Serah Kimani
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View article: OICR-41103 as a chemical probe for the DCAF1 WD40 domain
OICR-41103 as a chemical probe for the DCAF1 WD40 domain Open
Human DCAF1 is a multidomain protein that plays a critical role in protein homeostasis. Its WDR domain functions as a substrate recruitment module for RING-type CRL4 and HECT family EDVP E3 ubiquitin ligases, enabling the ubiquitination an…
View article: Discovery of an exquisitely selective WDR5 chemical probe accelerated by a high-quality DEL–ML Hit
Discovery of an exquisitely selective WDR5 chemical probe accelerated by a high-quality DEL–ML Hit Open
LH168, a potent and highly selective chemical probe for WDR5, developed based on DEL–ML (DNA encoded library–machine learning) hit.
View article: Crystal structures of DCAF1-PROTAC-WDR5 ternary complexes provide insight into DCAF1 substrate specificity
Crystal structures of DCAF1-PROTAC-WDR5 ternary complexes provide insight into DCAF1 substrate specificity Open
View article: A Target Class Ligandability Evaluation of WD40 Repeat-Containing Proteins
A Target Class Ligandability Evaluation of WD40 Repeat-Containing Proteins Open
Target class-focused drug discovery has a strong track record in pharmaceutical research, yet public domain data indicate that many members of protein families remain unliganded. Here we present a systematic approach to scale up the discov…
View article: A ligand discovery toolbox for the WWE domain family of human E3 ligases
A ligand discovery toolbox for the WWE domain family of human E3 ligases Open
The WWE domain is a relatively under-researched domain found in twelve human proteins and characterized by a conserved tryptophan-tryptophan-glutamate (WWE) sequence motif. Six of these WWE domain-containing proteins also contain domains w…
View article: Crystal structures of DCAF1-PROTAC-WDR5 ternary complexes provide insight into DCAF1 substrate specificity
Crystal structures of DCAF1-PROTAC-WDR5 ternary complexes provide insight into DCAF1 substrate specificity Open
Proteolysis-targeting chimeras (PROTACs) have been explored for the degradation of drug targets, particularly undruggable proteins, for more than two decades. They have been employed by various groups successfully, however only a handful o…
View article: A resource to enable chemical biology and drug discovery of WDR Proteins
A resource to enable chemical biology and drug discovery of WDR Proteins Open
Protein class-focused drug discovery has a long and successful history in pharmaceutical research, yet most members of druggable protein families remain unliganded, often for practical reasons. Here we combined experiment and computation t…
View article: The co-crystal structure of Cbl-b and a small-molecule inhibitor reveals the mechanism of Cbl-b inhibition
The co-crystal structure of Cbl-b and a small-molecule inhibitor reveals the mechanism of Cbl-b inhibition Open
Cbl-b is a RING-type E3 ubiquitin ligase that is expressed in several immune cell lineages, where it negatively regulates the activity of immune cells. Cbl-b has specifically been identified as an attractive target for cancer immunotherapy…
View article: Discovery of a Novel DCAF1 Ligand Using a Drug–Target Interaction Prediction Model: Generalizing Machine Learning to New Drug Targets
Discovery of a Novel DCAF1 Ligand Using a Drug–Target Interaction Prediction Model: Generalizing Machine Learning to New Drug Targets Open
DCAF1 functions as a substrate recruitment subunit for the RING-type CRL4DCAF1 and the HECT family EDVPDCAF1 E3 ubiquitin ligases. The WDR domain of DCAF1 serves as a binding platform for substrate proteins and is als…
View article: Probing the mechanism of Cbl-b inhibition by a small-molecule inhibitor
Probing the mechanism of Cbl-b inhibition by a small-molecule inhibitor Open
Cbl-b is a RING-type E3 ubiquitin ligase that is expressed in several immune cell lineages, where it negatively regulates the activity of immune cells. Cbl-b has specifically been identified as an attractive target for cancer immunotherapy…
View article: Discovery of Nanomolar DCAF1 Small Molecule Ligands
Discovery of Nanomolar DCAF1 Small Molecule Ligands Open
DCAF1 is a substrate receptor of two distinct E3 ligases (CRL4DCAF1 and EDVP), plays a critical physiological role in protein degradation, and is considered a drug target for various cancers. Antagonists of DCAF1 could be used t…
View article: The diaryl-imidazopyridazine anti-plasmodial compound, MMV652103, exhibits anti-breast cancer activity
The diaryl-imidazopyridazine anti-plasmodial compound, MMV652103, exhibits anti-breast cancer activity Open
Breast cancer is the most common malignancy in women worldwide and it remains a global health burden, in part, due to poor response and tolerance to current therapeutics. Drug repurposing, which seeks to identify new indications for existi…
View article: Targeting the Oncogenic TBX2 Transcription Factor With Chromomycins
Targeting the Oncogenic TBX2 Transcription Factor With Chromomycins Open
The TBX2 transcription factor plays critical roles during embryonic development and it is overexpressed in several cancers, where it contributes to key oncogenic processes including the promotion of proliferation and bypass of senescence. …
View article: The palladacycle complex AJ-5 induces apoptotic cell death while reducing autophagic flux in rhabdomyosarcoma cells
The palladacycle complex AJ-5 induces apoptotic cell death while reducing autophagic flux in rhabdomyosarcoma cells Open
Rhabdomyosarcoma (RMS) forms in skeletal muscle and is the most common soft tissue sarcoma in children and adolescents. Current treatment is associated with debilitating side effects and treatment outcomes for patients with metastatic dise…
View article: Managing sarcoma: where have we come from and where are we going?
Managing sarcoma: where have we come from and where are we going? Open
Sarcomas are a heterogeneous group of neoplasms of mesenchymal origin. Approximately 80% arise from soft tissue and 20% originate from bone. To date more than 100 sarcoma subtypes have been identified and they vary in molecular characteris…