CUR5g is a potent Autophagy inhibitor. CUR5g selectively inhibits autophagosome degradation in cancer cells by blocking autophagosome-lysosome fusion. CUR5g blocks the recruitment of STX17 to autophagosomes via a UVRAG-dependent mechanism, resulting in the inability of autophagosomes to fuse with lysosomes. CUR5g improves the anticancer effect of Cisplatin (HY-17394) against A549 cells both in vitro and in vivo[1].
Butyric acid is a histone deacetylase (HDAC) inhibitor, with anti-tumor effects in several cancers.
Glyphosate is an herbicidal derivative of the amino acid glycine. Glyphosate targets and blocks a plant metabolic pathway not found in animals, the shikimate pathway, required for the synthesis of aromatic amino acids in plants[1].
Rupatadine Fumarate (UR-12592 Fumarate) is a potent dual PAF/H1 antagonist with Ki of 0.55/0.1 uM(rabbit platelet membranes/guinea pig cerebellum membranes).IC50 value:Target: PAF/H1 antagonistin vitro: Rupatadine competitively inhibited histamine-induced guinea pig ileum contraction (pA2 = 9.29 +/- 0.06) without affecting contraction induced by ACh, serotonin or leukotriene D4 (LTD4). It also competitively inhibited PAF-induced platelet aggregation in washed rabbit platelets (WRP) (pA2 = 6.68 +/- 0.08) and in human platelet-rich plasma (HPRP) (IC50 = 0.68 microM), while not affecting ADP- or arachidonic acid-induced platelet aggregation [1]. The IC50 for rupatadine in A23187, concanavalin A and anti-IgE induced histamine release was 0.7+/-0.4 microM, 3.2+/-0.7 microM and 1.5+/-0.4 microM, respectively whereas for loratadine the IC50 was 2.1+/-0.9 microM, 4.0+/-1.3 M and 1.7+/-0.5 microM. SR-27417A exhibited no inhibitory effect [2].in vivo: Rupatadine blocked histamine- and PAF-induced effects in vivo, such as hypotension in rats (ID50 = 1.4 and 0.44 mg/kg i.v., respectively) and bronchoconstriction in guinea pigs (ID50 = 113 and 9.6 micrograms/kg i.v.). Moreover, it potently inhibited PAF-induced mortality in mice (ID50 = 0.31 and 3.0 mg/kg i.v. and p.o., respectively) and endotoxin-induced mortality in mice and rats (ID50 = 1.6 and 0.66 mg/kg i.v.) [1]. rupatadine treatment improved the declined lung function and significantly decreased animal death. Moreover, rupatadine was able not only to attenuate silica-induced silicosis but also to produce a superior therapeutic efficacy compared to pirfenidone, histamine H1 antagonist loratadine, or PAF antagonist CV-3988 [3].
SRT 1720 dihydrochloride is a selective and orally active activator of SIRT1 with an EC50 of 0.10 μM, and shows less potent activities on SIRT2 and SIRT3[1].
Imatinib is a tyrosine kinases inhibitor that inhibits c-Kit, Bcr-Abl, and PDGFR (IC50=100 nM) tyrosine kinases.
Imatinib Mesylate is a tyrosine kinases inhibitor that inhibits c-Kit, Bcr-Abl, and PDGFR (IC50=100 nM) tyrosine kinases.
Icaritin(Anhydroicaritin) is a component of Epimedium flavonoid isolated from Herba Epimedii; enhances osteoblastic differentiation of mesenchymal stem cells (MSCs) while it inhibits adipogenic differentiation of MSCs by inhibiting PPAR-g pathway.IC50 value:Target: in vitro: Icaritin was unable to promote proliferation, migration and tube like structure formation by human umbilical vein endothelial cells (HUVECs) in vitro [1]. Icaritin potently inhibited proliferation of K562 cells (IC50 was 8 μM) and primary CML cells (IC50 was 13.4 μM for CML-CP and 18 μM for CML-BC), induced CML cells apoptosis and promoted the erythroid differentiation of K562 cells with time-dependent manner. Furthermore, Icaritin was able to suppress the growth of primary CD34+ leukemia cells (CML) and Imatinib-resistant cells, and to induce apoptosis [2]. icaritin strongly inhibited the growth of breast cancer MDA-MB-453 and MCF7 cells. At concentrations of 2-3 μM, icaritin induced cell cycle arrest at the G(2)/M phase accompanied by a down-regulation of the expression levels of the G(2)/M regulatory proteins such as cyclinB, cdc2 and cdc25C. Icaritin at concentrations of 4-5 μM, however, induced apoptotic cell death characterized by the accumulation of the annexin V- and propidium iodide-positive cells, cleavage of poly ADP-ribose polymerase (PARP) and down-regulation of the Bcl-2 expression [3].in vivo: In mouse leukemia model, Icaritin could prolong lifespan of NOD-SCID nude mice inoculated with K562 cells as effective as Imatinib without suppression of bone marrow. Icaritin could up-regulate phospho-JNK or phospho-C-Jun and down-regulate phospho-ERK, phospho-P-38, Jak-2, phospho-Stat3 and phospho-Akt expression with dose- or time-dependent manner [2].
