PROTAC PARP2 degrader-1
Based on 1 Customer Validation
PROTAC PARP2 degrader-1 is an orally active PARP2 PROTAC degrader with a DC50 of 2 μM. PROTAC PARP2 degrader-1 potently inhibits the enzymatic activities of PARP1 (IC50 = 2.74 nM) and PARP2 (IC50 = 0.32 nM), with approximately 10-fold higher selectivity for PARP2. PROTAC PARP2 degrader-1 induces cell cycle arrest and apoptosis, and exhibits significant anti-tumor efficacy in mouse models. PROTAC PARP2 degrader-1 can be used for the research of triple-negative breast cancer.
(Pink: PARP-2 ligand (HY-75706); Blue: Cereblon ligand (HY-131385); Black: linker (HY-W089232)).
연구목적의 판매만을 진행합니다. 환자를 대상으로 한 판매는 하지 않습니다.
- Purity : 98.29%
- CAS No.: 2925182-32-5
- 화학식: C43H50ClFN6O6
- 분자량:801.35
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보관:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
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Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
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용액&용해도
- Protocol
- 순도&문서
- References
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Help & FAQs
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Biological Activity
제품 설명
IC50 & Target
[1]|
PARP-2 2 μM (DC50) |
Cereblon |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
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| CAPAN-1 | IC50 |
0.061 μM
Compound: C8
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Antiproliferative activity against human BRCA2 -/- CAPAN-1 cells assessed as reduction in cell viability incubated for 5 to 10 days by MTT assay
Antiproliferative activity against human BRCA2 -/- CAPAN-1 cells assessed as reduction in cell viability incubated for 5 to 10 days by MTT assay
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[PMID: 35430559] |
In Vitro
PROTAC PARP2 degrader-1 (Compound C8) (5-10 days) potently inhibits the proliferation of MDA-MB-436, Capan-1, MDA-MB-468 and MDA-MB-231 cells, with IC50 values of 0.026 μM, 0.061 μM, 0.69 μM and 0.53 μM, respectively. Moreover, its activity in non-BRCA-mutant TNBC cells is significantly higher than that of Olaparib[1].
PROTAC PARP2 degrader-1 (C8) (0.5 μM; 24 h) selectively degrades nuclear PARP2 in MDA-MB-231 cells without affecting the level of cytoplasmic PARP2[1].
PROTAC PARP2 degrader-1 (0.312-5 μM; 14 days) potently and dose-dependently inhibits colony formation of MDA-MB-231 cells[1].
PROTAC PARP2 degrader-1 (0.156-2.5 μM; 24-48 h) induces dose-dependent G2/M cell cycle arrest in MDA-MB-436 and MDA-MB-231 cells[1].
PROTAC PARP2 degrader-1 (C8) (0.312-5 μM; 48-72 h) induces dose-dependent apoptosis in MDA-MB-436 and MDA-MB-231 cells, and [the sentence is incomplete in the source text, maintained as is] compared with Olaparib[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
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Cell Line:MDA-MB-231 (wild-type) TNBC cells
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Concentration:0.5 μM
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Incubation Time:24 h
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Result:Resulted in nearly complete degradation of nuclear PARP2, while cytoplasmic PARP2 fluorescence remained unchanged.
Showed no effect on PARP2 levels in either compartment when compared to inactive analog C8-M.
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Cell Line:MDA-MB-231 (wild-type) TNBC cells
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Concentration:0.312, 0.625, 1.25, 2.5 and 5 μM
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Incubation Time:14 days
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Result:Reduced colony formation in a dose-dependent manner, with significant inhibition observed at concentrations as low as 0.312 μM.
Nearly completely abolished colony formation at 1.25 μM and higher concentrations.
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Cell Line:MDA-MB-436 (BRCA1-/-) breast cancer cells, MDA-MB-231 (wild-type) TNBC cells
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Concentration:0.156, 0.312, 0.625, 1.25, 2.52.5 μM
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Incubation Time:24 h (MDA-MB-231); 48 h (MDA-MB-436)
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Result:Induced a dose-dependent G2/M cell cycle arrest in both cell lines, with a significantly greater arrest compared to Olaparib at equivalent concentrations.
Increased G2/M phase distribution in MDA-MB-231 cells from ~26% in controls to ~37% at 1.25 μM C8.
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Cell Line:MDA-MB-436 (BRCA1-/-) breast cancer cells, MDA-MB-231 (wild-type) TNBC cells
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Concentration:0.312, 0.625, 1.25, 2.5 and 5 μM
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Incubation Time:48 h (MDA-MB-231); 72 h (MDA-MB-436)
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Result:Induced dose-dependent apoptosis in both cell lines, with a more pronounced effect in MDA-MB-231 cells.
