PD-0325901 is an orally bioavailable inhibitor of mitogen-activated protein kinase kinases (MAPK/ERK kinases or MEK) with potential antineoplastic activity. MEK inhibitor PD325901, a derivative of MEK inhibitor CI-1040, selectively binds to and inhibits MEK, which may result in the inhibition of the phosphorylation and activation of MAPK/ERK and the inhibition of tumor cell proliferation. PD-0325901 is tested in clinical trials against non-small cell lung cancer, neurofibromatosis, melanoma and breast cancer.

Treosulfan (l-threitol-1,4-bis-methanesulfonate; dihydroxybusulfan) is a prodrug of a bifunctional alkylating cytotoxic agent that is approved for the treatment of ovarian carcinomas in a number of European countries. The antitumor activity of treosulfan has been shown in a variety of solid tumors. It is used for the treatment of all types of ovarian cancer, either supplementary to surgery or palliatively. Treosulfan is a prodrug that is converted nonenzymatically first to a mono-epoxide – (2S,3S)- 1,2-epoxy-3,4-butanediol-4-methanesulfonate – and then to a diepoxide – l-diepoxybutane, which is also a metabolite of butadiene – under physiological conditions. Such conversions are assumed to account for the alkylating and therapeutic activities of treosulfan.

CTP-656 is a deuterium-modified form of ivacaftor, an FDA-approved drug for the treatment of cystic fibrosis. CTP-656 is jointly developed by Concert Pharmaceuticals and Vertex Pharmaceuticals, and is believed to have higher metabolic stability, lower toxic byproducts and increased half-life compared to the original. CTP-656 acts as a potentiator of is a cystic fibrosis transmembrane conductance regulator (CFTR) protein. CTP-656 is investigated in phase 2 clinical trials for the treatment of cystic fibrosis.

Gavinostat is an orally bioavailable hydroxymate inhibitor of histone deacetylase (HDAC) with potential anti-inflammatory, anti-angiogenic, and antineoplastic activities. Gavinostat inhibits class I and class II HDACs, resulting in an accumulation of highly acetylated histones, followed by the induction of chromatin remodeling and an altered pattern of gene expression. At low, nonapoptotic concentrations, this agent inhibits the production of pro-inflammatory cytokines such as tumor necrosis factor- (TNF-), interleukin-1 (IL-1), IL-6 and interferon-gamma. It is currently in phase 2 trials for Myeloproliferative disorders, Polycythaemia vera and Phase III for Duchenne muscular dystrophy announced. In clinical trials of givinostat as a salvage therapy for advanced Hodgkin's lymphoma, the most common adverse reactions were fatigue, mild diarrhea or abdominal pain, moderate thrombocytopenia, and mild leukopenia.

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.

SSR-125543 is a potent, selective, and orally active corticotropin-releasing factor 1 receptor (CRF1) antagonist (Ki value of 2nM). SSR-125543 attenuates long-term cognitive deficit induced by acute inescapable stress in mice, independently from the hypothalamic pituitary adrenal axis. SSR-125543 prevents stress-induced cognitive deficit associated with hippocampal dysfunction. SSR-125543 had been in phase II clinical trials by Sanofi for the treatment of Post-traumatic stress disorder. It is also in phase I trials for the treatment of anxiety. The compound had also been in phase II clinical trials for the treatment of major depression. However, in 2011, the research was discontinued.

Vorasidenib (also known as AG 881) was developed as an isocitrate dehydrogenase (IDH) type 1 in the cytoplasm and type 2 in the mitochondria, with potential antineoplastic activity. It is known that IDH is an essential enzyme for cellular respiration in the tricarboxylic acid (TCA) cycle. Isocitrate dehydrogenases 1 and 2 (IDH1/2) are homodimeric enzymes that catalyze the conversion of isocitrate to α-ketoglutarate (α-KG) in the tricarboxylic acid cycle. Vorasidenib participated in phase I clinical trials in patients with advanced hematologic malignancies and in gliomas.