- |||||||||| Ruvidar (TLD-1433) / Theralase, BOLD-100 / Bold Therap
Review, Journal: From Concept to Cure: The Road Ahead for Ruthenium-Based Anticancer Drugs. (Pubmed Central) - Oct 7, 2024
Among these, Ru complexes, exemplified by BOLD-100 and TLD1433, have shown exceptional promise due to their selective activity, lower propensity for resistance, and the ability to target spescific cellular pathways. This paper explores the journey of such Ru candidates, focusing on the mechanisms, efficacy, and clinical potential of these Ru-based drugs, which stand at the forefront of current research, aiming to provide more targeted, less toxic, and highly effective cancer treatments.
- |||||||||| Ruvidar (TLD-1433) / Theralase
Applications of photoactivated metallodrugs for cancer therapy (Virtual; Virtual Session (Virtual Only)) - Mar 12, 2024 - Abstract #ACSSp2024ACS_Sp_11156;
P2
Our own TLD1433, a Ru(II) polypyridyl complex incorporating an oligothienyl-containing ligand, is one example and is currently in Phase 2 clinical trials (NCT03945162) for treating non-muscle invasive bladder cancer (NMIBC) with PDT. Herein, we report a novel class of metal-based PSs that are structurally similar to TLD1433 and highlight their light-driven PDT effects.
- |||||||||| Ruvidar (TLD-1433) / Theralase
Effects of methyl and thiophene substitution on redox potentials and electrochemical properties of [ru(bpy[cc1])2(ip-nt)]2+ (Virtual; Virtual Session (Virtual Only)) - Mar 12, 2024 - Abstract #ACSSp2024ACS_Sp_9060;
One example of a successful PS is Ru-based TLD1433 from our lab, which is currently in Phase 2 clinical trials to treat bladder cancer with PDT...Thus, this study focuses on the effect of CH 3 substituents on bipyridyl coligands and number of thiophenes in the [Ru(bpy) 2 (IP- n T)] 2+ [Ru(dmb) 2 (IP- n T)] 2+ family, where bpy is 2,2?-bipyridine, dmb is 5,5?-di(methyl)-bpy, IP is imidazo[4,5- f ][1,10]phenanthroline, and n T is the number of thiophenes ( n =0 to 4). In this vein, cyclic differential pulse voltammetry (CDPV) was used to characterize the ground state redox potentials and other electrochemical properties of these metal complex photosensitizers .
- |||||||||| Ruvidar (TLD-1433) / Theralase
Journal: Using Biological Photophysics to Map the Excited-State Topology of Molecular Photosensitizers for Photodynamic Therapy. (Pubmed Central) - Apr 7, 2023
This contribution targets a general problem in phototherapy, which is how to interrogate the light-triggered, function-determining processes of the PSs in the relevant biological environment, and establishes methodological advances to study the ultrafast photoinduced processes in TLD1433 when taken up by MCF7 cells. We generalize the methodological developments and results in terms of molecular physics by applying them to TLD1433's analogue TLD1633, making this study a benchmark to investigate the excited-state dynamics of phototoxic compounds in complex biological environment.
- |||||||||| Photofrin (porfimer sodium) / Advanz Pharma, TLD-1433 / Theralase
Development of novel metal-based photosensitizers for photodynamic therapy (Virtual Session (Virtual Only)) - Feb 14, 2023 - Abstract #ACSSp2023ACS_SP_1413;
Ruthenium- and osmium-based PSs are particularly promising, with our own TLD1433 in Phase II clinical trials for the treatment of non-muscle invasive bladder cancer. This presentation will focus on the design, synthesis, and characterization of a series of next-generation metal-based PSs.
- |||||||||| Photofrin (porfimer sodium) / Advanz Pharma, TLD-1433 / Theralase
Metallodrug photosensitizers for light-based cancer therapy (Virtual Session (Virtual Only)) - Feb 14, 2023 - Abstract #ACSSp2023ACS_SP_1400;
P2
Our own TLD1433, a Ru(II) polypyridyl complex incorporating a key oligothienyl unit, in currently in Phase 2 clinical trials (NCT03945162) for treating non-muscle invasive bladder cancer (NMIBC) with PDT. In this work, we report the design and development of a new class of metallodrug PSs, which are structurally related to TLD1433, and investigate their photochemical and photobiological properties.
