[PDF][PDF] Selective and orally bioavailable SMARCA2 targeted degraders induce synthetic lethality in SMARCA4-deficient solid tumor

K Ito, A Shvartsbart, J Rager, A Agarwal, M Hulse… - Cancer …, 2023 - preludetx.com
Conclusions▸ We have identified the first orally bioavailable bivalent molecules that
selectively degrade SMARCA2 over SMARCA4 by> 100 fold▸ Our SMARCA2 oral degrader …

Discovery of SMD-3040 as a Potent and Selective SMARCA2 PROTAC Degrader with Strong in vivo Antitumor Activity

L Yang, W Tu, L Huang, B Miao… - Journal of Medicinal …, 2023 - ACS Publications
SMARCA2 is an attractive synthetic lethality target for human cancers with SMARCA4
deficiency. Herein, we report the design, synthesis, and biological evaluation of selective …

713TiP A phase I study of PRT3789, a potent and selective degrader of SMARCA2 in patients with advanced or metastatic solid tumors and a SMARCA4 mutation

I Dagogo-Jack, A Dowlati, R Guo… - Annals of …, 2023 - annalsofoncology.org
Background Genes encoding subunits of the switch/sucrose non-fermentable (SWI/SNF)
chromatin remodeling complex are often mutated in cancer, occurring in 20% of all human …

Orally bioavailable SMARCA2 degraders with exceptional selectivity and potency

C Abbineni, LK Satyam, B Kuila, A Ettam, KA Rawoof… - Cancer Research, 2021 - AACR
Abstract Background: SMARCA2 (BRM) and SMARCA4 (BRG1) are two mutually exclusive
DNA-dependent ATPases of the SWI/SNF complex, which function in mobilizing …

Development of potent, highly selective and efficacious SMARCA2 degraders

L Yang, W Tu, L Huang, L Leng, W Jiang, M Wang… - Cancer Research, 2024 - AACR
In human lung, melanoma and other types of human cancers, the mammalian
SWItch/Sucrose Non-Fermentable (SWI/SNF) helicase SMARCA4 is frequently mutated …

Preclinical characterization of PRT7732: A highly potent, selective, and orally bioavailable targeted protein degrader of SMARCA2

A Shvartsbart, K Ito, J Rager, M Hulse, A Agarwal… - Cancer Research, 2024 - AACR
Abstract SWI/SNF (BAF) complexes play an important role in controlling gene expression by
remodeling chromatin. SMARCA2 (BRM) and SMARCA4 (BRG1) are the core catalytic …

Discovery of potent, highly selective and orally efficacious SMARCA2 degraders

L Leng, L Yang, W Tu, R Rej, SR Allu, L Huang… - Cancer Research, 2024 - AACR
In human non-small cell lung cancer, melanoma and other types of human cancers, the
mammalian SWItch/Sucrose Non-Fermentable (SWI/SNF) helicase SMARCA4 is frequently …

Abstract B113: Discovery of PRT3789, a first-in-class potent and selective SMARCA2 degrader in clinical trials for the treatment of patients with SMARCA4 mutated …

K Ito, M Hulse, A Agarwal, J Carter, M Sivakumar… - Molecular Cancer …, 2023 - AACR
SWI/SNF complexes play an important role in controlling gene expression by remodeling
chromatin. SMARCA2 (BRM) and SMARCA4 (BRG1) are the core catalytic subunits of the …

Selective PROTAC-mediated degradation of SMARCA2 is efficacious in SMARCA4 mutant cancers

J Cantley, X Ye, E Rousseau, T Januario… - Nature …, 2022 - nature.com
Abstract The mammalian SWItch/Sucrose Non-Fermentable (SWI/SNF) helicase SMARCA4
is frequently mutated in cancer and inactivation results in a cellular dependence on its …

SMARCA2/4 PROTAC for targeted protein degradation and cancer therapy

RB Kargbo - ACS Medicinal Chemistry Letters, 2020 - ACS Publications
Biological Target. SMARCA2 and SMARCA4 Summary. The SMARCA subgroup of genes
belong to the SWI1/SNF1 family that provide instructions for making chromatin remodeling …