SGC707 is a first-in-class PRMT3 chemical probe which is a potent, selective, and cell-active allosteric inhibitor of PRMT3 with IC50 of 31 nM.IC50 value: 31 nMTarget: PRMT3in vitro: SGC707 is the first PRMT3 chemical probe. SGC707 is a potent PRMT3 inhibitor (IC50=31±2 nM, KD=53±2 nM) with outstanding selectivity (selective against 31 other methyltransferases and more than 250 non-epigenetic targets). SGC707 can engage PRMT3 and effectively inhibit its catalytic activity in cells and that overexpressed PRMT3 can methylate histone H4 in cells. SGC707 stabilizes PRMT3 in both HEK293 and A549 cells with EC50 values of 1.3 μM and 1.6 μM in PRMT3 InCELL Hunter Assays.in vivo: SGC707 is bioavailable and suitable for animal studies. This well characterized chemical probe is an excellent tool to further study the role of PRMT3 in health and disease. We assessed in vivo pharmacokinetic (PK) properties of SGC707. Intraperitoneal injection of SGC707 at 30 mg/kg gave good plasma exposure in CD-1 male mice over 6 h with the peak plasma level of 38000 nM. The plasma level of SGC707 at 6 h post injection was 208 nM, more than 2-fold higher than its IC50 value in the cellular assay and the half-life of SGC707 was about 1 h. This mdose was well tolerated by the test animals. These results suggest that SGC707 is suitable for animal studies in addition to cell-based studies.
JQAD1 is a CRBN-dependent PROTAC that selectively targets EP300 for degradation. JQAD1 suppresses EP300 expression and the H3K27ac modification. JQAD1 induces apoptosis. JQAD1 can be used in research of cancer[1].
Aurora Kinases-IN-4 (Compound 11c) is a covalent and ATP competitive aurora kinase A inhibitor (IC50: 1.7 nM). Aurora Kinases-IN-4 inhibits cell proliferation in SJSA-1, MDA-MB-231, A54, HeLa cells with IC50s of 4.27, 1.54, 3.08, 6.99 μM. Aurora Kinases-IN-4 can be used for research of triple negative breast cancer (TNBC)[1].
AMPK activator 10 is an orally active, potent AMPK activator with EC150 of 44.3 nM by cell-ELISA. AMPK activator 10 increases the phosphorylation levels of ACC. AMPK activator 10 exhibits a glucose lowering effect[1].
YF-2 is a highly selective, blood-brain-barrier permeable histone acetyltransferase activator, acetylates H3 in the hippocampus, with EC50s of 2.75 μM, 29.04 μM and 49.31 μM for CBP, PCAF, and GCN5, respectively, shows no effect on HDAC. Anti-cancer and anti-Alzheimer's disease[1].
2-Methylquinazolin-4-ol is a potent competitive poly(ADP-ribose) synthetase inhibitor, with a Ki of 1.1 μM. 2-Methylquinazolin-4-ol mammalian aspartate transcarbamylase (ATCase) inhibitor, with 0.20 mM[1][2].
Pseudoprotodioscin, a furostanoside, inhibits SREBP1/2 and microRNA 33a/b levels and reduces the gene expression regarding the synthesis of cholesterol and triglycerides[1].
PCAF-IN-2 (compound 17) is a potent PCAF inhibitor with an IC50 value of 5.31 µM. PCAF-IN-2 shows anti-tumour activity. CAF-IN-2 induces apoptosis and arrest the cell cycle at the G2/M phase[1].
AMPK activator 2 (compound 7a), a fluorine-containing proguanil derivative, up-regulates AMPK signal pathway and downregulates mTOR/4EBP1/p70S6K. AMPK activator 2 inhibits proliferation and migration of human cancer cell lines (UMUC3, T24, A549)[1].
Scopolin is a coumarin isolated from Arabidopsis thaliana (Arabidopsis) roots[1]. Scopolin attenuated hepatic steatosis through activation of SIRT1-mediated signaling cascades[2].
Tazemetostat trihydrochloride (EPZ-6438 trihydrochloride) is a potent, selective and orally available EZH2 inhibitor. Tazemetostat trihydrochloride inhibits the activity of human polycomb repressive complex 2 (PRC2)-containing wild-type EZH2 with a Ki of 2.5 nM. Tazemetostat trihydrochloride inhibits EZH2 with IC50s of 11 and 16 nM in peptide assay and nucleosome assay, respectively. Tazemetostat trihydrochloride inhibits rat EZH2 with an IC50 of 4 nM. Tazemetostat (EPZ-6438) also inhibits EZH1 with an IC50 of 392 nM[1].
SIRT2-IN-10 (Compound 12) is a potent SIRT2 inhibitor with an IC50 of 1.3 μM. SIRT2-IN-10 can be used for the research of cancer and neurodegenerative disease[1].
Olaparib (AZD2281;KU0059436) is a potent and oral PARP inhibitor with IC50s of 5 and 1 nM for PARP1 and PARP2, respectively.
