Tamibarotene

Tamibarotene is an orally available, novel synthetic retinoid which was rationally designed to potentially improve drugable properties of all trans-retinoic acid (ATRA), the current first line treatment for APL. Tamibarotene shows lesser toxic side effects and higher pharmacological activities than ATRA. Pharmacological activities of tamibarotene are mediated by retinoic acid receptor (RARα), one of nuclear receptors and also a transcription factor, which is bound to DNA as a heterodimer with the retinoid X receptor (RXR) . Tamibarotene binds and activates RARα/RXR and then activated receptor binds retinoic acid responsive element (RARE) and either induces or represses transcription of a nearby gene.

The efficacy of tamibarotene against APL was demonstrated in two Phase 2 studies conducted in Japan in which a total of 63 patients including 58 relapsed patients were analyzed for the efficacy. The number and rate of patients achieving complete response were 38 and 60%, respectively. Tamibarotene is currently approved for relapsed or refractory APL in Japan.

Tamibarotene (TM-411, Am-80, TOS-80T, SY-1425)
Indication	Acute myeloid leukemia (AML)
	Myelodysplatic syndrome (MDS)
	Breast cancer (BC)
	Pediatric cancer
	Acute promyelocytic Leukemia (APL)
	Neuroblastoma (NB)
	Neutropenia (NP)
	Other possible indications Hepatocellular carcinomar (HCC) Multiple myeloma (MM)
Mechanisms of Action	NP： Differentiation induction from hematopoietic stem cells to neutrophil
	APL： Apoptosis through differentiation induction of APL cells
Dose & Administration	NP： Tablet/Soft capsule
	APL： Tablet
	Pediatric cancer： Soft capsule
Originator	Toko Pharmaceutical Industries Co.,Ltd. /KEMPHYS LTD.