PMV6-PEG4-BI2536
Based on 1 Customer Validation
PMV6-PEG4-BI2536 is an RIPTAC-like bifunctional molecule that promotes the formation of the p53Y220C-PLK1 ternary complex (EC50 = 1.4 μM). PMV6-PEG4-BI2536 causes PLK1 mislocalization and inhibits PLK1 activity, inducing G2/M phase arrest and apoptosis in p53Y220C-mutant cells, while sparing cells with wild-type TP53. PMV6-PEG4-BI2536 can be used in research on uterine, gastric, pancreatic, prostate, and breast cancers harboring the p53Y220C mutation. PMV6-PEG4-BI2536 is composed of PMV6 (a p53Y220C mutant-binding ligand), PEG4 (a linker), and BI2536 (HY-159493) (a PLK inhibitor).
For research use only. We do not sell to patients.
- Purity : 98.47%
- Formula: C59H75F3N10O11S
- Molecular Weight:1189.35
-
Storage:Powder -20°C, 3 years ; In solvent -80°C, 6 months , -20°C, 1 month
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
-
Biological Activity
-
Chemical Information
-
Solvent & Solubility
- Protocols
- Purity & Documentation
- References
-
Help & FAQs
All Caspase Isoforms
More
Biological Activity
Description
IC50 & Target
[1]|
PLK1 |
Caspase 3 |
Caspase-7 |
Cellular Effect
|
Cell Line
|
Type | Value | Description | References |
|---|---|---|---|---|
| NUGC-3 | IC50 |
1713.0956 nM
|
Significantly inhibits cell proliferation.
Significantly inhibits cell proliferation.
|
41184486 |
| MFE-296 | IC50 |
4320.9284 nM
|
Significantly inhibits cell proliferation.
Significantly inhibits cell proliferation.
|
41184486 |
| BXPC-3 | IC50 |
8251.9582 nM
|
Significantly inhibits cell proliferation.
Significantly inhibits cell proliferation.
|
41184486 |
| MCF7 | IC50 |
1268.3102 nM
|
Significantly inhibits cell proliferation.
Significantly inhibits cell proliferation.
|
41184486 |
| Huh-7 | IC50 |
200000 nM
|
Does not significantly inhibit cell proliferation.
Does not significantly inhibit cell proliferation.
|
41184486 |
| LNCaP | IC50 |
14113.1353 nM
|
Does not significantly inhibit cell proliferation.
Does not significantly inhibit cell proliferation.
|
41184486 |
| DU-145 | IC50 |
20000 nM
|
Does not significantly inhibit cell proliferation.
Does not significantly inhibit cell proliferation.
|
41184486 |
| HepG2 | IC50 |
20000 nM
|
Does not significantly inhibit cell proliferation.
Does not significantly inhibit cell proliferation.
|
41184486 |
In Vitro
PMV6-PEG4-BI2536 (compound p53-01) (1 nM-10 μM; 24 h) induces an increase in luminescence signals in 293T cells co-transfected with NLS-LgBiT-p53-Y220C and mEGFP-PLK1-SmBiT, indicating the promotion of ternary complex formation between p53-Y220C and PLK1 (EC50 = 1.4 μM)[1].
PMV6-PEG4-BI2536 (62.5 nM-2 μM; 8 days) selectively inhibits the proliferation of mutant cells in a co-culture system of TP53Y220C-mutant 293T cells and wild-type 293T cells (EC50 = 443 nM)[1].
PMV6-PEG4-BI2536 (1 nM-1 μM; 8 days) dose not affect the proliferative capacity of P53-R273H (FL)-mutant 293T cells[1].
PMV6-PEG4-BI2536 (7.5 μM-1.5 μM; 5 days) significantly inhibits the proliferation of TP53Y220C-mutant 293T cells [1].
PMV6-PEG4-BI2536 (62.5 nM-1 μM; 7 days) dose not affect the proliferative capacity of P53-R273H (FL)-mutant CALU-1 cells or wild-type CALU-1 cells [1].
PMV6-PEG4-BI2536 (1.5 μM; 1 day) upregulates Caspase 3/7 activity and induces apoptosis in TP53Y220C-mutant 293T cells[1].
PMV6-PEG4-BI2536 (0.75-1.5 μM; 1 day) increases the proportion of early and late apoptotic cells in TP53Y220C-mutant 293T cells[1].
PMV6-PEG4-BI2536 (0.375-1.5 μM; 1 day) induces G2/M phase arrest in TP53Y220C-mutant 293T cells synchronized with Palbociclib (HY-50767)[1].
