ACBI1 / Boehringer Ingelheim - LARVOL DELTA

Beyond Barriers, Big Crystallization Hurdles: Atropisomerism in Beyond Rule of Five Compounds Explored by Computational and NMR Studies. (PubMed, Mol Pharm) - "In this study, we explore the intricate interplay between atropisomerism and crystallization using two model bRo5 compounds, namely, ACBI1 and BI201335, both violating three of four Lipinski's rules. This comprehensive analysis highlights the significance of understanding stereochemical phenomena such as atropisomerism in designing and developing bRo5 compounds. By integrating advanced analytical techniques and crystallization strategies, this work provides novel insights into tailoring pharmaceutical properties for next-generation therapeutics."

Journal

SMARCA4-driven oncogenic enhancer and transcriptional reprogramming in non-small cell lung cancer (AACR 2025) - "Furthermore, targeting SMARCA4 with small molecules such as BRM014 and ACBI1 selectively impaired cell viability in SMARCA4-restored cells, underscoring their potential as therapeutic agents for SMARCA4-dependent cancers. These findings reveal a central role for SMARCA4 in epigenetic regulation and enhancer activation, driven by the SMARCA4/FOSL1 axis, and offer insights into potential therapeutic strategies for NSCLC."

Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • FOSL1 • SMARCA4

MYC-mediated resistance to immune activation by SWI/SNF mutation or chemical inhibition (AACR 2025) - "SWI/SNF ATPase inhibitors (FHD-286, BRD98, and BRM014) and degraders (ACBI1) similarly induce ISGs through a cGAS/STING-dependent mechanism. This study highlights the suppressive effect of MYC overexpression on IFN-I responses in ARID1A-deficient cancers and suggests a potential link to therapeutic resistance in MYC-high tumors. While the precise molecular mechanisms remain to be fully elucidated, these findings provide a foundation for future studies aimed at understanding the interplay between oncogenic drivers and immune signaling pathways, with implications for developing more effective therapeutic strategies."

Oncology • ARID1A • CD8 • CTNNB1 • KRAS • MYC • STING

Modeling the Effect of Cooperativity in Ternary Complex Formation and Targeted Protein Degradation Mediated by Heterobifunctional Degraders. (PubMed, ACS Bio Med Chem Au) - "We also develop a statistical inference model for determining cooperativity in intracellular ternary complex formation from cellular assay data and demonstrate it by quantifying the change in cooperativity due to site-directed mutagenesis at the POI-ligase interface of the SMARCA2-ACBI1-VHL ternary complex. Our pharmacodynamic model provides a quantitative framework to dissect the complex HBF-mediated TPD process and may inform the rational design of effective HBF degraders."

Journal • Targeted Protein Degradation • SMARCA2

[VIRTUAL] A mutation characteristics analysis of SMARCA4defSMARCA2wt in lung cancer (ESMO 2021) - "Selective SMARCA2 degrading agents (such as ACBI1, one of PROTAC drugs) can induce the death of SMARCA4-deficient cancer cells... Our analysis indicate the medication-related mutation characteristics of SMARCA4defSMARCA2wt in lung cancer, and may contribute to medication guidance."

IO biomarker • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • BRAF • EGFR • KRAS • ROS1 • SMARCA2 • SMARCA4 • TMB

"New PK data on OpnMe portal qualifies the Smarca2/4 (Brg1/Brm) degrader ACBI1 as appropriate for in vivo studies. Sharing this data enables the field to make best use of the compound #openaccess @Boehringer @UoDLifeSciences" (@alessiociulli)

PK/PD data • Preclinical • SMARCA2 • SMARCA4

"#RESEARCHERS: Check #opnMe for new data for an expanded use of the ACBI1 PROTAC jointly developed with @alessiociulli @dundeeuni" (@Boehringer)

Targeted Protein Degradation