Lamotrigine(BW430C) is a novel anticonvulsant drug for inhibition of 5-HT and sodium channelTarget: Sodium ChannelLamotrigine stabilises presynaptic neuronal membranes by blockade of voltage-dependent sodium channels, thus preventing the release of excitatory neurotransmitters, particularly glutamate and aspartate [1]. In rat cerebral cortex tissue incubated with veratrine 10 mg/L, lamotrigine is twice as potent in inhibiting the release of glutamate and aspartate (ED 50 = 5.38 mg/L for each) than the release of GABA (ED50 = 11.2 mg/L), and is much less potent in inhibiting acetylcholine release (ED50 = 25.6 mg/L) when cortical slices is exposed to veratrine 75 mg/L. Basal glutamate release is unaffected [2]. Lamotrigine inhibits high-frequency sustained repetitive firing of sodium-dependent action potentials, indicating a direct effect on voltage-activated sodium channels [3]. Lamotrigine (Lamictal), a phenyltriazine derivative, is a well established anticonvulsant agent that has shown efficacy in the prevention of mood episodes in adult patients with bipolar I disorder. lamotrigine significantly delayed time to intervention for a depressive episode and showed limited efficacy in delaying time to intervention for a manic/hypomanic episode, compared with placebo. Lamotrigine is generally well tolerated [4].
MK-2206 free base is an orally active, highly potent and selective allosteric Akt inhibitor, with IC50s of 8, 12, and 65 nM for Akt1, Akt2, and Akt3, respectively. Many breast cancer cell lines, and PIK3CA-mutant and cell lines with PTEN loss are sensitive to MK-2206 free base. MK-2206 free base has anticancer activities[1][2].
U0126 is a potent and non-ATP competitive MEK1 and MEK2 inhibitor, with IC50s of 70 nM and 60 nM, respectively.
Glychionide A is a flavonoside that can be found in the roots of Glychirriza glabra. Glychionide A promotes apoptosis and autophagy of PANC-1 pancreatic cancer cells. Glychionide A can be used for the research of cancer[1][2].
Valproic acid is an HDAC inhibitor, with IC50 in the range of 0.5 and 2 mM, also inhibits HDAC1 (IC50, 400 μM), and induces proteasomal degradation of HDAC2; Valproic acid sodium salt is used in the treatment of epilepsy, bipolar disorder and prevention of migraine headaches.
Danusertib is a pyrrolo-pyrazole and aurora kinase inhibitor with IC50 of 13, 79, and 61 nM for Aurora A, B, and C, respectively.
MAO-B-IN-26 (Compound IC9) is a MAO-B and acetylcholinesterase inhibitor. MAO-B-IN-26 protects SH?SY5Y cells against Aβ induced cytotoxicity, morphological changes, ROS generation and membrane damage. MAO-B-IN-26 also inhibits Aβ induced autophagy and apoptosis. MAO-B-IN-26 can be used as a neuroprotective agent against Alzheimer’s disease[1].
Ponatinib is a potent, orally available multi-targeted kinase inhibitor with IC50s of 0.37 nM, 1.1 nM, 1.5 nM, 2.2 nM, and 5.4 nM for Abl, PDGFRα, VEGFR2, FGFR1, and Src, respectively.
Pregnenolone monosulfate acts as a signaling-specific inhibitor of cannabinoid CB1 receptor, reduces several effects of tetrahydrocannabinol (THC).
Meloxicam is a non-steroidal antiinflammatory agent, inhibits COX activity, with IC50s of 0.49 µM and 36.6 µM for COX-2 and COX-1, respectively.
Momelotinib (CYT387) is an ATP-competitive inhibitor of JAK1/JAK2 with IC50a of 11 nM and 18 nM,respectively. CYT387 shows much less activity against JAK3.
PTC-209 is a specific BMI-1 inhibitor with an IC50 of 0.5 μM.
Isorhapontigenin, an orally bioavailable dietary polyphenol isolated from the Chinese herb Gnetum cleistostachyum, displays anti-inflammatory effects. Isorhapontigenin induces autophagy and inhibits invasive bladder cancer formation[1][2].
Vemurafenib-d7 is deuterium labeled Vemurafenib. Vemurafenib (PLX4032) is a first-in-class, selective, potent inhibitor of B-RAF kinase, with IC50s of 31 and 48 nM for RAFV600E and c-RAF-1, respectively[1][4]. Vemurafenib induces cell autophagy[5].
α-Thujone is a monoterpene isolated from Thuja occidentalis essential oil with potent anti-tumor activities. α-Thujone is a reversible modulator of the GABA type A receptor and the IC50 for α-Thujone is 21 μM in suppressing the GABA-induced currents. α-Thujone induces ROS accumulation-dependent cytotoxicity, also induces cell apoptosis and autophagy. α-Thujone has antinociceptive, insecticidal, and anthelmintic activity, and easily penetrates the blood-brain barrier[1][2][3].
Vandetanib is a potent inhibitor of VEGFR2 with an IC50 of 40 nM.
Meloxicam sodium is a non-steroidal anti-inflammatory agent, inhibits COX activity, with IC50s of 0.49 µM and 36.6 µM for COX-2 and COX-1, respectively[1].
Maprotiline is a highly selective noradrenergic reuptake blocker, has strong antidepressant efficacy. Maprotiline induces cancer cells apoptosis by targeting ERK signaling pathway and CRABP1. Maprotiline restrains cell proliferation and metastasis, exhibits anticancer effect[1][2].
PD0325901 is a selective and cell permeable MEK inhibitor with an IC50 of 0.33 nM.
Sertaconazole (FI7056 free base) is a broad-spectrum topical antifungal agent, exhibits anti-inflammatory activity via activation of a p38-COX-2-PGE2 pathway. Sertaconazole is also a microtubule inhibitor, shows antiproliferative effect, induces apoptosis and autophagy, and can also inhibit the migration of cells[1][2][3][4].
Idelalisib (CAL-101) is a highly selective and potent p110δ inhibitor with an IC50 of 2.5 nM, showing 40- to 300-fold selectivity for p110δ over other PI3K class I enzymes.