RE:RE:New Study of TLD1433 & TLD1633 by Dr. McFarland et al.Hi Coop - I had forgotten about TLD1633. Back n 2017 they told us it was 15% more effective against gbm than TLD1433 and had a higher safety profile.
Toronto, Ontario – September 12, 2017
Theralase Technologies Inc. (“Theralase®” or the “Company”) (TSXV: TLT) (OTCQX: TLTFF), a leading biotech company focused on the commercialization of medical lasers to eliminate pain and the development of Photo Dynamic Compounds (“PDCs”) to destroy cancer, announced today that it has demonstrated increased efficacy with its latest, patented, licensed, anti-cancer drug, TLD-1633, when compared to its lead anti-cancer drug, TLD-1433.
The latest PDC, known as TLD-1633, has recently been shown to be approximately 15% more effective than TLD-1433 in the destruction of a human Glioblastoma Multiforme (“GBM”) cell line (U87), a deadly form of brain cancer.
In preclinical research, TLD-1633 has also demonstrated a lower dark toxicity, supporting an even higher safety profile than TLD-1433.
Pavel Kaspler, Ph.D., a research scientist at Theralase stated that, “Research on Theralase’s latest licensed anti-cancer drug, TLD-1633, is showing even stronger data preclinically than Theralase’s top performing anti-cancer drug TLD-1433. I look forward to expanding my research to assess the performance of TLD-1633 in various cancer lines, with and without the use of transferrin, as a transport system.”
Sherri McFarland, Ph.D., Professor, Department of Chemistry and Biochemistry, The University of North Carolina at Greensboro stated that, “TLD-1633 is a natural progression of the research work completed by our research labs in the development of TLD-1433. TLD-1633 has shown even stronger safety and efficacy in our labs than TLD-1433, and I am delighted to work with Theralase to optimize and expand their licenced PDC program, as we embark on additional cancer indications.”
Arkady Mandel, MD, Ph.D., D.Sc., Chief Scientific Officer of Theralase stated that, “I am delighted that TLD-1633 has been added to our growing list of compounds, identified by Dr. McFarland’s research program, in conjunction with our own, as potent anti-cancer agents. TLD-1433 was originally chosen as the lead anti-cancer PDC in our fight against Non-Muscle Invasive Bladder Cancer (“NMIBC”), because of its strong characteristics, but it seems an even more potent PDC, TLD-1633, may be better suited to be utilized for other cancers of the body, such as GBM, especially when combined with transferrin. This is truly ground-breaking research that myself and the entire Theralase research team are delighted to be involved with.”
Roger Dumoulin-White, President and CEO of Theralase stated that, “Theralase continues to expand our preclinical research and development, both in bringing new PDCs on-line and investigating new clinical applications, that we hope to translate into new clinical programs, in the not too distant future, via Phase Ib clinical studies.”
Theralase Demonstrates Increased Efficacy for Latest Anti-Cancer Drug jicoop wrote: FINALLY! Some luv for TLD 1633 , still in the picture, now wondering whatever happened to the other compound they had in their arsenal that was even a billion times more powerful than these two, I will try to look back on the older news releases and find the exact wording.
Coop
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Eoganacht wrote: McFarland Labs and the Leibniz Insitute of Photonic Technology in Germany collaborated on this study to determine the mechanism behind the photoinduced cytotoxicity of TLD1433 and its derivative TLD1633. Only the abstract is available for free. The full text of this one costs US $40.
Interaction with a Biomolecule Facilitates the Formation of the Function-Determining Long-Lived Triplet State in a Ruthenium Complex for Photodynamic Therapy Avinash Chettri, Houston D. Cole, John A. Roque III, Kilian R. A. Schneider, Tingxiang Yang, Colin G. Cameron, Sherri A. McFarland, and Benjamin Dietzek-Ivani Publication Date: February 18, 2022 Abstract
TLD1433 is the first ruthenium (Ru)-based photodynamic therapy (PDT) agent to advance to clinical trials and is currently in a phase II study for treating nonmuscle bladder cancer with PDT. Herein, we present a photophysical study of TLD1433 and its derivative TLD1633 using complex, biologically relevant solvents to elucidate the excited-state properties that are key for biological activity. The complexes incorporate an imidazo [4,5-f][1,10]phenanthroline (IP) ligand appended to α-ter- or quaterthiophene, respectively, where TLD1433 = [Ru(4,4′-dmb)2(IP-3T)]Cl2 and TLD1633 = [Ru(4,4′-dmb)2(IP-4T)]Cl2 (4,4′-dmb = 4,4′-dimethyl-2,2′-bipyridine; 3T = α-terthiophene; 4T = α-quaterthiophene). Time-resolved transient absorption experiments demonstrate that the excited-state dynamics of the complexes change upon interaction with biological macromolecules (e.g., DNA). In this case, the accessibility of the lowest-energy triplet intraligand charge-transfer (3ILCT) state (T1) is increased at the expense of a higher-lying 3ILCT state. We attribute this behavior to the increased rigidity of the ligand framework upon binding to DNA, which prolongs the lifetime of the T1 state. This lowest-lying state is primarily responsible for O2 sensitization and hence photoinduced cytotoxicity. Therefore, to gain a realistic picture of the excited-state kinetics that underlie the photoinduced function of the complexes, it is necessary to interrogate their photophysical dynamics in the presence of biological targets once they are known.