PROTACs: past, present and future
Proteolysis-targeting chimeras (PROTACs) are heterobifunctional molecules consisting of
one ligand that binds to a protein of interest (POI) and another that can recruit an E3 …
one ligand that binds to a protein of interest (POI) and another that can recruit an E3 …
PROTAC targeted protein degraders: the past is prologue
Targeted protein degradation (TPD) is an emerging therapeutic modality with the potential to
tackle disease-causing proteins that have historically been highly challenging to target with …
tackle disease-causing proteins that have historically been highly challenging to target with …
Biallelic loss of BCMA as a resistance mechanism to CAR T cell therapy in a patient with multiple myeloma
BCMA targeting chimeric antigen receptor (CAR) T cell therapy has shown deep and
durable responses in multiple myeloma. However, relapse following therapy is frequently …
durable responses in multiple myeloma. However, relapse following therapy is frequently …
[HTML][HTML] Mezigdomide plus dexamethasone in relapsed and refractory multiple myeloma
PG Richardson, S Trudel, R Popat… - … England Journal of …, 2023 - Mass Medical Soc
Background Despite recent progress, multiple myeloma remains incurable. Mezigdomide is
a novel cereblon E3 ubiquitin ligase modulator with potent antiproliferative and tumoricidal …
a novel cereblon E3 ubiquitin ligase modulator with potent antiproliferative and tumoricidal …
[HTML][HTML] Expanding PROTACtable genome universe of E3 ligases
Proteolysis-targeting chimera (PROTAC) and other targeted protein degradation (TPD)
molecules that induce degradation by the ubiquitin-proteasome system (UPS) offer new …
molecules that induce degradation by the ubiquitin-proteasome system (UPS) offer new …
Functional E3 ligase hotspots and resistance mechanisms to small-molecule degraders
Targeted protein degradation is a novel pharmacology established by drugs that recruit
target proteins to E3 ubiquitin ligases. Based on the structure of the degrader and the target …
target proteins to E3 ubiquitin ligases. Based on the structure of the degrader and the target …
Alkylamine-tethered molecules recruit FBXO22 for targeted protein degradation
C Kagiou, JA Cisneros, J Farnung, J Liwocha… - Nature …, 2024 - nature.com
Targeted protein degradation (TPD) relies on small molecules to recruit proteins to E3
ligases to induce their ubiquitylation and degradation by the proteasome. Only a few of the …
ligases to induce their ubiquitylation and degradation by the proteasome. Only a few of the …
Genomic and immune signatures predict clinical outcome in newly diagnosed multiple myeloma treated with immunotherapy regimens
Despite improving outcomes, 40% of patients with newly diagnosed multiple myeloma
treated with regimens containing daratumumab, a CD38-targeted monoclonal antibody …
treated with regimens containing daratumumab, a CD38-targeted monoclonal antibody …
DCAF1-based PROTACs with activity against clinically validated targets overcoming intrinsic-and acquired-degrader resistance
Targeted protein degradation (TPD) mediates protein level through small molecule induced
redirection of E3 ligases to ubiquitinate neo-substrates and mark them for proteasomal …
redirection of E3 ligases to ubiquitinate neo-substrates and mark them for proteasomal …
Overcoming cancer drug resistance utilizing PROTAC technology
MR Burke, AR Smith, G Zheng - Frontiers in Cell and Developmental …, 2022 - frontiersin.org
Cancer drug resistance presents a major barrier to continued successful treatment of
malignancies. Current therapies inhibiting proteins indicated in cancer progression are …
malignancies. Current therapies inhibiting proteins indicated in cancer progression are …