nsd2

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

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

Gintemetostat (KTX-1001) is a potent and selective small molecule inhibitor of nuclear receptor-binding SET domain protein 2 (NSD2), exhibiting IC50 values ranging from 0.001 μM to 0.01 μM, and it belongs to the chemical class of piperidinyl-methyl-purineamine derivatives, with primary research applications in oncology for the treatment of NSD2-dysregulated cancers.

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

NSD2/H3K36me2 modulator-1 is an orally active modulator targeting NSD2/H3K36me2. It competitively binds to the SAM pocket of NSD2, effectively inhibiting NSD2 expression and H3K36me2 methylation. This compound can also reverse epithelial-mesenchymal transition (EMT), inhibit cell migration, and induce G0/G1 phase arrest and apoptosis (apoptosis). Additionally, NSD2/H3K36me2 modulator-1 reduces mitochondrial membrane potential (MMP) and promotes reactive oxygen species (ROS) generation. It is used in research for developing epigenetic anticancer strategies targeting NSD2 in hepatocellular carcinoma (HCC).

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-IN-5 (Compound 198) is an NSD2 inhibitor with an IC50 value ranging from 0.001 μM to 0.01 μM. It is utilized for cancer 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.

NSD2-IN-6 is a selective inhibitor of NSD2, with an IC50 of 3.8 nM for NSD2 and 274 nM for NSD1. It reduces H3K36me2 levels and reverses cellular plasticity by restoring androgen receptor (AR) signaling pathways. In organoid models, NSD2-IN-6 prompts a transition of cell states from cluster 2 and cluster 3 to cluster 1. In vivo, it exhibits antitumor activity by reversing tumor cell plasticity, inhibiting growth, and promoting apoptosis. NSD2-IN-6 is useful for research in prostate cancer.

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].

NSD2-IN-4 is a potent, selective inhibitor of the NSD2-SET domain, showing promise for the treatment of diseases related to NSD2 [1].

Lem-14-1189, a LEM-14 derivative, is a potent NSD inhibitor of the nuclear receptor binding SET domain, and has inhibitory effects on NSD1, NSD2, and NSD3, with IC50 of 418 μM, 111 μM, and 60 μM, respectively. LEM-14-1189 has potential anticancer activity and can be used to study multiple myeloma (MM) and diseases of the blood system.

W4275 (Compound 42) is a selective NSD2 inhibitor with oral activity and an IC50 of 17 nM. It exhibits antiproliferative activity, with an IC50 of 230 nM against RS411 cells, and significantly inhibits tumor growth in an RS411 tumor xenograft model. Pharmacokinetic analysis in mice shows that W4275 has a favorable oral bioavailability (F is 27.34%). W4275 holds potential for use in cancer research.

W4022 (compound 16) is an efficient dual inhibitor of the lysine methyltransferases G9a/NSD2, with IC50 values of 0.241 μM for G9a and 0.017 μM for NSD2. It exhibits potent antiproliferative properties, including the ability to suppress colony formation, induce apoptosis, and inhibit metastasis of cancer cells. W4022 effectively curtails the catalytic activities of G9a and NSD2 within cells and demonstrates significant antitumor efficacy in PANC-1 xenograft models.

UNC10415667 is an NSD2 degrader with a DC50 value of 460 nM. It is useful for research into cancers driven by NSD2 overexpression or dysregulation, including multiple myeloma, acute lymphoblastic leukemia, and prostate cancer.

Bisubstrate inhibitor 78 is an inhibitor of nicotinamide N-methyltransferase (NNMT; IC50= 1.41 μM).1It binds the NNMT active site in the binding pockets for the NNMT substrates S-adenosyl-L-methionine (SAM) and nicotinamide . Bisubstrate inhibitor 78 is selective for NNMT over histone-lysine N-methytransferase NSD2 and protein arginine methyltransferase 1 (PRMT1; IC50s = >50 μM for both). It reduces levels of 1-methylnicotinamide in, and inhibits proliferation of, HSC-2 oral cancer cells when used at a concentration of 100 μM.This compound is unstable in powder form and other related salt forms are recommended.

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.

MMSET-IN-1 is an inhibitor of multiple myeloma SET domain (MMSET, aka NSD2/WHSC1) .

NSC305787 hydrochloride ((Rac)-NSC305787 hydrochloride is a cell membrane permeable and selective and potent small molecule dual inhibitor of Cdc25 dual specificity phosphatase and EZR that displays antitumor activity in pancreatic cancer cells and inhibits Cdc25B2, Cdc25A, Cdc25B2 and Cdc25C.NSC 663284 inhibits NSD2 (IC50 of 170 nM) enzyme activity.