Manzamine A, an orally active beta-carboline alkaloid, inhibits specifically GSK-3β and CDK-5 with IC50s of 10.2 μM and 1.5 μM, respectively. Manzamine A targets vacuolar ATPases and inhibits Autophagy in pancreatic cancer cells. Manzamine A has antimalarial and anticancer activities. Manzamine A also shows potent activity against HSV-1[1][2][3][4].
LX2343 is a BACE1 enzyme inhibitor with an IC50 value of 11.43±0.36 μM. LX2343 acts as a non-ATP competitive PI3K inhibitor with an IC50 of 15.99±3.23 μM. LX2343 stimulates autophagy in its promotion of Aβ clearance.
Vps34-IN-4 (compound 19) is a potent, selective, and orally active inhibitor of VPS34. Vps34-IN-4 inhibits the autophagy in vivo. Autophagy is a dynamic process that regulates lysosomal-dependent degradation of cellular components[1].
Sunitinib (SU 11248) is a multi-targeted receptor tyrosine kinase inhibitor with IC50s of 80 nM and 2 nM for VEGFR2 and PDGFRβ, respectively.
Ruxolitinib S enantiomer is the S-enantiomer of Ruxolitinib. Ruxolitinib is the first potent, selective JAK1/2 inhibitor to enter the clinic with IC50 of 3.3 nM/2.8 nM in cell-free assays.
Cytochalasin E, an epoxide containing Aspergillus-derived fungal metabolite, inhibits angiogenesis and tumor growth. Cytochalasin E is a potent actin depolymerization agent, and it binds and caps the barbed end of actin filaments to prevent actin elongation[1][2].
Torkinib (PP 242) is a selective and ATP-competitive mTOR inhibitor with an IC50 of 8 nM. PP242 inhibits both mTORC1 and mTORC2 with IC50s of 30 nM and 58 nM, respectively.
Sodium Salicylate inhibits cyclo-oxygenase-2 (COX-2) activity independently of transcription factor (NF-κB) activation.
Crenolanib is a potent and selective inhibitor of wild-type and mutant isoforms of the class III receptor tyrosine kinases FLT3 and PDGFRα/β with Kds of 2.1 nM/3.2 nM, 0.74 nM, respectively.
Kaempferol inhibits estrogen receptor α expression in breast cancer cells and induces apoptosis in glioblastoma cells and lung cancer cells by activation of MEK-MAPK.
D4476 is a potent, selective and cell-permeable inhibitor of casein kinase 1(CK1) with an IC50 value of 0.3 μM in vitro.
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].
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).
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].
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.
Sulindac is a non-steroidal antiinflammatory agent, acts as a COX-2 inhibitor, and inhibits overexpression of COX-2.
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].
Betulinic acid is a natural pentacyclic triterpenoid, acts as a eukaryotic topoisomerase I inhibitor, with an IC50 of 5 μM, and possesses anti-HIV, anti-malarial, anti-inflammatory and anti-tumor properties.
Thioridazine, an antagonist of the dopamine receptor D2 family proteins, exhibits potent anti-psychotic and anti-anxiety activities. Thioridazine is also a potent inhibitor of PI3K-Akt-mTOR signaling pathways with anti-angiogenic effect. Thioridazine shows antiproliferative and apoptosis induction effects in various types of cancer cells, with specificity on targeting cancer stem cells (CSCs)[1][2][3][4].
