DW14383 is an irreversible pan-FGFR inhibitor that suppresses FGFR-dependent tumor growth in vitro and in vivo.

Fibroblast growth factor receptor (FGFR) is a promising anticancer target. Currently, most FGFR inhibitors lack sufficient selectivity and have nonnegligible activity against kinase insert domain receptor (KDR), limiting their feasibility due to the serious side effects. Notably, compensatory activation occurs among FGFR1-4, suggesting the urgent need to develop selective pan-FGFR1-4 inhibitors.

SAF-189s, a potent new-generation ROS1 inhibitor, is active against crizotinib-resistant ROS1 mutant-driven tumors.

The ROS1 fusion kinase is an attractive antitumor target. Though with significant clinical efficacy, the well-known first-generation ROS1 inhibitor (ROS1i) crizotinib inevitably developed acquired resistance due to secondary point mutations in the ROS1 kinase. Novel ROS1is effective against mutations conferring secondary crizotinib resistance, especially G2032R, are urgently needed.

Identification of mitoxantrone as a new inhibitor of ROS1 fusion protein in non-small cell lung cancer cells.

Mitoxantrone, an FDA-approved drug for multiple sclerosis and hormone refractory prostate cancer, is identified as a potent inhibitor of ROS1 fusion protein by screening in non-small cell lung cancer cells. Mitoxantrone can suppress the phosphorylation of ROS1 and subsequently inhibit its downstream signaling pathway and thus induce cell apoptosis.

Discovery of a new series of imidazo[1,2-a]pyridine compounds as selective c-Met inhibitors.

Aim: Aberrant c-Met activation plays a critical role in cancer formation, progression and dissemination, as well as in development of resistance to anticancer drugs. Therefore, c-Met has emerged as an attractive target for cancer therapy. The aim of this study was to develop new c-Met inhibitors and elaborate the structure-activity relationships of identified inhibitors.

SOMG-833, a novel selective c-MET inhibitor, blocks c-MET-dependent neoplastic effects and exerts antitumor activity.

The hepatocyte growth factor/c-MET signaling axis plays an important role in tumor cell proliferation, metastasis, and tumor angiogenesis, and therefore presents as an attractive target for cancer therapy. Notably, most small-molecule c-MET inhibitors currently undergoing clinical trials are multitarget inhibitors with the unwanted inhibition of additional kinases, often accounting for undesirable toxicity. Here, we discovered SOMG-833 [3-(4-methylpiperazin-1-yl)-5-(3-nitrobenzylamino)-7-(trifluoromethyl) quinoline] as a potent and selective small-molecule c-MET inhibitor, with an average IC50 of 0.

Novel 5-(benzyloxy)pyridin-2(1H)-one derivatives as potent c-Met inhibitors.

A series of novel 5-(benzyloxy)pyridin-2(1H)-ones were designed, synthesized and biologically evaluated for c-Met inhibition. Various amides and benzoimidazoles at C-3 position were investigated. A potent compound 12b with a c-Met IC50 of 12nM was identified.

Trigoxyphins A-G: diterpenes from Trigonostemon xyphophylloides.

Six new oxygenated daphnane-type diterpenoids, trigoxyphins A-F (1-6), a phenanthrene-type diterpenoid, trigoxyphin G (7), and two known compounds were isolated from twigs of Trigonostemon xyphophylloides. Their structures were established using spectroscopic methods. Compounds 1 and 2 exhibited strong cytotoxic activity against HL60 (IC(50): 0.

Cucumber mosaic virus 2b protein inhibits RNA silencing pathways in green alga Chlamydomonas reinhardtii.

The functions of RNA silencing are repression of endogenous gene expression and antiviral defense in plants and animals. Cucumber mosaic virus 2b (CMV2b) is a suppressor of RNA silencing in higher plants. In the present study, we evaluated the RNA silencing suppressor activity of CMV2b in Chlamydomonas reinhardtii.

Sesquiterpenes and dimeric sesquiterpenoids from Sarcandra glabra.

Two new sesquiterpenes, sarcandralactones A (1) and B (2), and five new dimeric sesquiterpenoids, sarcandrolides A-E (3-7), along with 10 known compounds were isolated from the whole plants of Sarcandra glabra. Their structures were elucidated on the basis of spectroscopic analysis. Some of the new isolates exhibit significant cytotoxicities when tested against a small panel of tumor cell lines.

Proteomic analysis of curdlan-producing Agrobacterium sp. in response to pH downshift.

During batch cultivation of Agrobacterium sp. ATCC 31750, proteome analysis in response to a pH downshift from 7.0 to 5.