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Ref Type Journal Article
PMID (35053556)
Authors Lerchen HG, Stelte-Ludwig B, Kopitz C, Heroult M, Zubov D, Willuda J, Schlange T, Kahnert A, Wong H, Izumi R, Hamdy A
Title A Small Molecule-Drug Conjugate (SMDC) Consisting of a Modified Camptothecin Payload Linked to an αVß3 Binder for the Treatment of Multiple Cancer Types.
Journal Vol Issue Date Pages Journal Short Title
Cancers 14 2 2022 Jan 13 Cancers (Basel)
URL
Abstract Text To improve tumor selectivity of cytotoxic agents, we designed VIP236, a small molecule-drug conjugate consisting of an αVβ3 integrin binder linked to a modified camptothecin payload (VIP126), which is released by the enzyme neutrophil elastase (NE) in the tumor microenvironment (TME). The tumor targeting and pharmacokinetics of VIP236 were studied in tumor-bearing mice by in vivo near-infrared imaging and by analyzing tumor and plasma samples. The efficacy of VIP236 was investigated in a panel of cancer cell lines in vitro, and in MX-1, NCI-H69, and SW480 murine xenograft models. Imaging studies with the αVβ3 binder demonstrated efficient tumor targeting. Administration of VIP126 via VIP236 resulted in a 10-fold improvement in the tumor/plasma ratio of VIP126 compared with VIP126 administered alone. Unlike SN38, VIP126 is not a substrate of P-gp and BCRP drug transporters. VIP236 presented strong cytotoxic activity in the presence of NE. VIP236 treatment resulted in tumor regressions and very good tolerability in all in vivo models tested. VIP236 represents a novel approach for delivering a potent cytotoxic agent by utilizing αVβ3 as a targeting moiety and NE in the TME to release the VIP126 payload-designed for high permeability and low efflux-directly into the tumor stroma.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
VIP236 VIP236 0 1
Drug Name Trade Name Synonyms Drug Classes Drug Description
VIP236 VIP-236|VIP 236 VIP236 is a small molecule-drug conjugate comprising an alpha5beta3 integrin-targeted molecule linked to a modified camptothecin payload, which potentially induces cytotoxic effects against tumor cells and inhibition of tumor growth (PMID: 35053556).
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References