Ziemowit_Pokladek

Medicinal Chemist in TPD field | Opinions are my own

[Radek Nowak @RPNowak]

Targeted protein #degradation: from mechanisms to #clinic. New molecular mechanisms can rapidly be translated - we can learn so much from nature.
Great to be able to share this piece with @jonathanMtsai Ben Ebert and Eric Fischer @fischerlab1. #TPD https://t.co/Czk3aeQ7td

[Ziemowit_Pokladek @ZPokladek]

📚💡Linker-free PROTACs efficiently induce the degradation of oncoproteins

https://t.co/FQeXkqiPc7

#TPD #Targeted_Protein_Degradation #PROTAC

[Ziemowit_Pokladek @ZPokladek]

❗ 📚💡A comprehensive mechanistic investigation of factors affecting intestinal absorption and bioavailability of two PROTACs in rats

https://t.co/SM0N0mZWAV

#TPD #Targeted_Protein_Degradation

#CRBN

[Ziemowit_Pokladek @ZPokladek]

📚💡Proteome-Wide Discovery of Degradable Proteins Using Bifunctional Molecules from AbbVie

https://t.co/Cu6IuUcB59

#TPD #Targeted_Protein_Degradation

[Ziemowit_Pokladek @ZPokladek]

📚Equilibrium Drives Cyclosporine Membrane Permeability: The Goldilocks Energy Barriers

https://t.co/meai19ubyW

#permeability

[Ziemowit_Pokladek @ZPokladek]

❗📚💡Discovery of Daraxonrasib (RMC-6236), a Potent and Orally Bioavailable RAS(ON) Multi-selective, Noncovalent Tri-complex Inhibitor for the Treatment of Patients with Multiple RAS-Addicted Cancers from Revolution Medicines

https://t.co/Bvq1jNpV4E

[Ziemowit_Pokladek @ZPokladek]

❗ 📚💡 PK/PD modeling of targeted protein degraders: Charting new waters and navigating the shallows

https://t.co/OxJ4jNoISM

#TPD #Targeted_Protein_Degradation

[Ziemowit_Pokladek @ZPokladek]

📚Leveraging Structural and Computational Biology for Molecular Glue Discovery

https://t.co/mQx0mC5R2x

#TPD #Targeted_Protein_Degradation

[Ziemowit_Pokladek @ZPokladek]

📚 Structures of the 26S proteasome in complex with the Hsp70 cochaperone Bag1 reveal a novel mechanism of ubiquitin-independent proteasomal degradation

https://t.co/XVZe5HXDJW

#TPD #Targeted_Protein_Degradation

[Ziemowit_Pokladek @ZPokladek]

📚 Design and Discovery of Preclinical Candidate LYG-409 as a Highly Potent and Selective GSPT1 Molecular Glue Degraders

https://t.co/OE9BE8BDpx

#TPD #Targeted_Protein_Degradation #CRBN #GSPT1

[Ziemowit_Pokladek @ZPokladek]

📚💡 Replacing a Cereblon Ligand by a DDB1 and CUL4 Associated Factor 11 (DCAF11) Recruiter Converts a Selective Histone Deacetylase 6 PROTAC into a pan-degrader

https://t.co/BWReYnT9aO

#TPD #Targeted_Protein_Degradation

[Ziemowit_Pokladek @ZPokladek]

📚💡 E2–Ub-R74G strategy reveals E2-specific ubiquitin conjugation profiles in live cells

https://t.co/cgiZNJPyU8

#TPD #Targeted_Protein_Degradation #E2

[Ziemowit_Pokladek @ZPokladek]

❗📚💡 The efflux pump ABCC1/MRP1 constitutively restricts PROTAC sensitivity in cancer cells from CeMM and Centre for Targeted Protein Degradation

https://t.co/Kd6VjwaQr0

#TPD #Targeted_Protein_Degradation

[Ziemowit_Pokladek @ZPokladek]

📚 Temporal and Spatial Characterization of CUL3KLHL20-driven Targeted Degradation of BET family, BRD Proteins by the Macrocycle-based Degrader BTR2004

https://t.co/hZZNF2ehlY

#TPD #Targeted_Protein_Degradation

[Ziemowit_Pokladek @ZPokladek]

📚💡Frustration in the Protein-Protein interface Plays a Central Role in the Cooperativity of PROTAC Ternary Complexes

https://t.co/uxb2cHBSeY

#TPD #Targeted_Protein_Degradation

[Ziemowit_Pokladek @ZPokladek]

❗ 📚💡A Kinetic Scout Approach Accelerates Targeted Protein Degrader Development

#TPD #Targeted_Protein_Degradation

[Ziemowit_Pokladek @ZPokladek]

📚💡 Degrading the key component of the inflammasome: Development of an NLRP3 PROTAC

https://t.co/TeYjT7kXzm

#TPD #Targeted_Protein_Degradation #Protac

[Ziemowit_Pokladek @ZPokladek]

Crystal structures of DCAF1-PROTAC-WDR5 ternary complexes provide insight into DCAF1 substrate specificity

https://t.co/Wp3Tvqgjjz

#TPD #Targeted_Protein_Degradation #PROTAC #TCF

[Ziemowit_Pokladek @ZPokladek]

📚💡 Covalent Targeting of Histidine Residues with Aryl Fluorosulfates: Application to Mcl-1 BH3 Mimetics

https://t.co/Dx8r2hGCDa

#Covalent

[Ziemowit_Pokladek @ZPokladek]

❗❗ 📚💡 Structural basis for C-degron selectivity across KLHDCX family E3 ubiquitin ligases

https://t.co/qDJgYfE3kD

#TPD #Targeted_Protein_Degradation