Butein, a plant polyphenol isolated from Rhus verniciflua, inhibit the activation of protein tyrosine kinase and EGFR. target: EGFR [1]In vitro: 1) Butein inhibited the activation of AKT, extracellular signal-regulated kinase (ERKs) and p38 kinases in the presence of cisplatin.[2] 2) FoxO3a and its downstream molecules play a role in the synergistic effects of butein and cisplatin.[2]3) Butein suppresses cell proliferation and enhances apoptosis in paclitaxel-resistant ovarian cancer cells.[3]4) Butein activates FOXO3a/p27kip1 pathway in ALL cell lines.[4]5) Butein inhibited not only the epidermal growth factor (EGF)-stimulated auto-phosphotyrosine level of EGF receptor in HepG2 cells but also tyrosine-specific protein kinase activities of EGF receptor (IC50= 65 μM) and p60c-src(IC50= 65 μM)In vivo: 1) Butein in combination with cisplatin suppresses tumor growth and increases FoxO3a expression.[1]
Metformin D6 hydrochloride is a deuterium labeled Metformin hydrochloride. Metformin hydrochloride inhibits the mitochondrial respiratory chain in the liver, leading to activation of AMPK, enhancing insulin sensitivity for type 2 diabetes research. Metformin hydrochloride triggers autophagy[1].
Alisertib (MLN 8237) is a selective Aurora A inhibitor with an IC50 of 1.2 nM.
Sophocarpine is one of the significant alkaloid extracted from the traditional herb medicine Sophora flavescens which has many pharmacological properties such as anti-virus, anti-tumor, anti-inflammatory. Sophocarpine significantly inhibits the growth of gastric cancer (GC) cells through multiple mechanisms such as induction of autophagy, activation of cell apoptosis and down-regulation of cell survival PI3K/AKT signaling pathway. Sophocarpine has been demonstrated to have anti-tumor activity in various cancer cells, including hepatocellular carcinoma, prostate cancer and colorectal cancer[1].
Luteolin is a falconoid compound, which exhibits anticancer properties.IC50 value:Target: A natural for anticancer.In vitro: Luteolin exerted an anticancer effect against NCI-H460 cells through Sirt1-mediated apoptosis and the inhibition of cell migration [1]. The treatment of luteolin upregulated the expression levels of transforming growth factor β1 (TGF-β1), p21WAF1/CIP1, p27KIP1, Smad4, and Fas in HCC cells. Luteolin induced apoptotic cell death in Hep3B cells while caused G1 arrest in HepG2 cells. And it induces apoptosis from G1 arrest via three signaling pathways of TGF-β1, p53, and Fas/Fas-ligand in HCC cells [2].In vivo: The study of the effect of Luteolin on the improvement of cancerous cachexia in model mice showed that luteolin can improve the symptoms of cancer cachexia model mice.The mechanism may be related to inhibition of proteasome and calcium activated protease activity and lower the levels of cytokines [3].
Tizoxanide is the active metabolite of Nitazoxanide, which is a thiazolide anti-infective compound against anaerobic bacteria, protozoa, and a range of viruses.IC50 value: Target: Antiviral agentin vitro: Tizoxanide inhibited virus replication of all CIVs with 50% and 90% inhibitory concentrations ranging from 0.17 to 0.21 μM and from 0.60 to 0.76 μM, respectively [2]. Nitazoxanide and its primary metabolite, tizoxanide, inhibit hepatitis C virus (HCV) replication in HCV replicon systems. Interestingly, serial passage in nitazoxanide or tizoxanide resulted in increased sensitivity to alpha interferon 2b: EC(50)s and EC(90)s were reduced three- and eightfold, respectively [3].
PHY34 is a potent autophagy inhibitor with cytotoxic effects by inhibiting autophagy at a late stage (MDA-MB-435 IC50=23 nM, MDA-MB-231 IC50=5.2 nM); disrupts lysosomal function, significantly inhibits the growth of cancer cell lines in hollow fibers, as well as reduces ovarian tumor burden in a xenograft model.
SB 203580 hydrochloride is a widely used p38 MAPK inhibitor with an IC50 of 0.3-0.5 μM. It shows more than 100-fold selectivity over PKB, LCK, and GSK-3β.
Triclosan is an antibacterial and antifungal agent found in consumer products, including soaps, detergents, toys, and surgical cleaning treatments.
Gemcitabine hydrochloride is a DNA synthesis inhibitor with IC50s of 37.6, 42.9, 92.7, 89.3 and 131.4 nM in BxPC-3, Mia Paca-2, PANC-1, PL-45 and AsPC-1 cells, respectively.