ArticleMolecular cancer therapeutics2016
Acetazolamide Serves as Selective Delivery Vehicle for Dipeptide-Linked Drugs to Renal Cell Carcinoma.
Article in Molecular cancer therapeutics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 59 citations in OpenAlex.
- A Microdosing Study withJournal of nuclear medicine : official publication, Society of Nuclear Medicine · 2021Trial
- From DNA-Encoded Chemistry to Tumor-Targeted Small Molecule Therapeutics.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Drug repurposing as a promising therapeutic strategy against renal cell carcinoma.Cancer chemotherapy and pharmacology · 2026Review
- Engineering Kidney-Targeted Drug Delivery Systems: Principles, Materials, and Emerging Strategies.International journal of nanomedicine · 2026Review
- Targeted drug conjugates in cancer therapy: Challenges and opportunities.Pharmaceutical science advances · 2024Review
- Radiolabeled 15-mer peptide internalization is mediated by megalin (LRP2 receptor) in a CRISPR/Cas9-based LRP2 knockout human kidney cell model.EJNMMI radiopharmacy and chemistry · 2024Article
- Emerging non-antibody‒drug conjugates (non-ADCs) therapeutics of toxins for cancer treatment.Acta pharmaceutica Sinica. B · 2024Review
- A DNA-encoded chemical library based on chiral 4-amino-proline enables stereospecific isozyme-selective protein recognition.Nature chemistry · 2023Article
- Deep Learning Approach for the Discovery of Tumor-Targeting Small Organic Ligands from DNA-Encoded Chemical Libraries.ACS omega · 2023Article
- Development of New Targeted Nanotherapy Combined with Magneto-Fluorescent Nanoparticles against Colorectal Cancer.International journal of molecular sciences · 2023Article
- Article
- Carbonic anhydrase IX stratifies patient prognosis and identifies nodal status in animal models of nasopharyngeal carcinoma using a targeted imaging strategy.European journal of nuclear medicine and molecular imaging · 2022Article
- DNA-Encoded Chemical Libraries: A Comprehensive Review with Succesful Stories and Future Challenges.ACS pharmacology & translational science · 2021Review
- Immunotherapy with Immunocytokines and PD-1 Blockade Enhances the Anticancer Activity of Small Molecule-Drug Conjugates Targeting Carbonic Anhydrase IX.Molecular cancer therapeutics · 2021Article
- Linker Hydrophilicity Modulates the Anticancer Activity of RGD-Cryptophycin Conjugates.Chemistry (Weinheim an der Bergstrasse, Germany) · 2021Article
- Sortase-Mediated Site-Specific Modification of Interleukin-2 for the Generation of a Tumor-Targeting Acetazolamide-Cytokine Conjugate.ACS omega · 2020Article
- Experimental Carbonic Anhydrase Inhibitors for the Treatment of Hypoxic Tumors.Journal of experimental pharmacology · 2020Review
- Octreotide Conjugates for Tumor Targeting and Imaging.Pharmaceutics · 2019Article
- Neutrophil Elastase Promotes Linker Cleavage and Paclitaxel Release from an Integrin-Targeted Conjugate.Chemistry (Weinheim an der Bergstrasse, Germany) · 2019Article
- A Novel Fully-Human Potency-Matched Dual Cytokine-Antibody Fusion Protein Targets Carbonic Anhydrase IX in Renal Cell Carcinomas.Frontiers in oncology · 2019Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
In most cases, cytotoxic drugs do not preferentially accumulate at the tumor site, causing unwanted toxicities and preventing dose escalation to therapeutically active regimens. Here, we show that acetazolamide derivatives, which bind to carbonic anhydrase IX (CAIX) on the surface of kidney cancer cells, selectively deliver payloads at the site of disease, sparing normal organs. Biodistribution studies, performed in tumor-bearing mice with acetazolamide derivatives bearing a technetium-99m chelator complex or a red fluorophore as payload, revealed a preferential tumor accumulation of the compound at doses up to 560 nmol/kg. The percentage of injected dose per gram in the tumor was dose-dependent and revealed optimal tumor:organ ratios at 140 nmol/kg, with a tumor:blood ratio of 80:1 at 6 hours. Acetazolamide, coupled to potent cytotoxic drugs via a dipeptide linker, exhibited a potent antitumor activity in nude mice bearing SKRC-52 renal cell carcinomas, whereas drug derivatives devoid of the acetazolamide moiety did not exhibit any detectable anticancer activity at the same doses. The observation of tumor regression with a noninternalizing ligand and with different cytotoxic moieties (MMAE and PNU-159682) indicates a general mechanism of action, based on the selective accumulation of the product on tumor cells, followed by the extracellular proteolytic release of the cytotoxic payload at the neoplastic site and the subsequent drug internalization into tumor cells. Acetazolamide-based drug conjugates may represent a promising class of targeted agents for the treatment of metastatic kidney cancer, as the majority of human clear cell renal cell carcinomas are strongly positive for CAIX. Mol Cancer Ther; 15(12); 2926-35. ©2016 AACR.
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