PMV6-PEG4-BI2536 (1.5 μM; 8.5 h) inhibits PLK1 activity in TP53Y220C-mutant 293T cells synchronized via double-thymidine block[1].
PMV6-PEG4-BI2536 (4 days) significantly inhibits the proliferation of most Y220C+ cell lines (MFE319 (IC50 = 1268.3102 nM), NUGC3 (IC50 = 1713.0956 nM), MFE296 (IC50 = 4320.9284 nM), BxPC-3 (IC50 = 8251.9582 nM)) and the Y220C- cell line MCF7 (IC50 = 1268.3102 nM). PMV6-PEG4-BI2536 has no significant effect on the proliferation of the Y220C+ cell line Huh7 (IC50 = 20000 nM) or most Y220C- cell lines (LNCaP (IC50 = 14113.1353 nM), DU145 (IC50 = 20000 nM), HepG2 (IC50 = 20000 nM)).[1].
PMV6-PEG4-BI2536 (0.16-1.25 μM; 9 days) shows no significant cytotoxic effect on TP53-knockout MFE319 cells in a co-culture system with wild-type MFE319 cells[1].
PMV6-PEG4-BI2536 (62.5-250 nM; 3 weeks) reduces the proportion of TP53Y220C-mutated 293T cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
-
Cell Line:TP53Y220C-mutant 293T cells
-
Concentration:0.75 μM, 1.5 μM
-
Incubation Time:1 day
-
Result:Specifically increased the proportion of early and apoptotic cells in p53-Y220C-expressing cells.
-
Cell Line:TP53Y220C-mutant 293T cells and parental 293T cells (synchronized by palbociclib (HY-50767))
-
Concentration:0.375 μM, 0.75 μM, 1.5 μM
-
Incubation Time:1 day
-
Result:Induced significant G2/M cell cycle arrest in p53-Y220C-expressing cells, and caused genome doubling (increased 8N DNA content) at higher doses.
-
Cell Line:TP53Y220C-mutant 293T cells and parental 293T cells (synchronized by double thymidine block)
-
Concentration:1.5 μM
-
Incubation Time:8.5 h
-
Result:Caused a massive accumulation of Cyclin B1 and decreased the level of phospho-PLK-binding motif in p53-Y220C-expressing cells, confirming the inhibition of PLK1 activity.
Chemical Information
-
Appearance Solid
-
Molecular Weight 1189.35
-
Formula C59H75F3N10O11S
-
Color Light yellow to light brown
-
SMILES
O=C(NCCOCCOCCOCCOCCC(N1CCC(NC2=CC=CC3=C2C=C(C#CCNC4=CC=C(S(=O)(C)=O)C=C4OC)N3CC(F)(F)F)CC1)=O)C5=CC=C(NC(N=C6N(C7CCCC7)[C@@H]8CC)=NC=C6N(C)C8=O)C(OC)=C5
-
Shipping
Room temperature in continental US; may vary elsewhere.
-
Storage
Powder -20°C 3 years In solvent -80°C 6 months -20°C 1 month
Solvent & Solubility
In Vitro:
DMSO : 100 mg/mL (84.08 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
In Vivo:
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 5 mg/mL (4.20 mM); Clear solution
This protocol yields a clear solution of ≥ 5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (50.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
-
-
-
-
Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
-
%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
-
%+
-
+%Tween-80 + +
-
%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Protocols
-
Apoptosis
Apoptosis, also called programmed cell death, is generally characterized by distinct morphological characteristics.
-
TUNEL staining for apoptotic DNA fragmentation
TUNEL staining detects DNA strand breaks by using terminal deoxynucleotidyl transferase to add labeled nucleotides to exposed 3′-OH DNA termini, generating either microscopic staining in fixed cells or tissue sections, or fluorescence/cytometric signal in cell suspensions. TUNEL positivity reflects DNA fragmentation but should not be interpreted alone as definitive apoptosis, because TUNEL can also label necrotic, autolytic, mechanically damaged, or DNA-repair-associated DNA breaks.
