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Chemical Structure| 89795-81-3 Chemical Structure| 89795-81-3

Structure of 89795-81-3

Chemical Structure| 89795-81-3

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McGrath, Andrew ; Huang, Haiyan ; Brazeau, Jean-Francois ; Zhang, Zirong ; Audu, Christopher O ; Vellore, Nadeem A , et al.

Abstract: Protein degradation using proteolysis targeting chimeras (PROTACs) represents a promising therapeutic strategy. PROTACs are heterobifunctional molecules that consist of a target-binding moiety and an E3 ligase binding moiety, connected by a linker. These fragments are frequently united via amide bonds. While straightforward to synthesize, amides may impart suboptimal drug properties to the overall molecule. From a systems level perspective, we envisioned that the potency of PROTACs could be modulated through selection of reaction conditions-wherein different catalysts produce distinct linkers from the same two building blocks. We present a suite of BRD4 PROTAC degraders prepared via four new amine−acid coupling reactions alongside the classic amide coupling. Our findings reveal that variations in reaction conditions affect the physicochemical properties of PROTACs, resulting in a spectrum of properties. Notably, several new PROTACs demonstrated enhanced BRD4 degradation efficacy compared to those employing amide linkers, emphasizing the potential of systems chemistry as a therapeutic optimization strategy.

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Product Details of [ 89795-81-3 ]

CAS No. :89795-81-3
Formula : C7H6N4
M.W : 146.15
SMILES Code : N#CNC(=N)C1=NC=CC=C1
MDL No. :MFCD24386261
InChI Key :HMQYOLLIJRIQNB-UHFFFAOYSA-N
Pubchem ID :22416565

Safety of [ 89795-81-3 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H315-H319-H335
Precautionary Statements:P261-P264-P271-P280-P302+P352-P304+P340-P305+P351+P338-P312-P362-P403+P233-P501
 

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