TLK 286.

doi:10.2165/00126839-200405020-00011

PubMed · 15293875

TLK 286.

Abstract

TLK 286 [TELCYTA] is an antitumour agent in clinical development with Telik. It was developed through the application of Telik's proprietary TRAP chemogenomics technology. TLK 286 works by targeting tumours that overexpress glutathione S-transferase (GST) P1-1, an enzyme that has been implicated in drug resistance and poor prognosis, and is elevated in solid tumours such as head and neck, breast, gastrointestinal, lung and ovarian tumours. TLK 286 is activated by GST P1-1 and, subsequently, initiates apoptosis in targeted tumour cells. Telik owns worldwide rights to TLK 286 and intends to commercialise it in the North American market. The company plans to select a collaborator in other territories with capabilities in manufacturing, sales and marketing. Telik was previously collaborating with Taiho, Japan, on development of TLK 286, but this agreement appears to have been terminated. Telik announced in October 2002 that it had begun the first of a series of planned clinical trials of TLK 286 in combination with docetaxel in patients with non-small cell lung cancer. A phase II trial was initiated in May 2001 in patients with ovarian cancer. Two additional combination trials were initated in ovarian cancer patients in December 2002. One of the trials will evaluate the combination of TLK 286 with Doxil in patients who have failed platinum-based chemotherapy. The second trial will evaluate TLK 286 in combination with carboplatin in patients who have recurrent, platinum-sensitive ovarian cancer. Telik held a successful phase III meeting with the US FDA to discuss plans for the first registration trial of TLK 286, and in March 2003 it was announced that a phase III registration trial of TLK 286 as monotherapy had been initiated in platinum-refractory ovarian cancer patients. The multinational trial has been designated the ASSIST-1 (Assessment of Survival in Solid Tumours-1) trial. Telik plans to enrol approximately 440 women who will be assigned to either TLK 286 treatment or a control (doxorubicin liposomal or topotecan).

Explore related subjects

Animals Antineoplastic Agents Clinical Trials as Topic Glutathione Humans Mice Neoplasms Journal Article Review

Keep this discovery

Explore connections, maps & timelines

BibTeX RIS

2004. TLK 286.. https://doi.org/10.2165/00126839-200405020-00011

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2027

Protocol for Detecting and Sequencing Chikungunya Virus from Field-Collected Mosquitoes.

Arboviral diseases represent a major public health challenge, especially in tropical regions where environmental conditions may favor the proliferation and spread of mosquito vectors. Thus, early and accurate detection of chikungunya virus (CHIKV) in mosquito populations can be a valuable tool for effective surveillance of circulating variants and for identifying new viral introductions. Given the challenges of detecting arboviruses in field-captured mosquitoes, we describe an integrated workflow for CHIKV molecular detection and whole-genome sequencing. This protocol includes mosquito homogenization using a bead-based mechanical disruptor, RNA extraction using TRIzol reagent with minor modifications, molecular screening using CHIKV-specific RT-qPCR, and whole-genome amplification followed by sequencing on Illumina platforms. Despite the protocol being optimized for individual mosquitoes, it results in high-quality RNA suitable for both entomological surveillance and genomic analysis. As this protocol allows recovery of complete CHIKV genomes from mosquito specimens, it can serve as a basis for genomic epidemiology studies, enabling monitoring of viral diversity and lineage dynamics, and facilitating early detection of emerging variants to support timely and targeted public health interventions in endemic and at-risk regions.

Animals↗

PubMed2027

Genomic Profiling of Chromatin State Using CUT&Tag.

Alterations in chromatin state, mediated through histone modifications and the incorporation of histone variants, are fundamental to establishing transcriptional networks and cell identity. Recent advances in low-input epigenome profiling methods, such as CUT&Tag and CUT&RUN, have enabled the study of chromatin states from very limited starting materials. In this chapter, we describe procedures for generating CUT&Tag libraries to profile histone modifications and histone variants in early-developing zebrafish embryos.

Animals↗

PubMed2026

Relaxin-2: Shaping the Proteomic Landscape of Skeletal Muscle Physiology, Glucose Trafficking, and Mitochondrial Function in Rat.

Relaxin-2 is a hormone with robust beneficial effects on the heart and blood vessels and potential as a therapy for cardiovascular (CV) disease. Considering the interorgan communication between skeletal muscle and heart, and the relation between muscle quality/composition and CV events, we hypothesize that relaxin-2 may regulate skeletal muscle physiology and metabolism. We aim to evaluate the impact of relaxin-2 on the proteome of skeletal muscle from healthy Sprague-Dawley rats. Animals were treated with 0.4 mg/kg/day of serelaxin (recombinant form of human relaxin-2) or vehicle (PBS) for 2 weeks employing subcutaneous osmotic minipumps. Skeletal muscle protein identification and quantification were performed by LC-MS/MS using a Data-Independent Acquisition (DIA)-Sequential Window Acquisition of All Theoretical Fragment Ion Spectra (SWATH) method. SWATH/MS quantitative analysis identified that relaxin-2 significantly decreased 95 proteins and significantly increased 32 proteins in rat skeletal muscle when compared to control rats. From these, 34 proteins were associated with muscle function, myogenesis, muscle differentiation and/or regeneration, 20 are mitochondrial proteins (six from the complexes of the electron transport chain), and 10 proteins participate in glucose metabolism. Qualitative data-dependent workflow analysis identified 35 proteins exclusive to the skeletal muscle of the relaxin-2-treated group: eight proteins related to processes of skeletal muscle function (size, ion homeostasis or organization of caveolae structures and cytoskeleton) and myogenesis, and two proteins involved in muscle differentiation. Our work highlighted for the first time the role of relaxin-2 in crucial processes of muscle physiology and energetic metabolism, which could influence several processes involved in myopathy and CV.

Animals↗