VIP236
VIP236 is a small-molecule drug conjugate targeting αvβ3 integrin. VIP236 achieves tumor homing via specific binding to αvβ3 integrin and delivers its payload to the tumor microenvironment. The linker of VIP236 is cleavable by neutrophil elastase, which is highly expressed in the tumor microenvironment, to release the payload 7-ethylcamptothecin. This payload induces DNA damage by inhibiting topoisomerase 1, thereby exerting anti-tumor effects. VIP236 exhibits excellent plasma stability and tumor targeting property, with a tumor/plasma payload ratio 10-fold higher than that of the single administration. It effectively induces tumor regression, reduces metastasis formation, and shows good tolerance in mouse models. VIP236 has been used in studies related to non-small cell lung cancer, clear cell renal cell carcinoma, colon cancer, triple-negative breast cancer, small cell lung cancer, and metastatic solid tumors.
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- CAS No.: 2418533-90-9
- Formule: C72H84N12Na2O20S
- Masse moléculaire:1515.55
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Stockage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Activité biologique
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Chemical Information
- Protocole
- Pureté et documentation
- Références
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Help & FAQs
Activité biologique
Description
In Vitro
VIP236 (5 mg/mL; 79 days stored at 4 °C) exhibits high hydrolytic stability when stored in pH 7.4 PBS buffer, with no observable degradation[1].
VIP236 (over 24 h incubated at 37 °C) is highly stable in rat plasma, with no observable degradation[1].
VIP236 (1 μM; 4 h incubated at 37 °C) is highly stable in mouse, rat, dog, and human hepatocytes, with ~80% of the parent compound remaining after incubation[1].
VIP236 (0-50 μM; up to 12 min) is efficiently cleaved by both human and mouse NE, with similar Km values between the two enzymes; cleavage follows Michaelis-Menten kinetics with Km values of 9.4 μM, 9.6 μM, 15.9 μM, 8.9 μM and kcat values of 593 1/min, 691 1/min, 94 1/min, 80 1/min at the tested enzyme concentrations[1].
VIP236 (72 h continuous exposure) exhibits NE-dependent cytotoxicity in NCI-H292 and LoVo cancer cell lines, with IC50 values decreasing 117-fold and 33-fold, respectively, when 20 nM NE is present during exposure[1].
VIP236 (1×10-5-1×10-13 M; 72 h) exhibits NE-dependent antiproliferative activity in 786-O, HT29, LoVo, SW480, NCI-H292, NCI-H69, and 4T1 cells, with single-digit nanomolar IC50 values in most cell lines in the presence of 10 nM NE and weak activity in the absence of NE[2].
VIP236 (1×10-13-1×10-5 M; 72 h) exhibits weak antiproliferative activity in 786-O, HT29, LoVo, SW480, NCI-H292, NCI-H69, and 4T1 cells without NE, but shows potent, VIP126-matched activity with single-digit nanomolar IC50 values (except for 4T1 cells) when co-incubated with 10 nM NE[3].
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:786-O human renal cell carcinoma, HT29 human colorectal cancer, LoVo human colorectal cancer, SW480 human colorectal cancer, NCI-H292 human pulmonary mucoepidermoid carcinoma, NCI-H69 human small cell lung cancer, 4T1 mouse mammary carcinoma cells
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Concentration:1 × 10-5-1 × 10-13 M (without NE); 1 × 10-5-1 × 10-13 M + 10 nM NE (with NE)
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Incubation Time:72 h
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Result:Showed weak antiproliferative activity with IC50 values in the two to three-digit nanomolar range (188 nM for 786-O, 245 nM for HT29, 91 nM for LoVo, 41 nM for SW480, 209 nM for NCI-H292, 486 nM for NCI-H69, >1000 nM for 4T1) in the absence of NE.
Increased cytotoxic activity to levels comparable to VIP126 alone, with single-digit nanomolar IC50 values (1.1 nM for 786-O, 8.7 nM for HT29, 2.9 nM for LoVo, 1.2 nM for SW480, 1.8 nM for NCI-H292, 3.0 nM for NCI-H69, 59 nM for 4T1) in the presence of 10 nM NE.
