CW-2
CW-2 is a CRBN-recruited PARP1 PROTAC degrader. CW-2 triggers multiple downstream biological effects including DNA damage accumulation, impaired DNA repair, mitochondrial-mediated apoptosis, intracellular ROS buildup and G1/S cell cycle arrest, as well as the regulation of oxidative phosphorylation, p53, PI3K-Akt and MAPK alongside ubiquitin proteolysis pathways. CW-2 enhances cell membrane permeability and intracellular platinum enrichment, exhibits detectable pharmacokinetic profiles after intraperitoneal administration in rats and drives differential gene expression. CW-2 can be applied to research on triple-negative breast cancer, non-small cell lung cancer, cisplatin-resistant non-small cell lung cancer, colon cancer and pancreatic cancer.
(Pink: PARP-1 ligand (HY-173441); Blue: Cereblon ligand (HY-173439); Black: linker (HY-173440)).
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- Fòrmula: C43H42Cl2FN11O10Pt
- Peso molecular:1157.85
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Almacenamiento:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Actividad biológica
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Chemical Information
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Help & FAQs
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Actividad biológica
CW-2 (1.0-100 μM; 12-72 h) is stable in non-reductive solutions for 72 h, undergoes reductive decomposition within 12 h in the presence of ascorbic acid, and has an optimized octanol-water partition coefficient of 2.11 that supports enhanced membrane permeability[1].
CW-2 (60 μM; 4 h) exhibits enhanced cellular uptake in MDA-MB-231 cells, delivering a total intracellular PROTAC-2 concentration of 34.1 μM, which is higher than direct PROTAC-2 treatment[1].
CW-2 (24-72 h) exhibits stability in DMSO, PBS, and 10% FBS culture medium over 72 h, and undergoes time-dependent reduction when incubated with 3.0 equivalents of ascorbic acid over 12 h[1].
CW-2 (0.3-80.0 μM; 48 h) potently inhibits the proliferation of multiple cancer cell lines, including Cisplatin (HY-17394)-resistant A549/CDDP cells, with an IC50 of 0.72 μM against MDA-MB-231 cells[1].
CW-2 (0.5-2 μM; 24-48 h) concentration-dependently degrades PARP1 protein in MDA-MB-231 cells, with near-complete suppression at 2 μM, via the ubiquitin-proteasome pathway[1].
CW-2 (1 μM; 48 h) induces higher levels of DNA damage in MDA-MB-231 cells than Cisplatin, Olaparib (HY-10162), or PROTAC-2, as indicated by elevated γ-H2AX expression[1].
CW-2 (1 μM; 48 h) regulates apoptosis-related proteins in MDA-MB-231 cells, upregulating pro-apoptotic BAX, caspase-3, and cleaved caspase-3, and downregulating anti-apoptotic Bcl-2 to promote apoptosis[1].
CW-2 (1 μM; 48 h) reduces mitochondrial membrane potential in MDA-MB-231 cells, indicating compromised mitochondrial integrity[1].
CW-2 (1 μM; 48 h) induces significantly higher intracellular ROS accumulation in MDA-MB-231 cells than control, Cisplatin, Olaparib, or PROTAC-2, with an MFI 3.4×100 that of the control[1].
CW-2 (1 μM; 48 h) induces apoptosis in MDA-MB-231 cells, with 12.6% early apoptosis and 5.3% late apoptosis after 48 h of treatment at 1 μM[1].
CW-2 (1 μM; 48 h) induces cell cycle arrest in the G1 and S phases of MDA-MB-231 cells after 48 h of treatment at 1 μM[1].
CW-2 (1 μM; 24 h) alters the expression of 4495 genes in MDA-MB-231 cells, with significant enrichment in cancer-related pathways and cellular processes including DNA damage response[1].
CW-2 (1 μM；24 h) alters the transcription of 4495 genes in MDA-MB-231 cells, modulating pathways related to DNA damage, cell cycle, apoptosis, and oncogenic signaling[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:MDA-MB-231
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Concentration:0.5-2 μM (48 h incubation); 1 μM + 5 μM proteasome inhibitor MG132, 1 μM + 5 μNEDD8-activating enzyme inhibitor MLN4924 (24 h incubation)
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Incubation Time:24 h (cotreatment with inhibitors); 48 h (single-agent treatment)
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Result:Markedly reduced intracellular PARP1 protein levels in a concentration-dependent manner and PARP1 was nearly fully suppressed at 2 μM.
Degradation of PARP1 was significantly inhibited by cotreatment with proteasome inhibitor or NEDD8-activating enzyme inhibitor.
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Cell Line:MDA-MB-231
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Concentration:1 μM
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Incubation Time:48 h
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Result:Significantly upregulated γ-H2AX protein expression.
Significantly upregulated the expression of pro-apoptotic proteins BAX, caspase-3, and cleaved caspase-3, while downregulating the anti-apoptotic protein Bcl-2, leading to a high BAX/Bcl-2 ratio.
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Cell Line:MDA-MB-231
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Concentration:1 μM
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Incubation Time:48 h
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Result:Increased early apoptosis to 12.6% and late apoptosis to 5.3%.
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Cell Line:MDA-MB-231
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Concentration:1 μM
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Incubation Time:48 h
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Result:Caused cell cycle arrest primarily in the G1 (60.6%) and S (23.4%) phases, with a reduction in the G2/M phase (8.4%).
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, five weeks old, subcutaneously injected with 5.0 × 106 MDA-MB-231 cells)[1]
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Dosage:17.8 mg/kg; 23.7 mg/kg
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Administration:i.p.; once every 3 days; 21 days
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Result:Achieved a tumor growth inhibition (TGI) rate of 79.6%, with almost no body weight loss observed compared to the PBS control.
Achieved a tumor growth inhibition (TGI) rate of 86.9%.
Induced marked disruption of tumor cell distribution and notable loss of cytoplasm in tumor cells.
Caused no significant damage to major organs (heart, liver, spleen, lungs, kidneys) at 17.8 mg/kg, while varying degrees of tissue damage in the heart, liver, and kidneys were observed at 23.7 mg/kg.
Induced substantial degradation of PARP1 protein and marked upregulation of γ-H2AX protein in tumor tissues, with concentration-dependent effects.
Chemical Information
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Peso molecular 1157.85
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Fòrmula C43H42Cl2FN11O10Pt
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SMILES
O=C1NN=C(C2=CC=CC=C21)CC3=CC(F)=C(C=C3)C(NCC(NC(CC4=CC=C(C=C4)OCC5=CN(N=N5)C6=C(C7=CC=C6)CN(C7=O)C8CCC(NC8=O)=O)C(O[Pt]([NH3])(Cl)(Cl)(O)[NH3])=O)=O)=O
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureza y Documentación
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Ficha de datos (278 KB)
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SDS (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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Instrucciones de manejo (2659 KB)
Referencias
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
CW-2 Related Classifications
HY-173437 Related Classifications
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