[PDF][PDF] Inducible degradation of target proteins through a tractable affinity-directed protein missile system

LM Simpson, TJ Macartney, A Nardin, LJ Fulcher… - Cell Chemical …, 2020 - cell.com
The affinity-directed protein missile (AdPROM) system utilizes specific polypeptide binders
of intracellular proteins of interest (POIs) conjugated to an E3 ubiquitin ligase moiety to …

Targeting endogenous proteins for degradation through the affinity-directed protein missile system

LJ Fulcher, LD Hutchinson, TJ Macartney… - Open …, 2017 - royalsocietypublishing.org
Targeted proteolysis of endogenous proteins is desirable as a research toolkit and in
therapeutics. CRISPR/Cas9-mediated gene knockouts are irreversible and often not feasible …

[PDF][PDF] Targeting endogenous K-RAS for degradation through the affinity-directed protein missile system

S Röth, TJ Macartney, A Konopacka, KH Chan… - Cell Chemical …, 2020 - cell.com
K-RAS is known as the most frequently mutated oncogene. However, the development of
conventional K-RAS inhibitors has been extremely challenging, with a mutation-specific …

An affinity-directed protein missile system for targeted proteolysis

LJ Fulcher, T Macartney, P Bozatzi… - Open …, 2016 - royalsocietypublishing.org
The von Hippel–Lindau (VHL) protein serves to recruit the hypoxia-inducible factor alpha
(HIF1α) protein under normoxia to the CUL2 E3 ubiquitin ligase for its ubiquitylation and …

Development of BromoTag: a “bump-and-hole”–PROTAC system to induce potent, rapid, and selective degradation of tagged target proteins

AG Bond, C Craigon, KH Chan, A Testa… - Journal of Medicinal …, 2021 - ACS Publications
Small-molecule-induced protein depletion technologies, also called inducible degrons,
allow degradation of genetically engineered target proteins within cells and animals. Here …

Covalently engineered nanobody chimeras for targeted membrane protein degradation

H Zhang, Y Han, Y Yang, F Lin, K Li… - Journal of the …, 2021 - ACS Publications
The targeted degradation of membrane proteins would afford an attractive and general
strategy for treating various diseases that remain difficult with the current proteolysis …

In vivo knockdown of pathogenic proteins via specific and nongenetic inhibitor of apoptosis protein (IAP)-dependent protein erasers (SNIPERs)

N Ohoka, K Okuhira, M Ito, K Nagai, N Shibata… - Journal of Biological …, 2017 - ASBMB
Many diseases, especially cancers, result from aberrant or overexpression of pathogenic
proteins. Specific inhibitors against these proteins have shown remarkable therapeutic …

Development of a small hybrid molecule that mediates degradation of His-Tag fused proteins

K Okitsu, T Hattori, T Misawa, T Shoda… - Journal of Medicinal …, 2018 - ACS Publications
In recent years, the induction of target–protein degradation via the ubiquitin–proteasome
system (UPS) mediated by small molecules has attracted attention, and this approach has …

[HTML][HTML] SNIPERs—Hijacking IAP activity to induce protein degradation

M Naito, N Ohoka, N Shibata - Drug Discovery Today: Technologies, 2019 - Elsevier
The induction of protein degradation by chimeric small molecules represented by proteolysis-
targeting chimeras (PROTACs) is an emerging approach for novel drug development. We …

Bifunctional small molecules that mediate the degradation of extracellular proteins

DF Caianiello, M Zhang, JD Ray, RA Howell… - Nature Chemical …, 2021 - nature.com
Targeted protein degradation (TPD) has emerged as a promising therapeutic strategy. Most
TPD technologies use the ubiquitin–proteasome system, and are therefore limited to …