P5(PEG24)-VC-PAB-Exatecan
Based on 1 Customer Validation
P5 (PEG24)-VC-PAB-Exatecan is a TOP1 inhibitor payload with antibody-conjugation-dependent activity. Conjugation of P5 (PEG24)-VC-PAB-Exatecan with Trastuzumab (HY-P9907) generates a DAR8 antibody-drug conjugate (ADCs) with antibody-like pharmacokinetic properties. P5 (PEG24)-VC-PAB-Exatecan induces S-phase and G2-M-phase cell cycle arrest, DNA damage and apoptosis in target-positive tumor cells, and releases damage-associated molecular patterns (DAMP) related to immunogenic cell death (ICD). The ADCs prepared from it exert bystander killing effects on non-target tumor cells. ADCs based on P5 (PEG24)-VC-PAB-Exatecan exhibit linker stability in vitro and in vivo, show in vivo efficacy, and can be used in research related to HER2-positive cancers.
For research use only. We do not sell to patients.
- Purity: 98.59%
- CAS No.: 2928571-43-9
- Formula: C100H151FN9O36P
- Molecular Weight:2105.28
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Storage:
-20°C, stored under nitrogen
* In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen)
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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Biological Activity
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Chemical Information
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Solvent & Solubility
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
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Top1 |
Under optimized conditions, P5 (PEG24)-VC-PAB-Exatecan (LP5) (16 h; 25°C) is conjugated with Trastuzumab (HY-P9907) to produce a DAR8 ADC with a monomer yield of up to 99% and minimal aggregates[1].
P5 (PEG24)-VC-PAB-Exatecan (0.05-3 mg/mL; 7 d) potently inhibits the viability of HER2-positive SKBR-3 cells (EC50=12.5 ng/mL, maximum cell death rate 96%) and HCC-78 cells (EC50=97.6 ng/mL, maximum cell death rate 88%), but shows no activity against HER2-negative MDA-MB-468 cells[1].
Trastuzumab-LP5 DAR8 (0.05-3 mg/mL; 5 d) potently induces bystander killing of HER2-negative MDA-MB-468 cells during co-culture with HER2-positive SKBR-3 cells, and exhibits superior activity to Enhertu[1].
DAR8 ADC (0.5 mg/mL; 72 h) induces robust DNA damage in HER2-positive SKBR-3 cells, as evidenced by increased levels of phosphorylated H2AX, activated caspase 3, and cleaved PARP following treatment at 0.5 mg/mL for 72 h[1].
DAR8 ADC (3 mg/mL; 48 h) induces immunogenic cell death in HER2-positive SKBR-3 cells, which is characterized by increased cell surface calreticulin expression, ATP release, and HMGB1 release after treatment at 3 mg/mL for 48 h[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:HER2-positive SKBR-3 cells, HER2-positive HCC-78 cells, HER2-negative MDA-MB-468 cells
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Concentration:0.05-3 mg/mL DAR8 ADC
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Incubation Time:7 days
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Result:Inhibited SKBR-3 cell viability with an EC50 of 12.5 ng/mL and achieved a maximum of 96% dead cells.
Inhibited HCC-78 cell viability with an EC50 of 97.6 ng/mL and achieved a maximum of 88% dead cells.
Showed no cytotoxic effect on HER2-negative MDA-MB-468 cells.
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Cell Line:HER2-positive SKBR-3 cells, HER2-negative MDA-MB-468 cells (co-cultured; MDA-MB-468 cultured alone)
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Concentration:0.05-3 mg/mL DAR8 ADC
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Incubation Time:5 days
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Result:Induced bystander killing of HER2-negative MDA-MB-468 cells in co-culture with HER2-positive SKBR-3 cells, showing a tendency toward lower IC50 values and higher maximum cell killing compared with Enhertu.
Showed no effect on MDA-MB-468 cells cultured alone.
When conjugated with IgG1 to form a DAR8 antibody-drug conjugate (ADC), P5 (PEG24)-VC-PAB-Exatecan (10 mg/kg; intravenous injection; single administration) exhibits antibody-like in vivo pharmacokinetic stability, and fully maintains a drug-to-antibody ratio of 8 during 21 days of circulation in rats[1].
P5 (PEG24)-VC-PAB-Exatecan (20 mg/kg; intravenous injection; single administration), as the conjugated payload in Trastuzumab-LP5 DAR8, exhibits complete in vivo stability in mice, with the DAR maintained at the level of 8 throughout the 7-day circulation period[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:CB17-Scid (female, subcutaneous xenograft of NCI-N87 HER2-positive cells)[1]
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Dosage:0.25 mg/kg; 0.5 mg/kg; 1 mg/kg; 2 mg/kg
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Administration:i.v.; single dose
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Result:Achieved complete tumor regression in 10/10 mice at 2 mg/kg.
Achieved complete tumor regression in 8/10 mice at 1 mg/kg.
Achieved complete tumor regression in 8/10 mice at 0.5 mg/kg.
Achieved complete tumor regression in 0/10 mice at 0.25 mg/kg.
Demonstrated superior tumor growth inhibition over all tested dose levels compared to Enhertu, including greater efficacy at 0.5 mg/kg than Enhertu at 1 mg/kg.
Chemical Information
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CAS No. 2928571-43-9
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Appearance Oil
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Molecular Weight 2105.28
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Formula C100H151FN9O36P
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Color White to light yellow
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SMILES
O=C(N[C@@H](C(C)C)C(N[C@@H](CCCNC(N)=O)C(NC(C=C1)=CC=C1COC(N[C@H]2CCC3=C4C2=C5C(C(N6C5)=CC([C@](CC)(O)C(OC7)=O)=C7C6=O)=NC4=CC(F)=C3C)=O)=O)=O)C8=CC=C(NP(C#C)(OCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCO)=O)C=C8
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
-20°C, stored under nitrogen
* In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen)
Solvent & Solubility
DMSO : 100 mg/mL (47.50 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 (stored under nitrogen). 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 (stored under nitrogen). 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)
Purity & Documentation
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Data Sheet (285 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 (stored under nitrogen). 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 |
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| DMSO | 1 mM | 0.4750 mL | 2.3750 mL | 4.7500 mL | 11.8749 mL |
| 5 mM | 0.0950 mL | 0.4750 mL | 0.9500 mL | 2.3750 mL | |
| 10 mM | 0.0475 mL | 0.2375 mL | 0.4750 mL | 1.1875 mL | |
| 15 mM | 0.0317 mL | 0.1583 mL | 0.3167 mL | 0.7917 mL | |
| 20 mM | 0.0237 mL | 0.1187 mL | 0.2375 mL | 0.5937 mL | |
| 25 mM | 0.0190 mL | 0.0950 mL | 0.1900 mL | 0.4750 mL | |
| 30 mM | 0.0158 mL | 0.0792 mL | 0.1583 mL | 0.3958 mL | |
| 40 mM | 0.0119 mL | 0.0594 mL | 0.1187 mL | 0.2969 mL |
P5(PEG24)-VC-PAB-Exatecan Related Classifications
HY-163099 Related Classifications
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