- |||||||||| TLD-1433 / Theralase
Rational design of metallodrug photosensitizers for photodynamic therapy (Virtual Session (Virtual Only)) - Feb 14, 2023 - Abstract #ACSSp2023ACS_SP_1059;
P2
Ruthenium and osmium polypyridyl PSs serve as examples, with our own TLD1433 currently being in phase II clinical trials for the treatment of non-muscle invasive bladder cancer (Clinicaltrials.gov identifier NCT03945162). This presentation will highlight the application of rational molecular design to metallodrug PS development for PDT.
- |||||||||| TLD-1433 / Theralase
Review, Journal, Combination therapy, Monotherapy: Ruthenium-based antitumor drugs and delivery systems from monotherapy to combination therapy. (Pubmed Central) - Nov 22, 2022
NAMI-A, KP1019, TLD1433 and other ruthenium complexes have entered clinical research...During the development of ruthenium complexes, drug delivery forms of ruthenium antitumor drugs have also evolved from single-molecule drugs to nanodrug delivery systems. The review summarizes the following aspects: (1) ruthenium complexes from monotherapy to combination therapy, including the development of single-molecule compounds, carrier nanomedicine, and self-assembly of carrier-free nanomedicine; (2) ruthenium complexes in the process of ADME in terms of absorption, distribution, metabolism and excretion; (3) the applications of ruthenium complexes in combination therapy, including photodynamic therapy (PDT), photothermal therapy (PTT), photoactivated chemotherapy (PACT), immunotherapy, and their combined application; (4) the future prospects of ruthenium-based antitumor drugs.
- |||||||||| TLD-1433 / Theralase
Light-triggered metallodrugs for phototherapy applications (W178b (McCormick Place Convention Center)) - Aug 9, 2022 - Abstract #ACSFall2022ACS_Fall_8209;
TLD1433, a metal complex designed in our laboratory, is an example that is also the first ruthenium-based photosensitizer for PDT to advance to clinical trials. This presentation will discuss some of our current research efforts that were shaped by the design and development of TLD1433 as a bladder cancer PDT agent.
- |||||||||| TLD-1433 / Theralase
Effects of triflouromethyl substitution and thiophene chain length on energy levels and electrochemical characteristics of [Ru(dtfmbpy)2(IP-nT)]2+ (W179a (McCormick Place Convention Center)) - Aug 9, 2022 - Abstract #ACSFall2022ACS_Fall_7005;
We have been particularly focused on Ru(II)- and Os(II)-oligothiophene complexes, with our Ru-based TLD1433 having advanced to Phase 2 clinical trials for treating bladder cancer with PDT...Together, the photophysical and electrochemical properties will inform which features and characteristics give rise to the potent PDT effect that we observe from such systems.This study focuses on the effect of CF3 substituents on bipyridyl coligands and thiophene chain length in the [Ru(dtfmbpy)2(IP-nT)]2+ family, where, dtfmbpy is 2,5′-di(triflouromethyl)-2,2′-bipyridine, IP is imidazo[4,5-f][1,10]phenanthroline, and nT is the number of thiophenes (n=0 to 4). In this vein, two complementary electrochemical techniques, cyclic voltammetry (CV) and cyclic differential pulse voltammetry (CDPV), were used in tandem to find the absolute energy levels and electrochemical properties of these metal complex photosensitizers.
- |||||||||| TLD-1433 / Theralase
Light-responsive metallodrugs for phototherapy (Virtual-only (Zoom)) - Aug 9, 2022 - Abstract #ACSFall2022ACS_Fall_4806;
TLD1433 and other Ru and Os-based PSs we have developed display possible modes of action that extend beyond ROS. Herein, we will discuss some of these possibilities that may contribute to their light-driven antitumor and antimicrobial effects.
- |||||||||| TLD-1433 / Theralase
Development of novel metal-based photosensitizers for photodynamic therapy (Virtual-only (Zoom)) - Aug 9, 2022 - Abstract #ACSFall2022ACS_Fall_3629;
Ruthenium- and osmium-centered PSs are particularly promising, with our own TLD1433 in phase 2 clinical trials for the treatment of non-muscle invasive bladder cancer. This presentation will focus on the design, synthesis, and characterization of a series of next-generation metal-based PSs.
