Ravatirelin is a thiazolyl-alanine derivative patented by Japanese pharmaceutical company Shionogi & Co., Ltd. as a thyrotropin-releasing compound with improved central nerve activating effects such as sustained acetylcholine-releasing effect, and spontaneous motility increasing effect. Rovatirelin binds to the human thyrotropin-releasing hormone receptor with nanomolar affinity and increases the spontaneous firing of action potentials in the acutely isolated noradrenergic neurons of rat locus coeruleus. In in vivo studies, oral administration of Ravatirelin increased both c-Fos expression in the LC and extracellular levels of noradrenaline in the medial prefrontal cortex of rats. Furthermore, Ravatirelin increased locomotor activity. The increase in noradrenaline level and locomotor activity by Ravatirelin was more potent and longer acting than those by taltirelin. In phase I studies in healthy adult males, Ravatirelin exhibited linear pharmacokinetics in a single-ascending dose (0.1 to 10 mg) and a benign safety profile supportive of once-daily oral administration. From results of Phase II and III studies to evaluate the efficacy and safety of Ravatirelin in spinocerebellar degeneration patients, a daily dose of 1.6 to 3.2 mg of Ravatirelin has been considered to be dosage level intended for clinical use as once-daily oral administration.

G749 is a Fms-like tyrosine receptor kinase 3 (FLT3) inhibitor and a promising next-generation drug candidate for the treatment of relapsed and refractory acute myeloid leukemia (AML) patients with various FLT3-ITD/FLT3-TKD mutants that shows the ability to overcome drug resistance. It demonstrated potent and sustained inhibition of the FLT3 wild type and mutants including FLT3-ITD, FLT3-D835Y, FLT3-ITD/N676D, and FLT3-ITD/F691L in cellular assays. G749 retained its inhibitory potency in various drug-resistance milieus such as patient plasma, FLT3 ligand surge, and stromal protection. It also displayed potent antileukemic activity in bone marrow blasts from AML patients regardless of FLT3 mutation status, including those with little or only minor responses to AC220 or PKC412. Oral administration of G749 yielded complete tumor regression and increased life span in animal models.

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.