Download

RIPTAC (Regulated Induced Proximity Targeting Chimeras) introduces a novel strategy that leverages induced proximity to achieve selective cancer cell killing. Using AR–BRD4 RIPTAC II-5 as a tool compound, we integrated biochemical screening, computational docking, and multi-level cellular and in vivo assays to establish a direct link between target engagement and therapeutic efficacy. Biochemical evaluation confirmed binary and ternary affinity, supported by computational simulations that predicted novel AR–BRD4 ternary protein–protein interactions (neoPPIs) consistent with cooperativity observed experimentally. II-5’s distinct slow on/off binding kinetics stabilize ternary complexes, translating into superior activity in ternary formation and downstream signaling modulation. Cellular assays demonstrated that II-5 induces ternary complexes in HEK293T AR OE, VCaP, and LNCaP cells, correlating with strong inhibition of BRD4-driven signaling (c-Myc) while only moderately inhibit AR signaling (reporter and PSA). In vivo CDX models further validated ternary complex formation, PSA reduction, and pharmacodynamic biomarker responses, showing that ternary assembly is preserved across biochemical, cellular, and tumor tissue contexts. II-5 was highly potent in AR-high prostate cancer models, with efficacy scaling across AR mutants and expression levels, highlighting a mechanistic correlation between AR expression and therapeutic effect. This enables RIPTAC to address resistance mechanisms such as AR amplification, point mutations, etc. Safety panel profiling indicates an overall favorable profile with limited off-target activity. Beyond AR–BRD4, RIPTAC expands the induced proximity landscape, aligning with TCIP paradigms and demonstrating broader applicability across oncogenic drivers. Together, computational and experimental evidence converge to highlight ternary complex stability and AR expression dependence as the mechanistic drivers of RIPTAC’s therapeutic window. Importantly, our induced proximity platform, built on extensive expertise in targeted protein degradation (TPD), can be rapidly migrated to other target pairs, enabling first-in-class drug discovery programs and supporting both domestic and international partners.

Download

Antibody-drug conjugates (ADCs) are key targeted therapies, yet drug resistance remains a major clinical challenge. To address this, we established a panel of 28 well-characterized ADC-resistant cell lines, validated via resistance profiling, RNA-seq, and WES analysis. This platform enables high-throughput screening of novel payloads and combinations to overcome resistance.

Download

Cardiac safety liability assessment is essential in drug development to prevent arrhythmias like torsades de pointes (TdP), which can cause sudden death. Traditional ICH S7B and E14 guidelines focus on hERG blockade and QT prolongation, but these lack specificity, leading to high attrition or missed risks. The Comprehensive in vitro Proarrhythmia Assay (CiPA), launched in 2013 by FDA, academia, and industry, shifts to a mechanistic paradigm. It integrates in vitro ion channel assays, in silico modeling, hiPSC-CM evaluations, and clinical ECGs to predict proarrhythmia accurately, reducing animal use and improving efficiency. Validated with 28 reference compounds, CiPA enhances specificity.

Download

Signal Transducer and Activator of Transcription 6 (STAT6) is a pivotal transcription factor activated downstream of the interleukin-4 (IL-4) and interleukin-13 (IL-13) signaling pathways. It governs the expression of key genes involved in type 2 immune responses, including Th2 cell differentiation, IgE class switching, and M2 macrophage polarization. Dysregulated STAT6 activity has been implicated in a range of diseases, from asthma and atopic dermatitis to fibrosis and immune-evasive tumors.

With the clinical advancement of STAT6-targeting drugs like Kymera’s KT-621 and Recludix’s REX-8756, the demand for precise STAT6 binding profiling is rising—supporting target validation, mechanism studies, and therapeutic development.