In Vivo
VIP236 (40-60 mg/kg; i.v.; 2 days on/5 days off for 4 weeks, once weekly for 4 weeks) inhibits orthotopic tumor growth and reduces micrometastases in the MA15191 metastatic TNBC PDX model, with the 40 mg/kg 2 days on/5 days off regimen achieving a 17% T/C ratio[1].
VIP236 (36 mg/kg; i.v.; 3 days on/4 days off) induces marked antitumor efficacy in 786-O RCC xenografts, with a T/C ratio of 0.19 and no evidence of significant toxicity[2].
VIP236 (40 mg/kg; i.v.; 3 days on/4 days off) induces marked antitumor efficacy in NCI-H69 SCLC xenografts, with a T/C ratio of 0.06 and 100% partial responses, and is more efficacious than cisplatin and topotecan while maintaining good tolerability[2].
VIP236 (36 mg/kg; i.v.; 3 days on/4 days off) induces significant renal cell carcinoma growth inhibition in mice, with a T/C ratio of 0.19 and partial or stable disease responses in all treated animals[3].
VIP236 (40 mg/kg; i.v.; 3 days on/4 days off) induces marked small cell lung cancer growth inhibition in all treated mice, with a T/C ratio of 0.06 and superior efficacy to cisplatin and topotecan[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:NMRI nu/nu (female)[1]
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Dosage:1 mg/kg; 3 mg/kg; 6 mg/kg; 20 mg/kg
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Administration:i.v.; day 1 (0 h pretreatment) and day 2 (24 h pretreatment)
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Result:Induced 68-79% γH2AX-positive cells at 24-48 h post 20 mg/kg treatment.
Returned γH2AX-positive cell levels to baseline 144 h after treatment.
Showed 36% γH2AX-positive cells in pretreatment tumor samples.
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Animal Model:NMRI nu/nu (female, 8-10 weeks old, 18-21 g, subcutaneous inoculation with 3×106 SW480 human CRC cells)[3]
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Dosage:23 mg/kg; 36 mg/kg; 40 mg/kg
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Administration:i.v.; 3 days on/4 days off
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Result:Achieved a treatment/control (T/C) ratio of 0.18 (23 mg/kg), 0.09 (36 mg/kg), and 0.10 (40 mg/kg), all with p < 0.001 compared to vehicle.
Induced partial responses (PRs) in 2/8 mice, stable disease (SD) in 4/8 mice, and progressive disease (PD) in 2/8 mice at 23 mg/kg.
Induced PRs in 7/8 mice and SD in 1/8 mouse at 36 mg/kg.
Induced PRs in 8/8 mice at 40 mg/kg.
Demonstrated significantly superior efficacy to 5-FU (p < 0.001) across all doses.
Caused moderate tumor regrowth after treatment cessation in all groups.
Essai clinique
| NCT Number | Sponsor | Condition | Start Date |
Phase
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|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
Chemical Information
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CAS No. 2418533-90-9
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Masse moléculaire 1515.55
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Formule C72H84N12Na2O20S
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SMILES
O=C(O[Na])C[C@@H](NC(NC1=CC=C(NC(NCCOCCOCCOCCC(N[C@H](C(N2[C@H](C(N[C@@H](C(C)C)C(O[C@@](C(OC3)=O)(CC)C4=C3C(N(CC5=C(CC)C(C=CC=C6)=C6N=C57)C7=C4)=O)=O)=O)CCC2)=O)CC(O[Na])=O)=O)=O)C=C1)=O)C8=CC=CC(NS(C9=CC=CC(NC(NCCC)=O)=C9)(=O)=O)=C8
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Please store the product under the recommended conditions in the Certificate of Analysis.
Protocole
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Phagocytosis Functional Assay
A phagocytosis functional assay measures the ability of phagocytic cells, such as neutrophils, macrophages, monocytes, or microglia/macrophages, to bind and internalize particulate targets including bacteria, yeast particles, beads, or myelin particles. Fluorescent flow-cytometry assays detect target uptake as fluorescence associated with gated phagocytes, while pH-sensitive dyes such as pHrodo increase signal in acidic phagosomal compartments and therefore preferentially report internalized particles rather than particles remaining outside the cell. Microscopy or high-content imaging can be used to confirm intracellular localization and, in some protocols, to follow uptake kinetics.
