BIIB-024, also known as MLN2480, and AMG 2112819, is an oral, selective pan-Raf kinase inhibitor. The Raf kinases (A-Raf, B-Raf and C-Raf) are key regulators of cell proliferation and survival within the mitogen-activated protein kinase (MAPK) pathway. The MAPK pathway is frequently disregulated in human cancers, often via activating mutations of Ras or Raf. BIIB-024 inhibits MAPK pathway signaling in BRAF mutant and some RAS mutant preclinical cancer models at concentrations that are tolerated in vivo. BIIB-024 is most potent in BRAF mutant melanoma models but also has single agent activity in some RAS mutant models. The combination of BIIB-024 with TAK-733 inhibits the growth of a broader range of RAS mutant tumor models than single agent BIIB-024, including primary human tumor xenograft models of melanoma and CRC. BIIB-024 is in phase I clinical trials for the treatment of malignant melanoma and solid tumours.

Pazopanib (VOTRIENT) is an orally bioavailable multi-targeted tyrosine kinase receptor inhibitor. Pazopanib inhibits vascular endothelial growth factor receptor (VEGFR)-1, VEGFR-2, VEGFR-3, platelet-derived growth factor receptor (PDGFR)-α and -β, fibroblast growth factor receptor (FGFR) -1 and -3, cytokine receptor (Kit), interleukin-2 receptor inducible T-cell kinase (Itk), leukocyte-specific protein tyrosine kinase (Lck), and transmembrane glycoprotein receptor tyrosine kinase (c-Fms). In an vitro study, pazopanib exerted anti-tumor effect through mechanisms including the Raf-MAPK/ERK (MEK)-extracellular signal-regulated kinase (ERK) pathway. It has good oral exposure and inhibits angiogenesis and tumor growth in mice. Pazopanib (VOTRIENT) was developed by GlaxoSmithKline for the treatment of solid tumours and age-related macular degeneration. However, Novartis acquired all the rights to the drug from GlaxoSmithKline. Pazopanib (VOTRIENT) is indicated for the treatment of patients with advanced renal cell carcinoma and advanced soft tissue sarcoma.

A- 770041 is a src-family selective lck inhibitor with greater than 90% inhibition of IL-2 in vivo at 8 h when dosed at ED90 in mice and rats. A-770041 is greater than 300-fold selective against fyn, the other src-family kinase involved in T-cell signaling. A-770041 exhibits >60-fold selectivity versus the src-family members src and fgr, and >8-fold versus lyn and hck. Selectivity against the receptor tyrosine kinases tie-2 and kdr was >340-fold. In the anti-CD3 stimulated human whole blood assay, A-770041 inhibited IL-2 production with an IC50 of 0.08 uM. In rats, a correlation of concanavalin A-induced serum IL-2 levels to A-770041 concentrations was observed. Inhibition of IL-2 production was shown to be dependent upon in vivo plasma concentration of A-770041 with an in vivo EC50 of 0.078 uM. A-770041 represents the most selective lck inhibitor described to date and represents an advance not only in the understanding of structural features important for src-family selectivity, but also in the potential arsenal for the treatment of immunological conditions, in particular transplant rejection.

LDC1267 preferentially inhibits TAM tyrosine kinase receptors Tyro3, Axl and Mer at low nanomolarity. LDC1267 conferred therapeutic potential, efficiently enhancing anti-metastatic natural killer (NK) cells activity. In vivo the compound markedly reduced murine mammary cancer and melanoma metastases dependent on NK cells.

Lavendustin C or HDBA (2-hyroxyl-5-(2,5-dihydroxybenzylamino) benzoic acid) is the active pharmacophore of lavendustin A, a tyrosine kinase inhibitor isolated from a butyl acetate extract of Streptomyces griseolavendus.

Piceatannol (3,3′,4,5′-tetrahydroxy-trans-stilbene; PIC) is a naturally occurring stilbene present in diverse plant sources. Piceatannol is a hydroxylated analog of resveratrol and produced from resveratrol by microsomal cytochrome P450 1A11/2 and 1B1 activities. Like resveratrol, Piceatannol has a broad spectrum of health beneficial effects, many of which are attributable to its antioxidative and anti-inflammatory activities. Piceatannol exerts anticarcinogenic effects by targeting specific proteins involved in regulating cancer cell proliferation, survival/death, invasion, metastasis, angiogenesis, etc. in the tumor microenvironment. Piceatannol also has other health promoting and disease preventing functions, such as anti-obese, antidiabetic, neuroprotective, cardioprotective, anti-allergic, anti-aging properties. A comprehensive review of PIC concludes that the compound has the health promoting and disease preventive potential. However, low water-solubility and bioavailability of PIC limit its pharmaceutical application and also use in functional foods. In this context, it is noticeable that beta-cyclodextrin was found to improve the bioavailability, the solubility and the stability of Piceatannol.