Abstract 5474: QUANTROseq, a transcriptomic based drug discovery platform using time-resolved gene expression profiling: identification of inhibitors and degraders of transcription factors and cell signaling regulators

Abstract Transcription factors (TFs) and related signaling pathways have long been considered among the most challenging targets in drug discovery. To address these limitations, QUANTRO Therapeutics has developed QUANTROseq, a pioneering transcriptomic discovery platform designed to match transcriptional dynamic profiles or “fingerprints” triggered by small-molecule drug candidates with those derived from controlled, acute degradation of specific targets. This innovative approach enables the identification of novel inhibitors, modulators, and degraders with unprecedented precision and sensitivity, targeting even previously undruggable proteins. Analysis of our data demonstrated that time-resolved transcriptional profiling not only allows identification of drug candidates in HTS screening, it also reveals the mode of action of these drugs with unprecedented precision and sensitivity, provided that these act on targets that have a direct effect on transcriptional regulation, such as transcription factors (TFs) and signaling pathways (e.g. c-MYC, YAP/TEAD or KRAS). This approach allows for the clear discrimination between molecules that directly act on a specific transcription factors or directly associated regulatory co-factors, and drugs that only indirectly affect its function. The transcriptional fingerprinting approach is employed by QUANTRO at various stages of the drug discovery process: 1. Benchmarking the real mode of action of existing drugs; 2. Interrogating the efficiency, selectivity, and potency of drug candidates during Hit-validation and Hit-to-Lead optimization activities, overcoming the limitation of standard biochemical/biophysical assays in their capacity to inform regarding compounds selectivity; 3. Identifying new mode of action drug candidates that specifically interfere with disease-causing transcriptional programs in cancer, through the proprietary QUANTROseq screening platform. During last year, QUANTROseq screening technology has been employed by QUANTRO in multiple large HTS screening campaigns, which yielded high quality hits against several key oncogenic transcription factors. Screening results will be presented at the conference. Citation Format: Arianna Sabo, QUANTRO Therapeutic Team. QUANTROseq, a transcriptomic based drug discovery platform using time-resolved gene expression profiling: identification of inhibitors and degraders of transcription factors and cell signaling regulators [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5474.