- |||||||||| Photofrin (porfimer sodium) / Advanz Pharma, TLD-1433 / Theralase
Photoactive metallodrugs for applications in cancer therapy (Virtual-only (Zoom)) - Aug 9, 2022 - Abstract #ACSFall2022ACS_Fall_1627;
P2
Recently reported ruthenium- and osmium- centered PSs may serve as examples, with our own TLD1433 having entered a Phase 2 clinical trial (NCT03945162) for the treatment of non-muscle invasive bladder cancer. Herein, we report the rational design and development of a new class of metal-based PSs and their light-driven PDT effects.
- |||||||||| cisplatin / Generic mfg.
Review, Journal: Ruthenium(ii)-arene complexes as anti-metastatic agents, and related techniques. (Pubmed Central) - Mar 1, 2022
With the discovery of cisplatin, a vast area of applications of metallodrugs in cancer treatment was opened but due to the side effects caused by the cisplatin complexes, researchers began to look for alternatives with similar anticancer properties but fewer side effects...NAMI-A, KP1019, KP1339, and TLD1433, have entered clinical trials...Herein, we provide information and probable mechanistic pathways for ruthenium(ii)-arene complexes that have been studied, so far, for their anti-metastatic activities. Also, we discuss the techniques and their significance for determining the anti-metastatic effects of the complexes.
- |||||||||| Stakel (padeliporfin) / Steba Biotech, TLD-1433 / Theralase
Clinical, Journal: Clinical Development of Metal Complexes as Photosensitizers for Photodynamic Therapy of Cancer. (Pubmed Central) - Feb 11, 2022
In an effort to overcome these drawbacks, much attention has been devoted towards the incorporation of a metal ion. Herein, the clinical development of metal containing compounds including Purlytin ® , Lutrin ® /Antrin ® , Photosens ® , TOOKAD ® soluble or TLD-1433 is critically reviewed.
- |||||||||| TLD-1433 / Theralase
Metallodrug photosensitizers that exert anticancer effects in extreme hypoxia (Virtual Room (Marriott Marquis San Diego Marina)) - Jan 28, 2022 - Abstract #ACSSp2022ACS_Sp_10037;
These systems can be rationally tuned to alter their photophysical, photochemical, and biological properties. Here, we will discuss our strategies for achieving photocytotoxicity in hypoxia with light-triggered metallodrugs, with emphasis on the metal-ligand combinations and their possible modes of action.
- |||||||||| TLD-1433 / Theralase
Next-generation metallodrugs for light-triggered cancer therapy (Zoom Room 18 (Virtual Room)) - Jan 28, 2022 - Abstract #ACSSp2022ACS_Sp_9379;
One example is our own TLD1433, currently in a Phase II clinical trial for treating bladder cancer with PDT...In this presentation, we will discuss the design and development of metallodrug PSs that can potentially exploit both PDT and PCT effects that lead to the hallmarks of immunogenic cell death. The emphasis will be on the structural features and photophysical models that produce excited triplet states with characteristic reactivities.
- |||||||||| TLD-1433 / Theralase
Role of Methoxy Substituents Osmium Polypyridyl pi-Expansive Metal Complexes in Photodynamic Therapy (Zoom Room 12 (Virtual Room)) - Jan 28, 2022 - Abstract #ACSSp2022ACS_Sp_8126;
For example, TLD1433 is a ruthenium based polypyridyl pi-expansive oligothiophene metal complex developed by our lab that is in Phase II clinical trials for bladder cancer PDT...Their photobiological activities were tested in vitro against SKMEL-28 cancer cells. These activities were compared against those for analogous Os(II) polypyridyl complexes to establish structure-activity relationships.
- |||||||||| TLD-1433 / Theralase
Comparative Evaluation of a New Class of Metal-Centered Polypyridyl Photosensitizers (Zoom Room 12 (Virtual Room)) - Jan 28, 2022 - Abstract #ACSSp2022ACS_Sp_8125;
P2
Recently developed Ru- and Os-centered PSs serve as examples, with our own TLD1433 having entered Phase II clinical trials (ClinicalTrials.gov Identifier: NCT03945162) for the treatment of bladder cancer. This presentation will describe the rational molecular design of a new class of metal complexes that act via novel mechanism(s) and may change the scope of PDT.
- |||||||||| Photofrin (porfimer sodium) / Advanz Pharma, TLD-1433 / Theralase
Light-Triggered Metallodrugs and their Coligand Effects (Room 6E (San Diego Convention Center)) - Jan 28, 2022 - Abstract #ACSSp2022ACS_Sp_6057;
Ruthenium and Osmium centered PSs are particularly promising, with our own TLD1433 in Phase 2 clinical trials for the treatment of bladder cancer. This presentation will focus on the design, synthesis, and characterization of a series of metal-based PSs.