Reached ~90% apoptosis in MDA-MB-231 cells at 5 μM C8, compared to ~48% with Olaparib.
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:BALB/c nude (female, 5-6 weeks old, subcutaneous xenograft model)[1]
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Dosage:100 mg/kg (ig); 12.5 mg/kg (ip); 25 mg/kg (ip)
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Administration:ig; ip; daily; 21 days
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Result:Achieved tumor growth inhibition (TGI) of 63.5% at 100 mg/kg ig.
Achieved tumor growth inhibition (TGI) of 82.9% at 12.5 mg/kg ip.
Achieved tumor growth inhibition (TGI) of 98.3% at 25 mg/kg ip.
Caused no obvious weight loss, morbidity, or mortality during 21-day treatment.
Showed no obvious histopathological lesions in heart, liver, spleen, kidney, and lung at 25 mg/kg ip.
Chemical Information
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CAS No. 2925182-32-5
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Appearance Solid
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분자량 801.35
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화학식 C43H50ClFN6O6
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Color White to off-white
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SMILES
O=C1NN=C(CC2=CC=C(C(C(N3CCN(CC3)C(CCCCCCCCCNC(COC4=CC=C5C(CCCN5C(CCl)=O)=C4)=O)=O)=O)=C2)F)C6=C1C=CC=C6
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선적
Room temperature in continental US; may vary elsewhere.
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보관
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
용액&용해도
In Vitro:
DMSO : 100 mg/mL (124.79 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: ≥ 2.5 mg/mL (3.12 mM); Suspended solution
This protocol yields a suspended solution of ≥ 2.5 mg/mL (saturation unknown). Suspended solution can be used for oral and intraperitoneal injection.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 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:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%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.
Protocol
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Apoptosis
Apoptosis, also called programmed cell death, is generally characterized by distinct morphological characteristics.
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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.
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Cell Cytotoxicity Assay
Cytotoxicity assays are usually based on the assessment of cell membrane damage, which can also be indirectly detected by measuring cell viability. Detection methods include MTT assay, CKK-8 assay, LDH assay and ATP assay, etc.
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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
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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.
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BrdU Incorporation Assay
Bromodeoxyuridine (BrdU) incorporation assay is based on the principle that BrdU, a thymidine analog, is incorporated into newly synthesized DNA during the S phase of the cell cycle, thereby serving as a marker of DNA replication and cellular proliferation. Incorporated BrdU can be detected using anti-BrdU antibodies following DNA denaturation, enabling visualization or quantification of proliferating cells through immunochemical detection methods such as immunofluorescence or immunohistochemistry.
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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
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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.
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Breast Cancer Modeling
Breast cancer is a heterogeneous cancer, and it has been distinguished into four subtypes: luminal A, luminal B, HER2-positive and basal-like. Molecular mutations, epigenetic alterations, hormone exposure and immune microenvironment are related to the progression of breast cancer.
순도&문서
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Data Sheet (274 KB)
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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)
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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 | 1.2479 mL | 6.2395 mL | 12.4789 mL | 31.1974 mL |
| 5 mM | 0.2496 mL | 1.2479 mL | 2.4958 mL | 6.2395 mL | |
| 10 mM | 0.1248 mL | 0.6239 mL | 1.2479 mL | 3.1197 mL | |
| 15 mM | 0.0832 mL | 0.4160 mL | 0.8319 mL | 2.0798 mL | |
| 20 mM | 0.0624 mL | 0.3120 mL | 0.6239 mL | 1.5599 mL | |
| 25 mM | 0.0499 mL | 0.2496 mL | 0.4992 mL | 1.2479 mL | |
| 30 mM | 0.0416 mL | 0.2080 mL | 0.4160 mL | 1.0399 mL | |
| 40 mM | 0.0312 mL | 0.1560 mL | 0.3120 mL | 0.7799 mL | |
| 50 mM | 0.0250 mL | 0.1248 mL | 0.2496 mL | 0.6239 mL | |
| 60 mM | 0.0208 mL | 0.1040 mL | 0.2080 mL | 0.5200 mL | |
| 80 mM | 0.0156 mL | 0.0780 mL | 0.1560 mL | 0.3900 mL | |
| 100 mM | 0.0125 mL | 0.0624 mL | 0.1248 mL | 0.3120 mL |
PROTAC PARP2 degrader-1 Related Classifications
HY-183013 Related Classifications
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