Semagacestat is a γ-secretase inhibitor, inhibits β-amyloid (Aβ42), Aβ38 and Aβ40 with IC50 of 10.9, 12 and 12.1 nM, respectively; also inhibits Notch signaling with IC50 of 14.1 nM.
Berberine has shown to be effective in inhibiting cell proliferation and promoting apoptosis in various cancerous cells; MAPK and Wnt/β-catenin pathways affected by Berberine.IC50 value:Target: Anticancer agentThe plant-based alkaloid berberine has potential therapeutic applications for breast cancer, although a better understanding of the genes and cellular pathways regulated by this compound is needed to define the mechanism of its action in cancer treatment. In this review, the molecular targets of berberine in various cancers, particularly breast cancer, are discussed. Berberine was shown to be effective in inhibiting cell proliferation and promoting apoptosis in various cancerous cells. Some signaling pathways affected by berberine, including the MAP (mitogen-activated protein) kinase and Wnt/β-catenin pathways, are critical for reducing cellular migration and sensitivity to various growth factors [1]. Treatment with BBR(Berberine) in rats on the atherogenic diet reduced plasma total cholesterol and nonHDL cholesterol levels by 29%-33% and 31%-41%, respectively, with no significant differences being observed among the three doses [2]. Berberine induced both apoptotic and autophagic death of HepG2 cells, which was associated with a significant activation of AMPK and an increased expression of the inactive form of acetyl-CoA carboxylase (ACC) [3]. Berberine did not show major effects on viability of HEK-293 embryonic kidney and HCT116 colon carcinoma cells and was not toxic in concentrations up to 20 μM. Berberine inhibited β-catenin transcriptional activity and attenuated anchorage-independent growth. As a result of berberine treatment, cellular levels of active β-catenin were reduced concomitant with an increase in the expression of E-cadherin [4].
LY-411575 is a potent γ-secretase inhibitor with IC50 of 0.078 nM/0.082 nM (membrane/cell-based), and also inhibits Notch S3 cleavage with IC50 of 0.39 nM.
IHMT-MST1-58 is a potent, selective mammalian and orally active STE20-like protein 1 kinase (MST1) inhibitor with IC50 value of 23 nM. IHMT-MST1-58 can be used for the research of Type 1/2 diabetes[1].
Eucannabinolide is a STAT3 inhibitor. Eucannabinolide suppresses STAT3 activation at tyrosine 705, inhibiteds its translocation to nucleus, and decreases its DNA binding capacity. Eucannabinolide can be used for triple negative breast cancer (TNBC) diseases research[1].
Niclosamide-13C6 (monohydrate) is the 13C labeled Niclosamide monohydrate[1]. Niclosamide (BAY2353) monohydrate is an orally active antihelminthic agent used in parasitic infection research[2]. Niclosamide monohydrate is a STAT3 inhibitor with an IC50 of 0.25 μM in HeLa cells[5]. Niclosamide monohydrate has biological activities against cancer, and inhibits DNA replication in Vero E6 cells[3][4][6].
I-287 is a potent, selective, orally active inhibitor of PAR2, negative PAR2 allosteric modulator, inhibits PAR2-mediated activation of Gq and G12/13 but not Gi/o proteins (IC50=45-390 nM);I-287 is a negative allosteric modulator (NAM) and not an orthosteric competitive antagonist of hPAR2.I-287 inhibits PAR2-mediated activation of DAG/Ca2+/PKC and RhoA/SRF-RE, as well as FAK and ERK1/2 signaling pathways, shows no effect on PAR2-mediated recruitment of βarrestin2 and receptor internalization.I-287 inhibits PAR2-induced secretion of IL-8 cytokine in vitro and reduces Freund's adjuvant (CFA)-induced paw edema model in mice.
3,7-DMF is an orally active inhibitor of TGF-β1-induced activation of HSCs. 3,7-DMF induces antioxidant genes and quenches ROS away, which can be used to study liver fibrosis[1].
YAP-TEAD-IN-1 is a potent and competitive inhibitor of YAP–TEAD interaction (IC50=25 nM). YAP-TEAD-IN-1 is a 17mer peptide and shows a higher the binding affinity to TEAD1 (Kd=15 nM) than YAP (50-171) (Kd=40 nM)[1].
Tetramethylcurcumin (FLLL31), derived from curcumin, specifically suppresses the phosphorylation of STAT3 by binding selectively to Janus kinase 2 and the STAT3 Src homology-2 domain. Tetramethylcurcumin exhibits anti-inflammatory and anti-cancer effects[1][2].
Sugiol is an abietane diterpenoid, can be isolated from Calocedrus formosana bark. Sugiol has anti-inflammatory activity, could effectively reduce intracellular reactive oxygen species (ROS) production in lipopolysaccharide (LPS)-stimulated macrophages[1].