- |||||||||| TLD1433 / Theralase
Journal: Minimal required PDT light dosimetry for nonmuscle invasive bladder cancer. (Pubmed Central) - Sep 26, 2021
Herein, we will discuss some of these possibilities that may contribute to their light-driven antitumor effects. We demonstrate the need for adequate irradiance monitoring independent of a photosensitizer's specific uptake ratio.
- |||||||||| cisplatin / Generic mfg.
Journal: Chiral resolution and absolute configuration determination of new metal-based photodynamic therapy antitumor agents. (Pubmed Central) - Aug 26, 2021
The advent of cisplatin as a cancer drug in the late 1960s generated considerable interest in the use of transition metal complexes as cancer therapy agents...Recently a Ru(II) metal-organic dyad (TLD1433) has provided promising results as a photodynamic therapy (PDT) agent for some types of cancer...However, preparative LC provided sufficient amounts of these novel PDT agents to determine their absolute configurations by vibrational circular dichroism (VCD). The synthesis, separation and absolute configuration determinations are described and discussed in detail.
- |||||||||| Photofrin (porfimer sodium) / Advanz Pharma, TLD1433 / Theralase
[VIRTUAL] Design and development of novel metal-based photosensitizers for photodynamic therapy (Room: Virtual Room) - Aug 13, 2021 - Abstract #ACSFall2021ACS_Fall_7435;
Ruthenium- and osmium-centered PSs are particularly promising, with our own TLD1433 in Phase 2 clinical trials for the treatment of bladder cancer. This presentation will focus on the design, synthesis, and characterization of a series of metal-based PSs.
- |||||||||| Photofrin (porfimer sodium) / Advanz Pharma, TLD1433 / Theralase
[VIRTUAL] Synthesis, characterization, and evaluation of a new class of metal photosensitizers (Room: Zoom Room 14) - Aug 13, 2021 - Abstract #ACSFall2021ACS_Fall_2404;
Ruthenium and osmium centered PSs serve as examples, with our own TLD1433 recently entering Phase II clinical trials for the treatment of bladder cancer. This presentation will illustrate how the rational molecular design of PSs leads to incremental improvements in PS activity for PDT.
- |||||||||| Photofrin (porfimer sodium) / Advanz Pharma, TLD1433 / Theralase
[VIRTUAL] Synthesis of pi-expansive methoxycarbonyl derivatives of Ru metal polypyridyl complexes for photodynamic therapy applications (Room: Zoom Room 14) - Aug 13, 2021 - Abstract #ACSFall2021ACS_Fall_2402;
The longer wavelength absorption helps to deep tissue penetration and will help to sensitize efficient singlet oxygen (1O2) and increase the singlet state oxygen quantum yields and ultimately lead to increase in photocytotoxicities (EC50 and PI) efficiency in PDT. Herein we explore the theme of pi-expansive methoxycarbonyl polypyridine Ru metal complexes as analogs of TLD1433 from the perspective of synthesis, characterization, and structure-activity relationships.
- |||||||||| Photofrin (porfimer sodium) / Advanz Pharma, TLD1433 / Theralase
[VIRTUAL] Dual-action metal complexes for hypoxia-active photodynamic therapy (Room: Zoom Room 14) - Aug 13, 2021 - Abstract #ACSFall2021ACS_Fall_2367;
Ruthenium- and osmium-polypyridyl complexes serve as examples, with our own TLD1433 currently undergoing a phase II clinical trial for bladder cancer. Herein, we report the development of photosensitizers active under hypoxia, one of the most challenging environments for both cancer treatment and PDT.
- |||||||||| TLD1433 / Theralase
Journal: String-Attached Oligothiophene Substituents Determine the Fate of Excited States in Ruthenium Complexes for Photodynamic Therapy. (Pubmed Central) - Aug 10, 2021
One of the complexes studied herein, Ru-ip-3T (known as TLD1433), is currently in phase II human clinical trials for treating bladder cancer by PDT...Femtosecond time-resolved transient absorption combined with resonance Raman data was used to map the excited-state relaxation processes from the Franck-Condon point of absorption to the formation of the lowest-energy triplet excited state, which is a triplet metal-to-ligand charge-transfer excited state for Ru-ip-0T-1T and an oligothienyl-localized triplet intraligand charge-transfer excited state for Ru-ip-2T-4T. We establish the structure-activity relationships with regard to changes in the excited-state dynamics as a function of thiophene chain length, which alters the photophysics of the complexes and presumably impacts the photocytotoxicity of these PSs.
