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-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].

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.

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.

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.

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.

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.

KTX-1001, also referred to as NSD2 inhibitor 161, is an innovative and potent inhibitor of nuclear SET domain-containing protein 2 (NSD2). This compound specifically binds to NSD2, inhibiting its catalytic activity and the mono- and dimethylation of histone H3 lysine 36 (H3K36). Such regulation impacts gene expression involved in cellular processes, including proliferation, which may subsequently slow cancer cell growth. NSD2 is part of the NSD family of histone lysine methyltransferases, which are often overexpressed and dysregulated in various cancer types.

ND-L11B is an effective degrader of the nuclear receptor binding SET domain protein 2 (NSD2) and RE-IIBP, with DC50 values of 1.48 μM and 0.8 μM, respectively, and a Dmax close to 80%.

ND-L11B TFA is a potent degrader of nuclear receptor binding SET domain protein 2 (NSD2) and RE-IIBP, with DC50 values of 1.48 μM and 0.8 μM, respectively, and a Dmax of approximately 80%.

AS-99 is a first-in-class, potent, and selective ASH1L histone methyltransferase inhibitor (IC50= 0.79 μM, Kd= 0.89 μM) with anti-leukemic activity, blocking cell proliferation, inducing apoptosis and differentiation, downregulating MLL fusion target genes, and reducing the leukemia burden in vivo[1].

AS-99 TFA is a first-in-class, potent, and selective ASH1L histone methyltransferase inhibitor (IC50= 0.79 μM, Kd= 0.89 μM) with anti-leukemic activity. It blocks cell proliferation, induces apoptosis and differentiation, downregulates MLL fusion target genes, and reduces the leukemia burden in vivo[1].

MS159 is a potent PROTAC degrader targeting the nuclear receptor binding SET structural domain protein 2 (NSD2), which inhibits tumor cell growth. This compound serves as a valuable chemical tool for investigating NSD2's function in health and disease [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].

UNC8153 TFA is a selective and potent NSD2 protein degrader with anticancer activity.UNC8153 TFA induces NSD2 degradation in MM.1S multiple myeloma cells and inhibits the proliferation of MM.1S cells.

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.

NSD-IN-3 (compound 3) serves as a potent inhibitor of the nuclear receptor binding SET domain (NSD). It effectively targets NSD2-SET and NSD3-SET, displaying IC 50 values of 0.81 μM and 0.84 μM, respectively. This compound also impedes the dimethylation of histone H3K36 and suppresses the expression of genes targeted by NSDs in non-small cell lung cancer cells. Furthermore, NSD-IN-3 promotes s-phase cell cycle arrest and induces apoptosis [1].

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.

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