D4476 is a potent, selective and cell-permeable inhibitor of casein kinase 1(CK1) with an IC50 value of 0.3 μM in vitro.
Sedanolide, a natural compound occurring in edible umbelliferous plants, possesses anti-inflammatory and antioxidant activities[1][2].
Afatinib (BIBW 2992) is an irreversible EGFR family inhibitor with IC50s of 0.5 nM, 0.4 nM, 10 nM and 14 nM for EGFRwt, EGFRL858R, EGFRL858R/T790M and HER2, respectively.
A novel lysosomotropic REV-ERB ligand that has a dual inhibitory activity toward REV-ERB-mediated transcriptional regulation and autophagy; relieves REV-ERB-mediated transcriptional repression, significantly increases autophagy-associated protein p62 in treated cells; disrupts lysosomal function, blocks the autophagy process at the late stage, and reduces cancer cell viability; a novel dual autophagy/REV-ERB inhibitor more cytotoxic than chloroquine.
Schisandrin has various therapeutic effects on a range of medical conditions such as anti-asthmatic, anti-cancer, and anti-inflammatory effects.IC50 value:Target:in vitro: Sch inhibited the pro-fibrotic activity of TGF-β1 in AML12 cells; thus, it suppressed the accumulation of ECM proteins. Also, Sch inhibited the EMT as assessed by reduced expression of vimentin and fibronectin, and increased E-cadherin and ZO-1 in TGF-β1 induced AML12 cells. Sch reduced TGF-β1-mediated phosphorylation of Smad2/3 and Smad3/4 DNA binding activity. On the other hand, Sch reduced TGF-β1-induced ERK1/2 and PI3K/Akt phosphorylation in the non-Smad pathway [1]. the anti-inflammatory properties of schisandrin result from the inhibition of nitric oxide (NO) production, prostaglandin E(2) (PGE(2)) release, cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression, which in turn results from the inhibition of nuclear factor-kappaB (NF-kappaB), c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) activities in a RAW 264.7 macrophage cell line [2].
Irinotecan-d10 ((+)-Irinotecan-d10) is a deuterium labeled Irinotecan ((+)-Irinotecan). Irinotecan ((+)-Irinotecan) is a topoisomerase I inhibitor, preventing religation of the DNA strand by binding to topoisomerase I-DNA complex[1].
Arctigenin is a lignan found in certain plants of the Asteraceae; it has shown antiviral and anticancer effects in glass; it is the aglycone of arctiin.IC50 value: Target: anticancer agentArctiin and its aglucone, arctigenin from the fruits of Arctium lappa L. showed potent in vitro antiviral activities against influenza A virus (A/NWS/33, H1N1) (IFV). Based on the data from time-of-addition experiments and on release tests of progeny viruses, arctigenin was assumed to interfere with early event(s) of viral replication after viral penetration into cells, and to suppress the release of progeny viruses from the host cells [1]. arctigenin treatment reduced viability of bladder cancer T24 cells in a dose- and time-dependent manner after treatment with arctigenin (10, 20, 40, 80, and 100 μmol/L) for 24 hr and 48 hr. Arctigenin treatment clearly arrested tumor cells in the G1 phase of the cell cycle. At the molecular level, arctigenin treatment decreased cyclin D1 expression, whereas CDK4 and CDK6 expression levels were unaffected. Moreover, arctigenin selectively altered the phosphorylation of members of the MAPK superfamily, decreasing phosphorylation of ERK1/2 and activated phosphorylation of p38 significantly in a dose-dependent manner [2]. The use of arctigenin has been shown to be effective in a mouse model of Japanese encephalitis [3].
Troglitazone-d4 is deuterium labeled Troglitazone. Troglitazone is a PPARγ agonist, with EC50s of 550 nM and 780 nM for human and murine PPARγ receptor, respectively.
Ixazomib (MLN2238) is a selective, potent, and reversible proteasome inhibitor, which inhibits the chymotrypsin-like proteolytic (β5) site of the 20S proteasome with an IC50 of 3.4 nM (Ki of 0.93 nM).