Casein Kinase 2 Substrate Peptide is a common CK2 substrate peptide. Casein Kinase 2 Substrate Peptide is synthesized with its C-terminus conjugated to 5-[(2-aminoethyl)amino]naphthalene-1-sulfonic acid (EDANS). Casein Kinase 2 Substrate Peptide can be used for protein kinase CK2 activity determination[1].
BML-284 is selective and cell-permeable Wnt signaling activator.
Hydrochlorothiazide-13C6 is the 13C labeled Hydrochlorothiazide[1]. Hydrochlorothiazide (HCTZ), an orally active diuretic drug of the thiazide class, inhibits transforming TGF-β/Smad signaling pathway. Hydrochlorothiazide has direct vascular relaxant effects via opening of the calcium-activated potassium (KCA) channel. Hydrochlorothiazide improves cardiac function, reduces fibrosis and has antihypertensive effect[2][3][4].
RO8191 (RO4948191), an imidazonaphthyridine compound, is an orally active and potent interferon (IFN) receptor agonist. RO8191 activates IFN-stimulated genes (ISGs) expression and JAK/STAT phosphorylation. RO8191 shows antiviral activity against both HCV and EMCV with an IC50 of 200 nM for HCV replicon[1].
Exoenzyme C3, clostridium botulinum is a promising agent to inactivate RhoA in neurons due to preventing the detrimental effect of active Rho in the recovery of injured neuronal systems. Exoenzyme C3, clostridium botulinum is used for the study of post-traumatic neuro-regeneration[1].
Cotosudil is a ROCK kinase inhibitor, which can be used for glaucoma or ocular hypertension research[1].
Purmorphamine is a smoothened receptor agonist with an EC50 of 1 μM.
ROCK2-IN-6 hydrochloride (Comp A) is a selective ROCK2 inhibitor, can be used for ROCK mediated diseases, autoimmune diseases and inflammation research[1].
20(S)-hydroxyCholesterol (20α-Hydroxycholesterol) is an allosteric activator of the oncoprotein smoothened (Smo) that activates the hedgehog (Hh) signaling pathway with an EC50 of 3 μM in a gene transcription reporter assay using NIH3T3 cells[1][2].
ARN25068 is a sub-micromolar inhibitor of the three protein kinases, GSK-3β, FYN and DYRK1A to tackle tau hyperphosphorylation[1].
Tyk2-IN-8 (Compound 3) is a selective Tyk-2 inhibitor with an IC50 of 5.7 nM for TYK2-JH2. Tyk2-IN-8 inhibits JAK1-JH1 with IC50 of 3.0 nM. Tyk2-IN-8 can be used for the research of autoimmune disease[1].
Hedgehog IN-5 is an orally active small molecule inhibitor of the hedgehog pathway. Hedgehog IN-5 can be used for the research of fibrotic disease[1].
GSK-3β inhibitor 9 (Compound 9b) is a highly selective, orally bioavailable and potent GSK-3β inhibitor with the IC50 of 35 nM. GSK-3β inhibitor 9 shows good pharmacokinetic profiles including favorable BBB penetration. GSK-3β inhibitor 9 can be used for the research of Alzheimer’s disease[1].
FLI-06 is an inhibitor of Notch signaling with an EC50 of 2.3 μM.
GSK-3 Inhibitor XIII is a potent and ATP-competitive GSK-3 inhibitor with a Ki of 24 nM[1][1][2].
CCT 365623 (CCT365623) hydrochloride is a potent, orally active small molecule inhibitor of lysyl oxidase (LOX) with IC50 of 0.89 uM; inhibits LOX actvity in living cell system (MDCK cysts) at 5 uM, reduces EGFR retention at the cell surface, suppresses EGFR and AKT phosphorylation driven by EGF, also activates SMAD2 and downregulates MATN2; delays the growth of primary and metastatic tumour cells in vivo.
Chrysomycin A (Chr-A), an antibiotic, can be obtained from Streptomyces. Chrysomycin A exhibits antitumor and anti-tuberculous and MRSA activities. As for glioblastoma, Chrysomycin A inhibits the proliferation, migration, and invasion of cancer cells through the Akt/GSK-3β/β-catenin signaling pathway[1].
(R,R)-VVD-118313 is the isomer of VVD-118313 (HY-151385). VVD-118313 is a selective JAK1 inhibitor and blocks JAK1-dependent trans-phosphorylation and cytokine signaling. VVD-118313 can be used for research of cancer[1].
SAG (hydrochloride) is a potent Smo receptor agonist, and activates the Hedgehog signaling pathway, with a Kd of 59 nM.