set-2

SET 2 is an antagonist of transient receptor potential vanilloid type 2(TRPV2) with an IC50 of 0.46 μM. SET 2 shows selectivity over TRPV1, TRPV3 and TRPV4.

BMS-911543 is a potent and selective inhibitor of JAK2 with IC50 of 1.1 nM, ~350-, 75- and 65-fold selective to JAK1, JAK3 and TYK2, respectively. Phase 1/2.

CHZ868 is a type II JAK inhibitor with potential antitumor activity that reverses the persistence of type I JAK inhibitors and can be used to study leukemia.

Ribonuclease T2, Aspergillus oryzae, is a biocatalyst and a key enzyme in new biocatalyst technology. Enzyme engineering focuses on improving the kinetics of enzyme reactions, substrate selectivity, and activity under extreme conditions (e.g., low or high pH). By introducing stimuli-responsive modifications to these enzymes, dynamic control of activity is also made possible.

PFI-2 is an effective, specific and cell-active lysine methyltransferase SETD7 inhibitor (Ki/IC50: 0.33/2 nM), 1000-fold selectivity over other methyltransferases and other non-epigenetic targets.

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.

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%.

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.

JAK2-IN-7, a selective inhibitor targeting Janus Kinase 2 (JAK2), exhibits inhibitory concentrations (IC50) of 3 nM for JAK2, 11.7 nM for SET-2 cells, and 41 nM for Ba/F3 V617F cells, indicative of its potency and selectivity. This compound demonstrates more than 14-fold selectivity against JAK1, JAK3, and FLT3, underlining its specificity. JAK2-IN-7 effectively induces cell cycle arrest at the G0/G1 phase and promotes apoptosis in tumor cells, manifesting significant antitumor activities [1].

PFI-2 hydrochloride ((R)-PFI-2 hydrochloride) is a potent, highly selective, and cell-active inhibitor of the methyltransferase activity of SETD7 (IC50: 2 nM), 500 fold active than (S)-PFI-2.

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].

NMS-P953 is a JAK2 inhibitor, displaying significant tumor growth inhibition in SET-2 xenograft tumor model. NMS-P953 has a mechanism of action confirmed in vivo by typical modulation of known biomarkers, and with a favorable pharmacokinetic and safety profile.

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].

DC 432, a potent peptidomimetic inhibitor of N-terminal methyltransferase 1/2 (NTMT1/2) with an IC50 value of 54 nM, incorporates a BM30 peptide enhanced by five arginine residues. It effectively reduces the N-terminal methylation level of the regulator of chromosome condensation 1 and SET proteins in HCT116 cells, demonstrating cell permeability.

ssK36 is a super-substrate peptide derived from the histone methyltransferase (SET) domain protein 2 (SETD2). This peptide was specifically designed for SETD2, a unique PKMT responsible for methylating the 36th lysine residue on histone H3 (H3K36) in human cells, resulting in H3K36me3. Remarkably, ssK36 undergoes methylation by SETD2 at a rate over 100 times faster than the natural substrate H3K36. ssK36 serves as a valuable tool for investigating the catalytic mechanisms of PKMTs, particularly regarding substrate specificity and catalytic efficiency.