[Ser25] Protein Kinase C (19-31) is a substrate of protein kinase C (PKC) (Km: 0.3 μM). [Ser25] Protein Kinase C (19-31) is derived from the pseudo-substrate regulatory domain of PKCα (19-31) with a Serine at position 25 replacing the wild-type Alanine[1].
DPPY (compound 6) is a potent PTK inhibitor with IC50 values of <10, <10, <10 nM for EGFR, BTK, JAK3, respectively. DPPY shows anti-proliferative activity against B-cell lymphoma cells. DPPY has the potential for the research of idiopathic pulmonary fibrosis (IPF)[1].
TK4g is a Janus kinase (JAK) inhibitor with the IC50 values of 12.61 nM and 15.80 nM for JAK2 and JAK3, respectively. TK4g can be used in lymphoid-derived diseases and leukemia cancer research[1].
Boc-Lys(Ac)-AMC is a cell-permeable fluorometric HDAC substrate (Ex/Em = 355 nm/460 nm)[1][2].
(Rac)-Ruxolitinib D9 ((Rac)-INCB18424 D9) is the deuterium labeled (Rac)-Ruxolitinib. (Rac)-Ruxolitinib is a JAK2 inhibitor[1].
Brevilin A is a sesquiterpene lactone isolated from Centipeda minima with anti-tumor activity. Brevilin A is a selective inhibitor of JAK-STAT signal pathway by attenuating the JAKs activity and blocking STAT3 signaling (IC50 = 10.6 µM) in Cancer Cells. Brevilin A induces apoptosis and autophagy via mitochondrial pathway and PI3K/AKT/mTOR inactivation in colon adenocarcinoma cell CT26[1][2].
Xanthoangelol, extracted from Angelica keiskei, suppresses obesity-induced inflammatory responses. Xanthoangelol possesses antibacterial activity[1][2]. Xanthoangelol and inhibits monoamine oxidases[3]. Xanthoangelol induces apoptosis in neuroblastoma and leukemia cells[4].
Ruxolitinib phosphate is a potent JAK1/2 inhibitor with IC50s of 3.3 nM/2.8 nM, respectively, showing more than 130-fold selectivity over JAK3.
9-Hydroxyoctadecanoic acid (9-HSA) is an HDAC1 inhibitor that inhibits ∼66.4% HDAC1 enzymatic activity at 5 μM. 9-Hydroxyoctadecanoic acid shows anticancer activity[1].
Suberoyl bis-hydroxamic acid (Suberohydroxamic acid; SBHA) is a competitive and cell-permeable HDAC1 and HDAC3 inhibitor with ID50 values of 0.25 μM and 0.30 μM, respectively[1].Suberoyl bis-hydroxamic acid renders MM cells susceptible to apoptosis and facilitates the mitochondrial apoptotic pathways[2].Suberoyl bis-hydroxamic acid can be used for the study of medullary thyroid carcinoma (MTC)[3].
ARTD10/PARP10-IN-1 (compound 23) is a potent and non-selective PARP inhibitor, targeting to mono-ADP-ribosyltransferases ARTD7/PARP15, ARTD8/PARP14, ARTD10/PARP10 and poly(ADP-ribose) polymerase-1 (ARTD1/PARP1) with IC50s of 1.7 μM, 1.6 μM, 0.8 μM, and 4.4 μM, respectively[1].
6-Demethoxytangeretin is a citrus flavonoid isolated from Citrus depressa. 6-Demethoxytangeretin exerts anti-inflammatory activity and anti-allergic activity, suppresses production and gene expression of interleukin-6 in human mast cell-1 via anaplastic lymphoma kinase (ALK) and mitogen-activated protein kinase (MAPK) pathways[1]. 6-Demethoxytangeretin facilitates the CRE-mediated transcription associated with learning and memory in cultured hippocampal neurons[2].
NCGC00244536 is a potent KDM4B inhibitor with an IC50 of 10 nM.
Tanshindiol C is a S-adenosylmethionine-competitive EZH2 (Histone Methyltransferase) inhibitor with an IC50 of 0.55 μM for inhibiting the methyltransferase activity. Tanshindiol C is also an activator of both Nrf2 and Sirtuin 1 (Sirt1) in macrophages. Tanshindiol C possesses anti-cancer activity, and can be used for atherosclerosis research[1][2].
Dot1L-IN-1 is a highly potent, selective and structurally novel Dot1L inhibitor with a Ki of 2 pM.
MI-2-2 is a potent menin-MLL inhibitor. MI-2-2 binds to menin with low nanomolar affinity (Kd=22nM) and very effectively disrupts the bivalent protein-protein interaction between menin and MLL. MI-2-2 has specific and very pronounced activity in MLL leukemia cells, including inhibition of cell proliferation, down-regulation of Hoxa9 expression, and differentiation[1].
NCC-149 is a selective HDAC8 inhibitor and can be used for neural differentiation research[1].