Unlocking DCAFs To Catalyze Degrader Development: An Arena for Innovative Approaches

Q Miao, VD Kadam, A Mukherjee, Z Tan… - Journal of Medicinal …, 2023 - ACS Publications
Chemically induced proximity-based targeted protein degradation (TPD) has become a
prominent paradigm in drug discovery. With the clinical benefit demonstrated by certain …

[HTML][HTML] PELI1: key players in the oncogenic characteristics of pancreatic Cancer

X Fei, C Zhu, P Liu, S Liu, L Ren, R Lu, J Hou… - Journal of Experimental …, 2024 - Springer
Background Pancreatic cancer (PC) is a highly malignant gastrointestinal tumor, which is
characterized by difficulties in early diagnosis, early metastasis, limited therapeutic response …

The hGID GID4 E3 ubiquitin ligase complex targets ARHGAP11A to regulate cell migration

H Bagci, M Winkler, F Uliana, J Boulais, WI Mohamed… - bioRxiv, 2023 - biorxiv.org
The human CTLH/GID (hGID) complex emerged as an important E3 ligase regulating
multiple cellular processes, including cell cycle progression and metabolic activity. However …

Atomic-resolution prediction of degrader-mediated ternary complex structures by combining molecular simulations with hydrogen deuterium exchange

T Dixon, D MacPherson, B Mostofian, T Dauzhenka… - Biorxiv, 2021 - biorxiv.org
Targeted protein degradation (TPD) has emerged as a powerful approach in drug discovery
for removing (rather than inhibiting) proteins implicated in diseases. A key step in this …

[HTML][HTML] Current status of oligonucleotide-based protein degraders

PC Shih, M Naganuma, Y Demizu, M Naito - Pharmaceutics, 2023 - mdpi.com
Transcription factors (TFs) and RNA-binding proteins (RBPs) have long been considered
undruggable, mainly because they lack ligand-binding sites and are equipped with flat and …

Cullin-independent recognition of HHARI substrates by a dynamic RBR catalytic domain

KH Reiter, A Zelter, MK Janowska, M Riffle, N Shulman… - Structure, 2022 - cell.com
Summary RING-between-RING (RBR) E3 ligases mediate ubiquitin transfer through an
obligate E3-ubiquitin thioester intermediate prior to substrate ubiquitination. Although RBRs …

Targeted protein degradation via intramolecular bivalent glues

O Hsia, M Hinterndorfer, AD Cowan, K Iso, T Ishida… - bioRxiv, 2023 - biorxiv.org
Targeted protein degradation is a drug modality represented by compounds that recruit a
target to an E3 ubiquitin ligase to promote target ubiquitination and proteasomal …

Mechanism of degrader-targeted protein ubiquitinability

C Crowe, M Nakasone, S Chandler, MH Tatham… - bioRxiv, 2024 - biorxiv.org
Small molecule degraders of disease-driving proteins offer a clinically proven modality with
enhanced therapeutic efficacy and the potential to tackle previously undrugged targets …

Strategies for Conditional Regulation of Proteins

K Nadendla, GG Simpson, J Becher, T Journeaux… - JACS Au, 2023 - ACS Publications
Design of the next-generation of therapeutics, biosensors, and molecular tools for basic
research requires that we bring protein activity under control. Each protein has unique …

Probing the CRL4DCAF12 interactions with MAGEA3 and CCT5 di-Glu C-terminal degrons

GL Righetto, Y Yin, DM Duda, V Vu, MM Szewczyk… - PNAS …, 2024 - academic.oup.com
Abstract Damaged DNA-binding protein-1 (DDB1)-and CUL4-associated factor 12
(DCAF12) serves as the substrate recognition component within the Cullin4–RING E3 ligase …