-
Flow cytometric DNA-content cell-cycle staining
Flow cytometric DNA-content cell-cycle staining measures the fluorescence intensity of DNA-bound fluorochromes in single cells or nuclei to estimate DNA content distributions, allowing assignment of populations to G0/G1, S, and G2/M phases by DNA histogram deconvolution. Propidium iodide (PI) intercalates into DNA, and PI fluorescence is proportional to cellular DNA content when staining is performed under conditions that make DNA accessible and minimize non-DNA signal. Cells with G2/M DNA content are expected to show approximately twice the fluorescence intensity of G0/G1 cells, while S-phase cells occupy intermediate fluorescence values. PI-based DNA-content analysis can also detect cells with fractional DNA content, often reported as sub-G1, when DNA fragmentation and extraction during staining reduce retained DNA signal in apoptotic cells. DAPI is an alternative DNA fluorochrome for univariate DNA-content analysis, while bivariate approaches combining DNA content with proliferation
-
Annexin V plus membrane-impermeant dye apoptosis staining
Annexin V-based apoptosis assays rely on the detection of phosphatidylserine (PS) externalization from the inner leaflet of the plasma membrane to the outer leaflet, an early biochemical hallmark of apoptosis. Fluorescently labeled Annexin V binds PS in a calcium-dependent manner, enabling identification of early apoptotic cells by flow cytometry or fluorescence microscopy. When combined with a membrane-impermeant DNA-binding dye (e. g. , propidium iodide), this approach allows discrimination between viable (Annexin V−/dye−), early apoptotic (Annexin V+/dye−), and late apoptotic or necrotic (Annexin V+/dye+) cell populations by assessing membrane integrity and PS exposure.
-
Apoptosis Solutions
Apoptosis is a regulated, generally non-lytic cell-death pathway that removes unwanted, damaged, infected, or abnormal cells through coordinated morphological changes, caspase activation, DNA fragmentation, and membrane remodeling. The intrinsic apoptosis pathway is controlled mainly by mitochondrial outer membrane permeabilization, BCL-2 family proteins, cytochrome c release, apoptosome formation, caspase-9 activation, and downstream executioner caspase-3/7 activation. The extrinsic apoptosis pathway is initiated by death receptors such as Fas, TNFR, and TRAIL receptors, which recruit adaptor proteins and activate caspase-8 before engaging executioner caspases or mitochondrial amplification through BID cleavage. Apoptosis is linked to many phenotypes, including cancer cell killing, tissue homeostasis, immune regulation, neurodegeneration, infection response, and treatment-induced cytotoxicity; unresolved questions include how apoptosis interacts with necroptosis, pyroptosis, ferroptos
-
Protocol for Cell Cycle
Cell-cycle analysis by flow cytometry measures DNA content in single cells to estimate the fraction of cells in G0/G1, S, and G2/M phases. Propidium iodide intercalates into DNA, and after RNA removal with RNase, fluorescence intensity reflects cellular DNA content: 2N cells are assigned to G0/G1, cells between 2N and 4N to S phase, and 4N cells to G2/M. DNA-content analysis alone cannot reliably separate G0 from G1 or G2 from M. Ki-67 can distinguish quiescent G0 cells from cycling cells, EdU or BrdU incorporation marks active DNA synthesis in S phase, and phospho-histone H3 staining identifies mitotic cells within the 4N population.
-
Genotoxicity/Mutagenicity Study
The bacterial reverse mutation assay detects point mutations that restore amino-acid prototrophy in auxotrophic Salmonella typhimurium or Escherichia coli tester strains; after exposure to a test article, mutagenic activity is read out as an increased number of revertant colonies on minimal agar compared with the vehicle control. The assay uses tester strains with different mutation targets so that base-substitution and frameshift mutagens can be detected, and testing is performed with and without exogenous mammalian metabolic activation because some chemicals require biotransformation to become mutagenic.
Purity & Documentation
-
Data Sheet (275 KB)
-
SDS (252 KB)
- English - EN (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 KB)
-
Handling Instructions (2659 KB)
References
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 0.8408 mL | 4.2040 mL | 8.4080 mL | 21.0199 mL |
| 5 mM | 0.1682 mL | 0.8408 mL | 1.6816 mL | 4.2040 mL | |
| 10 mM | 0.0841 mL | 0.4204 mL | 0.8408 mL | 2.1020 mL | |
| 15 mM | 0.0561 mL | 0.2803 mL | 0.5605 mL | 1.4013 mL | |
| 20 mM | 0.0420 mL | 0.2102 mL | 0.4204 mL | 1.0510 mL | |
| 25 mM | 0.0336 mL | 0.1682 mL | 0.3363 mL | 0.8408 mL | |
| 30 mM | 0.0280 mL | 0.1401 mL | 0.2803 mL | 0.7007 mL | |
| 40 mM | 0.0210 mL | 0.1051 mL | 0.2102 mL | 0.5255 mL | |
| 50 mM | 0.0168 mL | 0.0841 mL | 0.1682 mL | 0.4204 mL | |
| 60 mM | 0.0140 mL | 0.0701 mL | 0.1401 mL | 0.3503 mL | |
| 80 mM | 0.0105 mL | 0.0525 mL | 0.1051 mL | 0.2627 mL |
PMV6-PEG4-BI2536 Related Classifications
HY-179560 Related Classifications
Powered by Bioz