The Cancer Targeting Dye-Carrier
Circumventing drug toxicity and drug resistance is key to effective anticancer therapy. Da Zen’s products and technologies deliver targeted anticancer drugs, such as simvastatin and cisplatin conjugated to a cancer targeting dye-carrier, exclusively to cancer cells, with the drugs confined to the cancer cells for much longer than current therapies (up to three to four weeks) and no evidence of toxicity to normal organs and tissues. DaZen’s research has also shown that its targeted drugs and technologies can overcome therapeutic resistance by cancer cells to a broad spectrum of therapies, including chemotherapy, hormonal therapy, and targeted therapies with tyrosine kinase inhibitors, Gefitnib, Icotinib, and Everolimus.
This successful broad-spectrum re-sensitization to therapeutic agents has prompted Da Zen to search for the molecular mechanisms of re-sensitization. Previous research at Da Zen’s laboratories has demonstrated that these targeted therapies may promote programmed cell death by altering mitochondrial and lysosomal functions. Further exploration of the mechanisms of re-sensitization for various classes of therapeutic cancer agents at Da Zen can help inform the development of new drug targeting technology. The need to test and develop targeted drug systems in rigorous clinical trials is urgent, and moving discoveries from the laboratory to the clinic can significantly improve survival and quality of life for the millions who suffer from cancer.
Detection and treatment of brain tumors or metastases
(see US, CN, and EU 10,307,489 patent)
Targeted therapies utilizing dye-drug conjugates can improve diagnosis, detection, and treatment for brain tumors and brain metastases. The bi-functional dye-drug conjugates are efficiently taken up and retained by the cancer cells, assisting in the imaging of localized and disseminated tumors and their metastases. DaZen’s drug conjugates are significantly less toxic to organisms than unconjugated gemcitabine and cisplatin, while still allowing the same therapeutic effectiveness to be achieved.
Small molecule ligand-drug conjugates for targeted cancer therapy
(see CN 102,099,059 patent)
Therapies with a synthesized chemical conjugate of a promising drug with a targeting ligand can recognize a unique biomarker on the surface of a cancer cell.
Methods to target cancer cells with cancer-specific carrier-dyes
(see US 2017-0314056; related patent application US 15/487,320)
The developed drug carriers are dyes with various important therapeutic applications, including imaging of tumors and their metastases. Depending on the choice of conjugated/complexed drug, these dyes can deliver therapeutic drugs or radioactive agents to cancer cells during treatment. Some of these conjugates can also detect small tumors or metastases, i.e., of 1mm3.
Imaging methods for detection of cancer cells with dye compounds
(see US 2017-0354747; related patent application US 15/422,948)
These imaging methods utilize various cancer-targeting dyes, in particular those with alkyl sulfonic acid, alkyl carboxylic acid, or ester "tail" structures, e.g., MHI-148, MHI-25 (also known as IR783), MHI-160, and MHI-161.
Conjugate compounds with succinic ester linkers
(see US 2016-0310604; related patent application US 15/006,734)
Particular conjugates comprise a cancer-targeting dye linked to an anti-cancer drug via a succinic ester linker. These compounds find use in the delivery of the conjugated anti-cancer drug to cancer cells for treatment of cancer.
Sensitizing cancer cells to Tyrosine Kinase Inhibitors (TKIs)
(see WO2018075993; related national stage entries include US 16/343,645, further countries: EU, CN)
Sensitization of TKI-resistant cancer cells is achieved by utilizing dye-based amide/ester compounds conjugated to statins, platin-based drugs, or artemisinin. TKIs are important chemotherapeutics but, unfortunately, are prone to develop resistance. DaZen’s conjugates successfully treat tumors after resistance is developed or avoid its development, and can be co-administered with TKIs.
Sensitizing cancer cells to Cisplatin and other resistance-prone therapeutics
(see WO2018075994; related national stage entries include 16/343,697, further countries: EU, CN)
Dye-based amide/ester conjugates sensitize cancer cells to cisplatin and other resistance-prone therapeutics. The conjugates overcome resistance once formed or avoid its development, and can be co-administered with resistance-prone therapeutics.
Re-sensitizing tumors to hormonal antagonists and chemotherapy
(see WO2018075996; related national stage entries include US 16/343,732 further countries: EU, CN)
Resistance can be overcome and/or cancer cells can be re-sensitized, e.g., to hormonal antagonists and chemotherapy, utilizing dye-based amide/ester conjugates.
Tumor homing statin derivatives
(US 62/873,277 unpublished; Applied in CN as well)
Statins linked to dyes in an ester or amide bond result in improved targeting of cancer cells and reduced side effects. The conjugated compound in amide is slowly released, suggesting that a conjugated drug has full potential to exert biological activity without being hydrolyzed.
Tumor homing artemisinin derivatives
(US 62/873,293 unpublished; Applied in CN as well)
Artemisinin/dihydroartemisinin (DHA) derivatives linked to dyes are used to improve cancer therapy. These derivatives include conjugates wherein a linker is linked to one or, preferably, two DHA residue(s) via a particular set of bonds to improve growth inhibition of cancer cells.
Tumor-homing imaging agent
Heptamethine carbocyanine dye-cross-bridged tetraamine cyclam (ctc) chelator conjugates, their stable complexes with copper-64, and uses thereof for cancer imaging.
Tumor-homing targeting agent
Heptamethine carbocyanine dye-DOTA conjugates complexed with lutetium-177, yttrium-90, or gallium-68, and their uses for image-guided radiotherapy.