pwwp1

MR837 (NSD2-PWWP1 antagonist 3f) is a NSD2-PWWP1 antagonist.

BI-9321 trihydrochloride (BI9321 trihydrochloride) is a selective and potent NSD3-PWWP1 antagonist that downregulates Myc messenger RNA expression and reduces proliferation in MOLM-13 cells.

LEM-14 is a potent NSD2-specific inhibitor (IC50:132 μM).LEM-14 may be used in the study of multiple myeloma.

BI-9321 is a selective and cellular active nuclear receptor-binding SET domain 3 (NSD3)-PWWP1 domain antagonist (Kd: 166 nM). BI-9321 is inactive against NSD2-PWWP1 and NSD3-PWWP2.

UNC6934 is a chemical probe targeting the N-terminal PWWP (PWWP1) domain of NSD2.

NSD2-PWWP1-IN-3 (compound 36) is an effective inhibitor of NSD2-PWWP1, with an IC50 value of 8.05 µM. It has potential applications in cancer research.

NSD2-PWWP1-IN-2 (compound 33) is a potent NSD2-PWWP1 inhibitor, exhibiting an IC50 value of 1.49 µM, indicating its potential utility in cancer research.

NSD2-PWWP1-IN-1 (compound 31) is a potent inhibitor of NSD2-PWWP1 with an IC50 value of 0.64 µM, demonstrating potential applications in cancer research.

NSD2-PWWP1 ligand 1 (compound 34) is a small-molecule ligand that targets the NSD2-PWWP1 domain, with a potency of pIC50: 8.2. NSD2 is a large multidomain protein with functions in histone modification and reading. Dysregulation of the histone methyltransferase nuclear receptor binding SET domain 2 (NSD2) can lead to various hematological and solid malignancies. Binding of NSD2-PWWP1 ligand 1 to NSD2 reduces its enzymatic activity and inhibits tumor development.

(Rac)-NSD2-PWWP1-IN-4 (compound 7) is a potent inhibitor of NSD2-PWWP1, with IC50 and Kd values of 0.21 and 0.15 μM, respectively. This compound is useful for tumor research.

NSD2-PWWP1-IN-5 (Compound 13) is a potent inhibitor of NSD2-PWWP1, exhibiting a Kd of 78 nM. It competitively blocks NSD2-PWWP1 from recognizing H3K36me2 and DNA, thereby weakening its binding to nucleosomes. NSD2-PWWP1-IN-5 inhibits the proliferation of U2OS osteosarcoma cells and induces cell cycle arrest and apoptosis (apoptosis). This compound is useful in osteosarcoma research.

NSD2-PWWP1-IN-6 (Compound 16) is an effective NSD2-PWWP1 inhibitor with a Kd of 30 nM. It competitively blocks NSD2-PWWP1's recognition of H3K36me2 and DNA, thereby reducing its binding capacity to nucleosomes. NSD2-PWWP1-IN-6 is applicable for cancer research.

BI-9466 (Compound 2) is an antagonist of the NSD3-PWWP1 domain with a dissociation constant (Kd) of 144 µM. Designed as a negative control compound for BI-9321, BI-9466 lacks inhibitory activity against the NSD3-PWWP1 domain due to a more basic azacyclic structure introduced at the 5-position of BI-9321.

UNC10088 is a molecular glue that targets NSD2. It facilitates the formation of a stable ternary complex between SCFFBXO22 and the NSD2 PWWP1 domain. UNC10088 binds reversibly and covalently to the C326 of FBXO22, promoting the ubiquitination of the NSD2 PWWP1 domain in an SCFFBXO22-dependent manner. UNC10088 can be utilized in cancer research.

NSD2-IN-1 (compound 38) is a potent and highly selective inhibitor of NSD2-PWWP1 (nuclear receptor-binding SET domain 2-PWWP1), with an IC50 value of 0.11 μM. By binding to NSD2-PWWP1, NSD2-IN-1 influences gene expression regulated by NSD2, resulting in apoptosis and cell cycle arrest [1].

MS9715 is a potent and selective NSD3-targeting PROTAC, designed by leveraging BI-9321, which targets the PWWP1 domain of NSD3, in conjunction with an E3 ligase VHL ligand. This compound holds potential for research in NSD3-dependent cancer treatments [1].

UNC7096 is a potent, selective degrader of NSD2-PWWP1, exhibiting a dissociation constant (Kd) of 46 nM, and shows promise for treating NSD2-related diseases [1].

UNC6934 Negative Control (Axon 3591) is a chemically related compound that serves as a negative control for UNC6934, a potent and selective chemical probe that specifically targets the N-terminal PWWP (PWWP1) domain of NSD2.