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Multiplex immunofluorescence IHC
Multiplex immunofluorescence IHC detects multiple protein biomarkers in one tissue section by sequential antibody staining, HRP-mediated tyramide fluorophore deposition, heat-mediated antibody stripping, nuclear counterstaining, multispectral imaging, spectral unmixing, and digital cell phenotyping; TSA deposits fluorophore near the antigen so the fluorescence signal remains after primary and secondary antibodies are removed, enabling repeated staining cycles, including with antibodies from the same host species. Classic FFPE tumor immune-profiling applications use panels such as CD3, CD8, CD68/CD163, FOXP3, PD-1, PD-L1, pancytokeratin, Ki67, and DAPI to identify tumor cells, immune-cell subsets, checkpoint-marker expression, co-expression phenotypes, cell density, and spatial relationships in the tumor microenvironment.
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Multiplex immunohistochemistry
Multiplex immunohistochemistry (mIHC), also known as tyramide dignal amplification (TSA), is an enzymatic detection method that uses horseradish peroxidase (HRP) to perform high-density in-situ labeling of target proteins or nucleic acids.
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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.
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Research Protocol for Cancer Immunology
Cancer immunology studies how the immune system recognizes, suppresses, edits, or fails to eliminate malignant cells through tumor antigen release, antigen presentation, T-cell priming, immune trafficking, tumor-cell killing, and feedback inhibition in the tumor microenvironment. The cancer-immunity cycle links tumor antigenicity, dendritic-cell priming, CD8+ T-cell infiltration, cytotoxic function, and immune-checkpoint regulation to tumor rejection or immune escape. Immune-checkpoint pathways such as PD-1/PD-L1 and CTLA-4 suppress antitumor T-cell activity and can be therapeutically blocked, but many tumors remain resistant because of poor antigen presentation, weak T-cell infiltration, suppressive myeloid cells, regulatory T cells, and tumor-intrinsic immune-exclusion programs. Unresolved questions include which immune-cell states predict response, how tumor-intrinsic pathways exclude immune cells, how myeloid suppression limits checkpoint blockade, and which combination strategies
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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.
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Orthotopic Cell-Line Xenograft
Orthotopic cell-line xenograft models involve implantation of human cancer cell lines into the anatomically corresponding organ of immunodeficient mice to reproduce tumor growth within a native microenvironment, enabling more clinically relevant tumor behavior compared with subcutaneous models. These models are widely used because orthotopic placement better recapitulates tumor progression, including invasion and metastatic spread, which are often underrepresented in heterotopic implantation systems. Compared with conventional xenografts, orthotopic implantation is described as more technically complex but provides improved simulation of tumor-microenvironment interactions and metastatic behavior, making it particularly valuable for translational oncology research. Surgical orthotopic implantation approaches have been emphasized as enabling faithful reproduction of clinical cancer features, including metastasis and disease progression patterns that align with the tumor’s organ of origi
Pureté et documentation
Références
[1]. Lerchen HG, et al. Discovery of VIP236, an αvβ3-Targeted Small-Molecule-Drug Conjugate with Neutrophil Elastase-Mediated Activation of 7-Ethyl Camptothecin Payload for Treatment of Solid Tumors. Cancers (Basel). 2023;15(17):4381. Published 2023 Sep 1. [Content Brief]
[2]. Lerchen HG, et al. A Small Molecule-Drug Conjugate (SMDC) Consisting of a Modified Camptothecin Payload Linked to an αVß3 Binder for the Treatment of Multiple Cancer Types. Cancers (Basel). 2022;14(2):391. Published 2022 Jan 13. [Content Brief]
[3]. Yang H, et al. Identification of an αvβ3-targeting bicyclic peptide with atypical norArg-Gly-Asp sequence. Commun Chem. 2026;9(1):83. Published 2026 Jan 12. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
VIP236 Related Classifications
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