APTO-253 is a novel small molecule that can induce expression of the genes that code for the Krüppel-like factor 4 (KLF4) master transcription factor and for the p21 cell cycle inhibitor protein, and can inhibit expression of the c-Myc oncogene, leading to cell cycle arrest and programmed cell death (apoptosis) in human-derived solid tumor and hematologic cancer cells. A Phase 1 study with APTO-253 was completed and demonstrated modest clinical activity in patients with colon cancer, acute leukemia, myelodysplastic syndrome, hematological malignancies and non-small cell lung cancers.

Annamycin is a highly lipophilic form of the anthracycline doxorubicin with the ability to bypass multidrug resistance mechanisms of cellular drug resistance. Annamycin belongs to the anthracycline class of drugs, and has a pleiotropic mechanism of action where it targets topoisomerase II, causing strand breaks in DNA. Annamycin forms complexes with DNA by intercalation between base pairs, and it inhibits topoisomerase II activity by stabilizing the DNA-topoisomerase II complex, preventing the religation portion of the ligation-religation reaction that topoisomerase II catalyzes. The agent is being evaluated in separate phase 1 and phase 2 trials in the United States and Europe. Studies in animal models showed the agent to be noncardiotoxic. Trials that included patients with leukemia showed the agent was associated with fewer dose-limiting toxicities than typically experienced with doxorubicin. The FDA granted fast track designation to Annamycin for treatment of patients with relapsed or refractory acute myeloid leukemia.

CPI-613 is a lipoate derivative synthesized to be catalytically inert but to potentially mimic lipoate catalytic intermediates. The drug is in phase II of clinical trials for the treatment of Myelodysplastic syndromes; Pancreatic cancer; Small cell lung cancer; Solid tumors; Bile duct cancer; Acute Myeloid leukemia. The mechanism of CPI-613 action can be explained by (I) inhibition of tumor cell pyruvate dehydrogenase complex (PDC) through activation of pyruvate dehydrogenase kinases leading to inactivating phosphorylation of the E1alpha-subunit of PDC; and (II) inhibition of alpha-ketoglutarate dehydrogenase.

Tipifarnib is an oral farnesyltransferase (FTase) inhibitor which was developed by Janssen (J&J). Upon administration, tipifarnib inhibits FTase and thus suppresses the activity of downstream effectors. The drug reached phase III of clinical trials for such diseases as pancreatic cancer (terminated), colorectal cancer (terminated) and acute myeloid leukemia (in elderly patients).