NVP-ADW742 is a novel small weight molecular inhibitor of insulin-like growth factor-1 receptor (IGF-IR), which is investigated for treatment of different types of cancers.

BAY-36-7620 is a potent and selective antagonist at mGlu1receptors and inhibits >60% of mGlu1a receptor constitutive activity (IC50 = 0.38 uM). BAY-36-7620 is thus the first described mGlu1 receptor inverse agonist. It impairs classical conditioning and associated synaptic plasticity in hippocampal neurons. BAY-36-7620 exhibits neuroprotective and anticonvulsive effects in vivo following systemic administration.

A novel pyrido[2,3-d]pyrimidine derivative, PD-180970, has been shown to potently inhibit Bcr-Abl and induce apoptosis in Bcr-Abl-expressing leukemic cells. PD-180970 is active against several Bcr-Abl mutations that are resistant to imatinib and support the notion that developing additional Abl kinase inhibitors would be useful as a treatment strategy for chronic myelogenous leukemia. PD-180970 is also an inhibitor of Src, and KIT.

Isoliquiritin is a flavonoid glycoside compound from licorice possessing a broad spectrum of pharmacological activities including antioxidant, anti-inflammatory, and anti-depression activities. It was shown that isoliquiritin has a cytoprotective effect on corticosterone-induced neurotoxicity in PC12 cells, which may be related to its antioxidant action, inhibition of [Ca2+]i overload, and inhibition of the mitochondrial apoptotic pathway. In addition, it was found that isoliquiritin inhibited the p53-dependent pathway and showed crosstalk between Akt activities. Thus isoliquiritin may be an alternative agent for the treatment of lung cancer.

PD 173074 is a potent ATP-competitive inhibitor of fibroblast growth factor receptor 1 and 3. PD173074 is also an effective inhibitor of FGFR2, FGFR4, and VEGFR2. Compared to FGFR1, PD173074 weakly inhibits the activities of Src, InsR, EGFR, PDGFR, MEK, and PKC with 1000-fold or greater IC50 values. PD173074 inhibits autophosphorylation of FGFR1 and VEGFR2 in a dose-dependent manner with IC50 of 1-5 nM and 100-200 nM, respectively. PD173074 specifically inhibits FGF-2-mediated effects on proliferation, differentiation, and MAPK activation in oligodendrocyte (OL) lineage cells. PD173074 treatment potently reduces the viability of FGFR3-expressing KMS11 and KMS18 cells. Inhibition of aFGF-stimulated MM cell growth by PD173074 is highly correlated with the expression of FGFR3. PD173074 treatment completely abolishes NIH 3T3 transformation mediated by Y373C FGFR3 but not by Ras V12, demonstrating that PD173074 specifically targets FGFR3-mediated cell transformation and lacks nonspecific cytotoxic effect. Administration of PD173074 at 1 mg/kg/day or 2 mg/kg/day in mice can effectively block angiogenesis induced by either FGF or VEGF in a dose-dependent manner with no apparent toxicity. PD173074 inhibits in vivo growth of mutant FGFR3-transfected NIH 3T3 cells in nude mice. Inhibition of FGFR3 by PD173074 delays tumor growth and increases survival of mice in a KMS11 xenograft myeloma model. In the H-510 xenograft, oral administration of PD173074 blocks tumor growth similar to that seen with single-agent cisplatin administration, increasing median survival compared with control sham-treated animals. In H-69 xenografts, PD173074 induces complete responses lasting >6 months in 50% of mice. These effects are correlated with increased apoptosis in excised tumors, but not a consequence of disrupted tumor vasculature. PD173074 seems to be discontinued in the preclinical development stage, and no clinical data are available currently.

Beauvericin is a famous mycotoxin produced by many fungi, such as Beaveria bassiana and Fusarium spp. Beauvericin is a cyclic hexadepsipeptide (Figure 1) that belongs to the enniatin antibiotic family. It contains three D-hydroxyisovaleryl and three N-methylphenylalanyl residues in an alternating sequence. Beauvericin was first isolated from Beaveria bassiana, which is a common and commercial entomopathogenic mycoinsecticide. Beauvericin was one of the active constituents of B. bassiana and was confirmed to have antimicrobial and anti-tumor activities. Beauvericin has a strong antibacterial activity against human, animal and plant pathogenic bacteria with no selectively between Gram-positive and Gram-negative bacteria. The cytotoxicity of beauvericin to human tumor cells has been frequently reported.

Coptisine (COP), a protoberberine alkaloid, is widely found in Chinese medicinal plants (family Berberidaceae, Ranunculaceae and Papaveraceae). It is reported that COP has a wide range of pharmacological and biological activities, including antibacterial, hypoglycemic, anti-tumorigenic, and gastric-mucous membrane protection. Considerable attention has been focused on its activity against central nervous system disorders, such as improving the symptoms of Alzheimer’s disease and even preventing its onset, by exerting antidepressant effects as a potent type A monoamine oxidase inhibitor. Coptisine was found to be an efficient uncompetitive Indoleamine 2,3-dioxygenase inhibitor. Coptisine is a potent inhibitor of human organic cation transporters.

AG1478 (also known as Tyrphostin AG 1478 ) is a selective EGFR inhibitor, which induced cell cycle arrest in G1 phase, is developed as potential drug for nasopharyngeal carcinoma treatment. In addition was shown, that AG1478 effectively blocked the leiomyoma cell growth and is unaffected by the presence of physiological concentrations of progesterone and estradiol. The growth-arresting properties of AG1478, unaffected by ovarian steroidal hormones, identify it as a potential lead agent for the non-surgical management of uterine leiomyomas. Also was investigated the action of the combination AG1478 in combination with HGF tyrosine kinase inhibitors on non-small cell lung cancer (NSCLC) cells, and was suggested, that these combinations of drugs could be potentially used for treatment of NSCLC.

Aucubin is found in common verbena. Aucubin is a monoterpenoid based compound. Aucubin, like all iridoids, has a cyclopentan-[C]-pyran skeleton. Aucubin is found in the leaves of Aucuba japonica (Cornaceae), Eucommia ulmoides (Eucommiaceae), and Plantago asiatic (Plantaginaceae), etc, plants used in traditional Chinese and folk medicine. Aucubin was found to protect against liver damage induced by carbon tetrachloride or alpha-amanitin in mice and rats when 80 mg/kg was dosed intraperitoneally. Aucubin has been shown to exhibit anti-proliferative and apoptotic functions. Aucubin has shown effectiveness as antifungal and suggests its promising potential use as solution for C. albicans biofilm-related infections. Aucubin has a range of biological activities, including anti-inflammatory, anti-microbial, anti-algesic as well as anti-tumor activities.

The ALOIN A (barbaloin) is considered to be the most specific secondary phytoconstituent in Aloe species, widely distributed throughout the world. Barbaloin has been found to have a strong inhibitory effect on histamine release from mast cells. Orally administered barbaloin is poorly absorbed but is metabolized by intestinal microflora to aloe emodin, which is readily absorbed. Barbaloin is the main medicinal constituent of aloe vera, which has anti-inflammatory activity. Moreover, it has strong anti-oxidant and anti-tumor properties. For example, barbaloin inhibited the proliferation and metastasis of non-small cell lung carcinoma cells in vivo and in vitro. Barbaloin demonstrated a cardioprotective potential: barbaloin pretreatment attenuates myocardial ischemia-reperfusion injury. Plus, it might be used as an antiarrhythmic drug.