Sotetsuflavone is a potent inhibitor of DENV-NS5 RdRp (Dengue virus NS5 RNA-dependent RNA polymerase) with an IC50 of 0.16 uM, is the most active compound of this series .
Brefeldin A is a specific inhibitor of protein trafficking which blocks the protein transport from the endoplasmic reticulum to the Golgi complex.
Naringin is a major flavanone glycoside obtained from tomatoes, grapefruits, and many other citrus fruits. Naringin exhibits biological properties such as antioxidant, anti-inflammatory, and antiapoptotic activities.
Beclin1-ATG14L interaction inhibitor 1 (com 19) is a selective Beclin1-ATG14L interaction inhibitor. This protein interaction mechanism specifically targets complex I of the lipid kinase VPS34 without affecting complex II. Because the integrity of VPS34 complex II depends on the Beclin 1-UVRAG interaction. Beclin1-ATG14L interaction inhibitor 1 can disrupt the formation of VPS34 complex I and inhibit autophagy, but does not affect complex II-related vesicle transport[1].
4-Hydroxytolbutamide (Hydroxytolbutamide) is a metabolite of Tolbutamide. 4-Hydroxytolbutamide is metabolized by CYP2C8 and CYP2C9. Tolbutamide is a first generation potassium channel blocker and a sulfonylurea oral antidiabetic[1][2].
Silibinin, an effective anti-cancer and chemopreventive agent, has been shown to exert multiple effects on cancer cells, including inhibition of both cell proliferation and migration.IC50 value:Target: anticancerin vitro: silibinin significantly induced the expression of the non-steroidal anti-inflammatory drug-activated gene-1 (NAG-1) in both p53 wild-type and p53-null cancer cell lines, suggesting that silibinin-induced NAG-1 up-regulation is p53-independent manner.Silibinin up-regulates early growth response-1 (EGR-1) expression [1]. silibinin induced cell death in human breast cancer cell lines MCF7 and MDA-MB-231. Silibinininduced cell death was attenuated by antioxidants, N-acetylcysteine (NAC) and Trolox, suggesting that the effect of silibinin was dependent on generation of reactive oxygen species (ROS) [2]. SIL treatment resulted in a dose- and time-dependent inhibition of HCC cell viability, SIL exhibited strong antitumor activity, as evidenced not only by reductions in tumor cell adhesion, migration, intracellular glutathione (GSH) levels and total antioxidant capability (T-AOC) but also by increases in the apoptotic index, caspase3 activity, and reactive oxygen species (ROS). SIL treatment decreased the expression of the Notch1 intracellular domain (NICD), RBP-Jκ, and Hes1 proteins, upregulated the apoptosis pathway-related protein Bax, and downregulated Bcl2, survivin, and cyclin D1. Notch1 siRNA (in vitro) or DAPT (a known Notch1 inhibitor, in vivo) further enhanced the antitumor activity of SIL, and recombinant Jagged1 protein (a known Notch ligand in vitro) attenuated the antitumor activity of SIL [3].in vivo: Topical application of silibinin at the dose of 9 mg/mouse effectively suppressed oxidative stress and deregulated activation of inflammatory mediators and tumorigenesis[4]. The kidney cortex of vehicle-treated control OVE26 mice displayed greater Nox4 expression and twice as much superoxide production than cortex of silybin-treated mice. The glomeruli of control OVE26 mice displayed 35% podocyte drop out that was not present in the silybin-treated mice [5].
Doxorubicin hydrochloride is a cytotoxic anthracycline antibiotic for the treatment of multiple cancers. The possible mechanisms by which doxorubicin acts in the cancer cell are intercalation into DNA and disruption of topoisomerase-II-mediated DNA repair.
SRT 1720 Hydrochloride is a selective activator of SIRT1 with an EC1.5 of 0.16 μM, and shows less potent activities on SIRT2 and SIRT3 with EC1.5s of 37 μM and 300 μM, respectively.
