. MZP-55 is for research purposes only.
|
| Enzyme Assay |
MZP-55 is not typically used in standard receptor binding assays. Its activity is assessed through cell-based degradation assays measuring BET protein levels. In these assays, cells are treated with MZP-55 at varying concentrations for defined time periods. BET protein levels (BRD2, BRD3, BRD4) are assessed by Western blot. The extent of degradation is quantified by densitometry, and pDC50 values (negative log of the concentration required for 50% degradation) and Dmax values (maximum degradation) are calculated.
|
| Cell Assay |
Cellular assays for MZP-55 are performed using cancer cell lines such as HeLa, MV4;11, and HL60 cells. Cells are cultured in appropriate media and treated with MZP-55 at varying concentrations for defined time periods (e.g., 24 hours). BET protein levels are assessed by Western blot using antibodies against BRD2, BRD3, and BRD4. Cell viability and proliferation are assessed using standard assays such as MTT, CellTiter-Glo, or colony formation assays. pEC50 values for inhibition of cell growth are calculated from concentration-response curves.
|
| Animal Protocol |
In vivo studies with MZP-55 are conducted in mouse xenograft models using cancer cell lines sensitive to BET degradation, such as MV4;11 or HL60 cells. MZP-55 is administered via appropriate routes (e.g., intraperitoneal or intravenous) at defined doses and schedules. Tumor growth is monitored by caliper measurements, and tumor volumes are calculated. Tumor tissues are collected for assessment of BET protein levels by Western blot or immunohistochemistry. Pharmacokinetic parameters are determined from plasma samples collected at various time points.
|
| ADME/Pharmacokinetics |
MZP-55 has a molecular weight of 781.9 and a molecular formula of C39H44ClN7O6S. The compound is a PROTAC-based degrader that binds to BRD4 BD2 with a Kd of 8 nM. Detailed pharmacokinetic data for MZP-55 are not extensively documented in publicly available literature. The compound is soluble in DMSO. It should be stored at -20degC. MZP-55 is intended for research use only.
|
| Toxicity/Toxicokinetics |
Comprehensive toxicology data for MZP-55 are not extensively documented in publicly available sources. The compound is intended for research use only and is not approved for human therapeutic applications. Standard laboratory safety practices should be followed when handling this compound, including the use of appropriate personal protective equipment and adherence to institutional biosafety and chemical hygiene guidelines. The compound has a purity of ≥98%.
|
| References | |
| Additional Infomation |
MZP-55 is a selective degrader of BRD3/4 based on PROTAC technology. It binds to BRD4 BD2 with a Kd of 8 nM and to VHL-EloC-EloB protein with a Kd of 105 +/- 24 nM. MZP-55 reduces BET protein levels in human cells, with pDC50 values of 8.1 for BRD4 and 7.7 for BRD3, achieving Dmax values of 95% and 92%, respectively. The compound shows activity against MV4;11 and HL60 cells. MZP-55 is for research purposes only.
|
| Molecular Formula |
C57H70CLN7O10S
|
|---|---|
| Molecular Weight |
1080.72461271286
|
| Exact Mass |
1079.459
|
| CAS # |
2010159-48-3
|
| PubChem CID |
122539896
|
| Appearance |
White to off-white solid powder
|
| LogP |
6.4
|
| Hydrogen Bond Donor Count |
5
|
| Hydrogen Bond Acceptor Count |
13
|
| Rotatable Bond Count |
25
|
| Heavy Atom Count |
76
|
| Complexity |
1840
|
| Defined Atom Stereocenter Count |
5
|
| SMILES |
ClC1C=CC(=CC=1)N[C@H]1C2C=C(C3C=CC(C(NCCOCCOCCOCCOCC(N[C@H](C(N4C[C@@H](C[C@H]4C(NCC4C=CC(C5=C(C)N=CS5)=CC=4)=O)O)=O)C(C)(C)C)=O)=O)=CC=3)C=CC=2N(C(C)=O)[C@@H](C)C1
|
| InChi Key |
UHWNJFZTYJNBAN-HYXXSBGTSA-N
|
| InChi Code |
InChI=1S/C57H70ClN7O10S/c1-36-29-48(62-45-18-16-44(58)17-19-45)47-30-43(15-20-49(47)65(36)38(3)66)40-11-13-42(14-12-40)54(69)59-21-22-72-23-24-73-25-26-74-27-28-75-34-51(68)63-53(57(4,5)6)56(71)64-33-46(67)31-50(64)55(70)60-32-39-7-9-41(10-8-39)52-37(2)61-35-76-52/h7-20,30,35-36,46,48,50,53,62,67H,21-29,31-34H2,1-6H3,(H,59,69)(H,60,70)(H,63,68)/t36-,46+,48+,50-,53+/m0/s1
|
| Chemical Name |
(2S,4R)-1-[(2S)-2-[[2-[2-[2-[2-[2-[[4-[(2S,4R)-1-acetyl-4-(4-chloroanilino)-2-methyl-3,4-dihydro-2H-quinolin-6-yl]benzoyl]amino]ethoxy]ethoxy]ethoxy]ethoxy]acetyl]amino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
DMSO : ~50 mg/mL (~46.27 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (2.31 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.9253 mL | 4.6265 mL | 9.2530 mL | |
| 5 mM | 0.1851 mL | 0.9253 mL | 1.8506 mL | |
| 10 mM | 0.0925 mL | 0.4627 mL | 0.9253 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
