P5(PEG24)-VC-PAB-Exatecan

Name: P5(PEG24)-VC-PAB-Exatecan
Brand: MedChemExpress
SKU: HY-163099
Rating: 4.5 (0 reviews)

Cat. No.: HY-163099: Data Sheet
COA

SDS
Handling Instructions
FAQs
Technical Support

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.

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P5(PEG24)-VC-PAB-Exatecan 화학구조

CAS No. : 2928571-43-9

사이즈	재고	수량
1 mg	해외재고보유	Estimated Time of Arrival: December 31
5 mg	견적 받기	Estimated Time of Arrival: December 31
10 mg	해외재고보유	Estimated Time of Arrival: December 31
50 mg	견적 받기
100 mg	견적 받기

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고객리뷰

Based on 1 Customer Validation

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Topoisomerase Topo I Topo II DNA gyrase

Biological Activity
순도&문서
References
고객리뷰

제품 설명

IC₅₀ & Target

Top1

In Vitro

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.

Cell Cytotoxicity Assay^[1]

Cell Line:	HER2-positive SKBR-3 cells, HER2-positive HCC-78 cells, HER2-negative MDA-MB-468 cells
Concentration:	0.05-3 mg/mL DAR8 ADC
Incubation Time:	7 days
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.

Cell Cytotoxicity Assay^[1]

Cell Line:	HER2-positive SKBR-3 cells, HER2-negative MDA-MB-468 cells (co-cultured; MDA-MB-468 cultured alone)
Concentration:	0.05-3 mg/mL DAR8 ADC
Incubation Time:	5 days
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.

In Vivo

The conjugate of P5 (PEG24)-VC-PAB-Exatecan and Palivizumab (HY-P9944) (0.25-2 mg/kg; intravenous injection; single administration) exhibits excellent in vivo efficacy in a gastric cancer xenograft model. After a single intravenous administration, the complete response rate reaches 100% at the 2 mg/kg dose, 80% at the 1 mg/kg dose, and 80% at the 0.5 mg/kg dose^[1].
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.

Animal Model:	CB17-Scid (female, subcutaneous xenograft of NCI-N87 HER2-positive cells)^[1]
Dosage:	0.25 mg/kg; 0.5 mg/kg; 1 mg/kg; 2 mg/kg
Administration:	i.v.; single dose
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.

분자량

2105.28

화학식

C₁₀₀H₁₅₁FN₉O₃₆P

CAS No.

2928571-43-9

Appearance

Solid

Color

White to light yellow

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

선적

Room temperature in continental US; may vary elsewhere.

보관

4°C, stored under nitrogen

*In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen)

용액&용해도

In Vitro:

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)

Preparing
Stock Solutions

Concentration Solvent Mass	1 mg	5 mg	10 mg

1 mM	0.4750 mL	2.3750 mL	4.7500 mL
5 mM	0.0950 mL	0.4750 mL	0.9500 mL
10 mM	0.0475 mL	0.2375 mL	0.4750 mL

View the 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.

몰농도 계산기
농도 희석 계산기

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Concentration _(start) × Volume _(start) = Concentration _(final) × Volume _(final)

This equation is commonly abbreviated as: C₁V₁ = C₂V₂

Concentration _(start)

Volume _(start)

Concentration _(final)

Volume _(final)

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.

Calculation results:

Working solution concentration: mg/mL

순도&문서

Purity: 99.74%

Select Batch:

Data Sheet (285 KB) SDS (252 KB)

COA (263 KB) HNMR (327 KB) RP-HPLC (263 KB)

Handling Instructions (2659 KB)

References

[1]. Schmitt S, et al. Design and Evaluation of Phosphonamidate-Linked Exatecan Constructs for Highly Loaded, Stable, and Efficacious Antibody-Drug Conjugates. Mol Cancer Ther. 2024;23(2):199-211. [Content Brief]

Complete Stock Solution Preparation Table

Optional Solvent	Concentration Solvent Mass	1 mg	5 mg	10 mg	25 mg

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