MTX115325 (Example 1) is an orally active, brain-penetrating USP30 inhibitor (IC50=12 nM) with neuroprotective activity. MTX115325 increases ubiquitination (EC50=32 nM) of the mitochondrial outer membrane protein TOM20 (a USP30 substrate), increasing mitophagy. MTX115325 prevents dopaminergic neuron loss and preserves striatal dopamine[1].
Nocodazole is a rapidly-reversible inhibitor of microtubule. Nocodazole binds to β-tubulin and disrupts microtubule assembly/disassembly dynamics, which prevents mitosis and induces apoptosis in tumor cells.
Salicylic acid inhibits cyclo-oxygenase-2 (COX-2) activity independently of transcription factor (NF-κB) activation.
AC-73 is a first specific, orally active inhibitor of cluster of differentiation 147 (CD147), which specifically disrupts CD147 dimerization, thereby mainly suppressing the CD147/ERK1/2/STAT3/MMP-2 pathways. AC-73 inhibits the motility and invasion of hepatocellular carcinoma cells[1]. AC-73 is also an anti-proliferative drug and an inducer of autophagy in leukemic cells[2].
SMER28 is an autophagy activator acting via an mTOR-independent mechanism. SMER28 prevents the accumulation of amyloid beta peptide.
Sulindac is a non-steroidal antiinflammatory agent, acts as a COX-2 inhibitor, and inhibits overexpression of COX-2.
Linifanib (ABT-869) is a multi-targeted inhibitor of VEGF and PDGFR receptor family with IC50s of 3, 4, 66, 4 nM for KDR, Flt-1, PDGFRβ and FLT3, respectively.
Liensinine is an autophagy/mitophagy inhibitor. Liensinine, a major isoquinoline alkaloid, extracted from the seed embryo of Nelumbo nucifera Gaertn, has a wide range of biological activities, including anti-arrhythmias, anti-hypertension, anti-pulmonary fibrosis, relaxation on vascular smooth muscle, etc[1].
Ketanserin tartrate is a selective 5-HT receptor antagonist. Ketanserin tartrate also blocks hERG current (IhERG) in a concentration-dependent manner (IC50=0.11 μM).
Rupatadine D4 fumarate (UR-12592 D4 fumarate) is a deuterium labeled Rupatadine fumarate. Rupatadine Fumarate (UR-12592 Fumarate) is a potent dual PAF/H1 antagonist with Ki of 0.55/0.1 μM(rabbit platelet membranes/guinea pig cerebellum membranes)[1][2][3].
VO-OHPic is a reversible, noncompetitive and selective PTEN inhibitor with an IC50 of 46 nM. VO-OHPic attenuates apoptosis, adverse cardiac remodeling, and pro-inflammatory M1 macrophages in doxorubicin-induced cardiomyopathy. VO-OHPic inhibits autophagy[1][2][3].
GSK4112 is a Rev-erbα agonist with EC50 of 0.4 μM, also is a small molecule chemical probe for the cell biology of the nuclear heme receptor Rev-erbα.IC50 value: 0.4 μM (EC50)Target: Rev-erbαin vitro: GSK4112 profiled as a Rev-erb agonist in cells to inhibit expression of the circadian target gene bmal1. In addition, GSK4112 repressed the expression of gluconeogenic genes in liver cells and reduced glucose output in primary hepatocytes. Therefore, GSK4112 is useful as a chemical tool to probe the function of Rev-erb in transcriptional repression, regulation of circadian biology, and metabolic pathways. Additionally, GSK4112 may serve as a starting point for design of Rev-erb chemical probes with in vivo pharmacologicalm activity.
NL-1 is a mitoNEET inhibitor with antileukemic effect. NL-1 inhibits REH and REH/Ara-C cells growth with IC50s of 47.35 µM and 56.26 µM, respectively. NL-1-mediated death in leukemic cells requires the activation of the autophagic pathway[1].