UNC9036 

UNC9036 is a PROTAC-based STING degrader, with a DC₅₀ of 227 nM. UNC9036-mediated STING degradation is proteasome and VHL dependent (Structure Note: Red, STING agonist diABZI (HY-112921A); Blue, VHL ligand VH032 (HY-120217); Black, linker)^[1].

UNC9036 mediated degradation occurs through a multistep mechanism;
The diABZI PROTAC binds and activates STING, activated STING is phosphorylated;
The VHL ligand recruits VHL to target phosphorylated STING for proteasomal degradation.
VHL depletion partially rescues STING expression under UNC9036 treatment conditions^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

1418.71

C₇₃H₉₅N₁₇O₁₁S

O=C(NCCCCCCCCC(N[C@@H](C(N1[C@H](C(NCC2=CC=C(C=C2)C3=C(C)N=CS3)=O)C[C@H](C1)O)=O)C(C)(C)C)=O)C4=CC5=C(C(OC)=C4)N(C/C=C/CN6C(NC(C7=CC(C)=NN7CC)=O)=NC8=C6C(OCCCN9CCOCC9)=CC(C(N)=O)=C8)C(NC(C%10=CC(C)=NN%10CC)=O)=N5

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• [1]. Zhichuan Zhu, et al. Development of VHL-recruiting STING PROTACs that suppress innate immunity. Cell Mol Life Sci. 2023 May 14;80(6):149.  [Content Brief]