- |||||||||| cisplatin / Generic mfg.
Preclinical, Journal: Rhenium-based complexes and in vivo testing: A brief history. (Pubmed Central) - Jun 30, 2021
The success of metal-based anticancer therapeutics in the treatment of cancer is best exemplified by cisplatin...This has led to investigations of other metal-based drug candidates such as auranofin, a gold-based drug candidate as well as ruthenium-based candidates, NAMI-A, NKP-1339 and TLD-1433...Another class of complexes under study are rhenium-based; such complexes have undergone extensive in vitro testing but only seven have displayed antitumor in vivo activity which is a necessary step before entering clinical trials. This present review will document, chronologically, the rhenium-based drug candidates that have undergone in vivo testing and the outlook for such complexes.
- |||||||||| TLD1433 / Theralase
[VIRTUAL] Synthesis of first row transition metal polypyridyl complexes for photodynamic therapy applications () - Mar 28, 2021 - Abstract #ACSSp2021ACS-Sp_7725;
Our TLD 1433 is an example and is the first non-tetrapyrrole metal complex PS to enter human clinical trials (currently in a Phase 2 clinical trial for treating nonmuscle invasive bladder cancer with PDT). Herein we explore a variety of first row transition metals as analogues of TLD1433 and report on their synthesis and characterization as well as structure-activity relationships.
- |||||||||| Photofrin (porfimer sodium) / Advanz Pharma
[VIRTUAL] Rational design and development of novel metal-based photosensitizers for photodynamic therapy () - Mar 28, 2021 - Abstract #ACSSp2021ACS-Sp_7705;
P2
Ruthenium- and osmium-based PSs are emerging as examples, with our own TLD1433 entering a Phase 2 clinical trial (Clinicaltrials.gov identifier NCT03945162) for the treatment of bladder cancer. Herein, we describe the rational design and development of a new class of metal-based PSs to further optimize their efficacy as PDT agents.
- |||||||||| Photofrin (porfimer sodium) / Advanz Pharma, TLD1433 / Theralase
[VIRTUAL] Exploring light-responsive metal complexes for photodynamic therapy () - Mar 28, 2021 - Abstract #ACSSp2021ACS-Sp_7697;
Osmium (Os) and ruthenium (Ru) centered PSs are emerging examples, with our own TLD1433 having recently advanced to phase II clinical trial for non-muscle invasive bladder cancer (NMIBC). Herein, we present on the design and development of several metal-based PSs and explore opportunities for enhancing their light-driven PDT effects.
- |||||||||| TLD1433 / Theralase
[VIRTUAL] Metallodrug photosensitizers for light-based cancer therapy () - Mar 28, 2021 - Abstract #ACSSp2021ACS-Sp_3826;
P2
One example is our own TLD1433, which is the first Ru-based photosensitizer to enter human clinical trials for treating cancer with PDT and is currently in a Phase II study (ClinicalTrials.gov Identifier: NCT03945162)...In this presentation, we will discuss the design and development of transition metal complex photosensitizers that exploit such pathways. The emphasis will be on the structural features and photophysical models that give rise to excited triplet states with characteristic reactivities and unique photocytotoxic effects.
- |||||||||| TLD1433 / Theralase
[VIRTUAL] Metallodrug photosensitizers for light-based cancer therapy ([Poster Session]) - Aug 20, 2020 - Abstract #ACSFall2020ACS-Fall_1496;
One example is our own TLD1433, currently in a Phase II clinical trial for treating bladder cancer with PDT...In this presentation, we will discuss the design and development of metallodrug PSs that can potentially exploit both PDT and PCT effects. The emphasis will be on the structural features and photophysical models that produce excited triplet states with characteristic reactivities.
- |||||||||| cisplatin / Generic mfg., TLD1433 / Theralase
Journal: Recent Progress in Polynuclear Ruthenium Complex-Based DNA Binders/Structural Probes and Anticancer Agents. (Pubmed Central) - Jul 16, 2020
These complexes are reviewed according to two main categories of homo-polynuclear and hetero-polynuclear complexes, each of which is further clarified into the metal centers linked by rigid and flexible bridging ligands. The perspective, challenges and future efforts for investigations into these exciting complexes are pointed out or suggested.
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