Roniciclib (BAY1000394) is a pan-cyclin-dependent kinase inhibitor that has been developed for treatment in small cell lung carcinoma and solid tumors. Roniciclib targets certain key proteins that are essential for the survival of cancer cells, resulting in decreased tumor growth. Phase I studies to evaluate the safety, tolerability and pharmacokinetics of roniciclib have been completed successfully. In phase II studies, roniciclib was found to be well tolerated and showed promising efficacy when combined with chemotherapy in small cell lung carcinoma patients. However, due to an observed safety signal (treatment-emergent adverse events) in one phase II study, other clinical trials have been discontinued and further development of roniciclib was terminated.

Flumatinib (HHGV678) is an orally bioavailable antineoplastic tyrosine kinase inhibitor. Flumatinib inhibits the wild-type forms of Bcr-Abl, platelet-derived growth factor receptor (PDGFR) and mast/stem cell growth factor receptor (SCFR; c-Kit) and forms of these proteins with certain point mutations. Flumatinib was extensively metabolized after oral administration, and the major metabolic pathways observed were amide hydrolysis, demethylation, oxidation, and glucuronide conjugation. It is in phase III clinical trials for the treatment of Chronic myeloid leukemia (in China).

AT7519M or AT7519, a small molecule inhibitor of cyclin-dependent kinases 1, 2, 4, 5, and 9, participated in phase II clinical trials in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL). As a result, in CLL, some patients had tumor reductions, but the objective response rate (ORR) was low. In MCL, activity was noted with ORR of 27%. In addition, AT7519M was studied in patients with previously treated multiple myeloma, to understand whether the drug alone or in combination with bortezomib were effective treatments. Recent experiments also have shown that AT7519 is a promising drug for the treatment of high-risk neuroblastoma patients with MYCN amplification. It is known, that MYCN-dependent neuroblastomas have low cure rates with current multimodal treatment.

P276-00 (also known as riviciclib) is a novel, potent, small-molecule, flavone-derived inhibitor of cyclin-dependent kinases (Cdk), Cdk 4 D1, Cdk1 B, and Cdk9 T, with potent cytotoxic effects against chemosensitive and chemoresistant cancer cell lines. P276-00 was in phase II clinical trial for the treatment mantle cell lymphoma, but that study was terminated based on interim results and all subjects were off study at that time. Although, there were not the major safety or tolerability concerns. However, this drug successfully passed phase II clinical trial for the treatment Melanoma, squamous cell carcinoma of head and neck, malignant melanoma and in combination with Gemcitabine in the treatment of advanced pancreatic cancer.

Sapitinib is an oral, reversible and equipotent inhibitor of EGFR, HER2 and HER3 signalling. The drug was tested in phase II of clinical trials in patients with breast cancer, colorectal cancer, gastric cancer and NSCL carcinoma, however its development for breast cancer therapy seems to be terminated. Sapitinib absorption is rapid and the drug is totally cleared by metabolism with the major routes being oxidation and amine or ether cleavage around the piperidine ring with subsequent glucuronide or sulphate conjugation.

PF-04217903 is a triazolopyrazine inhibitor of c-MET that displays anticancer chemotherapeutic and anti-metastatic activities. PF-04217903 inhibits cell proliferation, invasion, and migration as well as tumor growth in various cancer models. In animal models of pancreatic neuroendocrine tumors, this compound prevents lymph node metastasis. PF-04217903 had been in phase I clinical trials by Pfizer for the treatment of solid tumors. In 2011, the company discontinued the development of the compound.

Sapanisertib is an oral dual inhibitor of mTORC1/mTORC2, discovered by Intellikine for the treatment of cancer. The drug is being tested in phase II of clinical trials for different cancers among which are sarcoma, hepatocellular carcinoma, etc. The drug is currently developed by Takeda with breast cancer, renal cancer and endometrial cancer being the main target indications.

Defactinib is an oral, investigational drug candidate for the treatment of various solid tumors. Through dual inhibition of FAK and PYK2, defactinib targets key resistance mechanisms in the tumor microenvironment (TME), including limited local immune response, dense stroma, and resident cancer stem cells, that may limit the effectiveness of current and investigational treatments. Treatment-related adverse events are: unconjugated hyperbilirubinemia, fatigue and headache.

LY-3009120 is an orally available inhibitor of all members of the serine/threonine protein kinase Raf family, including A-Raf, B-Raf, and C-Raf protein kinases, with potential antineoplastic activity. Upon administration, pan-RAF kinase inhibitor LY3009120 inhibits Raf-mediated signal transduction pathways, which may inhibit tumor cell growth. Raf protein kinases play a key role in the RAF/mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling pathway, which is often dysregulated in human cancers and plays a key role in tumor cell proliferation and survival. LY3009120 is being investigated in phase I clinical trial.