Bcl-2, encoded in humans by the BCL2 gene, is the founding member of the Bcl-2 family of regulator proteins. BCL2 blocks programmed cell death (apoptosis) while other BCL2 family members can either inhibit or induce it. It was the first apoptosis regulator identified in any organism.
Wortmannin, a steroid metabolite of the fungi Penicillium funiculosum, Talaromyces wortmannii, is a non-specific, covalent inhibitor of phosphoinositide 3-kinases (PI3Ks). It has an in vitro inhibitory concentration (IC50) of around 5 nM, making it a more potent inhibitor than LY294002, another commonly used PI3K inhibitor. It displays a similar potency in vitro for the class I, II, and III PI3K members although it can also inhibit other PI3K-related enzymes such as mTOR, DNA-PKcs, some phosphatidylinositol 4-kinases, myosin light chain kinase (MLCK) and mitogen-activated protein kinase (MAPK) at high concentrations Wortmannin has also been reported to inhibit members of the polo-like kinase family with IC50 in the same range as for PI3K. The half-life of wortmannin in tissue culture is about 10 minutes due to the presence of the highly reactive C20 carbon that is also responsible for its ability to covalently inactivate PI3K. Wortmannin is a commonly used cell biology reagent that has been used previously in research to inhibit DNA repair, receptor-mediated endocytosis and cell proliferation.
Targeted therapy or molecularly targeted therapy is one of the major modalities of medical treatment (pharmacotherapy) for cancer, others being hormonal therapy and cytotoxic chemotherapy. As a form of molecular medicine, targeted therapy blocks the growth of cancer cells by interfering with specific targeted molecules needed for carcinogenesis and tumor growth, rather than by simply interfering with all rapidly dividing cells. Because most agents for targeted therapy are biopharmaceuticals, the term biologic therapy is sometimes synonymous with targeted therapy when used in the context of cancer therapy. However, the modalities can be combined; antibody-drug conjugates combine biologic and cytotoxic mechanisms into one targeted therapy.
Cediranib is a potent inhibitor of vascular endothelial growth factor (VEGF) receptor tyrosine kinases.
Mocetinostat (MGCD0103) is a benzamide histone deacetylase inhibitor undergoing clinical trials for treatment of various cancers including follicular lymphoma, Hodgkin's lymphoma and acute myelogenous leukemia.
Phosphoinositide 3-kinase inhibitors are a class of medical drugs that are mainly used to treat advanced cancers. They function by inhibiting one or more of the phosphoinositide 3-kinase (PI3K) enzymes, which are part of the PI3K/AKT/mTOR pathway. This signal pathway regulates cellular functions such as growth and survival. It is strictly regulated in healthy cells, but is always active in many cancer cells, allowing the cancer cells to better survive and multiply. PI3K inhibitors block the PI3K/AKT/mTOR pathway and thus slow down cancer growth. They are examples of a targeted therapy. While PI3K inhibitors are an effective treatment, they can have very severe side effects and are therefore only used if other treatments have failed or are not suitable.
A CDK inhibitor is any chemical that inhibits the function of CDKs. They are used to treat cancers by preventing overproliferation of cancer cells. The US FDA approved the first drug of this type, palbociclib (Ibrance), a CDK4/6 inhibitor, in February 2015, for use in postmenopausal women with breast cancer that is estrogen receptor positive and HER2 negative. While there are multiple cyclin/CDK complexes regulating the cell cycle, CDK inhibitors targeting CDK4/6 have been the most successful; four CDK4/6 inhibitors have been FDA approved. No inhibitors targeting other CDKs have been FDA approved, but several compounds are in clinical trials.
Crizotinib, sold under the brand name Xalkori among others, is an anti-cancer medication used for the treatment of non-small cell lung carcinoma (NSCLC). Crizotinib inhibits the c-Met/Hepatocyte growth factor receptor (HGFR) tyrosine kinase, which is involved in the oncogenesis of a number of other histological forms of malignant neoplasms. It also acts as an ALK and ROS1 inhibitor.
Dactolisib is an imidazoquinoline derivative acting as a PI3K inhibitor. It also inhibits mTOR. It is being investigated as a possible cancer treatment.
Gene expression profiling has revealed that diffuse large B-cell lymphoma (DLBCL) is composed of at least 3 different sub-groups, each having distinct oncogenic mechanisms that respond to therapies in different ways. Germinal Center B-Cell like (GCB) DLBCLs appear to arise from normal germinal center B cells, while Activated B-cell like (ABC) DLBCLs are thought to arise from postgerminal center B cells that are arrested during plasmacytic differentiation. The differences in gene expression between GCB DLBCL and ABC DLBCL are as vast as the differences between distinct types of leukemia, but these conditions have historically been grouped together and treated as the same disease.
Temozolomide, sold under the brand name Temodar among others, is an anticancer medication used to treat brain tumors such as glioblastoma and anaplastic astrocytoma. It is taken by mouth or via intravenous infusion.
Volasertib is an experimental small molecule inhibitor of the PLK1 protein being developed by Boehringer Ingelheim for use as an anti-cancer agent. Volasertib is the second in a novel class of drugs called dihydropteridinone derivatives.
Angiokinase inhibitors are a new therapeutic target for the management of cancer. They inhibit tumour angiogenesis, one of the key processes leading to invasion and metastasis of solid tumours, by targeting receptor tyrosine kinases. Examples include nintedanib, afatinib and motesanib.
Abexinostat is an experimental drug candidate for cancer treatment. It was developed by Pharmacyclics and licensed to Xynomic. As of 2013, it was in Phase II clinical trials for B-cell lymphoma. Pre-clinical study suggests the potential for treatment of different types of cancer as well.
BMS-906024 is a drug with a benzodiazepine structure, developed by Bristol-Myers Squibb and disclosed at the spring 2013 American Chemical Society meeting in New Orleans to treat breast, lung, colon cancers and leukemia. The drug works as a pan-Notch inhibitor. The structure is one of a set patented in 2012, and is being studied in clinical trials.
Dinaciclib (SCH-727965) is an experimental drug that inhibits cyclin-dependent kinases (CDKs). It is being evaluated in clinical trials for various cancer indications.
Resminostat is an orally bioavailable inhibitor of histone deacetylases (HDACs), of which inhibitors are antineoplastic agents.
GL-ONC1 is an investigational therapeutic product consisting of the clinical grade formulation of the laboratory strain GLV-1h68, an oncolytic virus developed by Genelux Corporation. GL-ONC1 is currently under evaluation in Phase I/II human clinical trials in the United States and Europe.
Abemaciclib, sold under the brand name Verzenio among others, is a medication for the treatment of advanced or metastatic breast cancers. It was developed by Eli Lilly and it acts as a CDK inhibitor selective for CDK4 and CDK6.
ABT-737 is a small molecule drug that inhibits Bcl-2 and Bcl-xL, two members of the Bcl-2 family of evolutionarily-conserved proteins that share Bcl-2 Homology (BH) domains. First developed as a potential cancer chemotherapy, it was subsequently identified as a senolytic.
