NK611

NK611 is a semisynthetic analogue of etoposide, classified as an epipodophyllotoxin derivative. It was developed as a potential anticancer agent with improved potency compared to etoposide. The drug acts through inhibition of topoisomerase II and has shown promising activity against various cancer cell lines in preclinical studies. ## Chemical Structure and Properties NK611 contains a dimethylamino group at the sugar moiety (D-glucose) instead of a hydroxyl group found in etoposide. This structural modification results in significant physicochemical differences - NK611 is much less hydrophobic than etoposide, which contributes to its improved bioavailability[8]. The molecular formula is C31H37NO12 with a molecular weight of 615.625 g/mol[7]. The drug is often used in its hydrochloride salt form (NK-611 hydrochloride, C31H38ClNO12)[3]. ## Development History NK611 was developed by Nippon Kayaku in Japan[2]. The drug underwent clinical evaluation, including Phase I and Phase II trials for various cancer indications. However, development appears to have been discontinued, as indicated by the development status listed as "Discontinued" for cancer and solid tumors[2]. ## Pharmacology and Mechanism of Action Like etoposide, NK611 acts through inhibition of topoisomerase II[1]. In preclinical studies, NK611 demonstrated equal or superior antitumor activity compared to etoposide in various in vitro and in vivo tumor models[6][8]. The drug showed concentration-dependent antitumor activity against freshly explanted clonogenic cells from human tumors[1]. ## Clinical Studies Phase I clinical trials evaluated NK611 administered as an intravenous infusion over 30 minutes. The maximum tolerated dose was determined to be 120 mg/m² without hematopoietic growth factor support and 200 mg/m² with G-CSF support[6]. Dose-limiting toxicities included granulocytopenia and thrombocytopenia, while non-hematologic toxicities consisted of alopecia, mild nausea, and infection[6]. Pharmacokinetic analyses revealed that NK611 follows a three-compartment model with a terminal half-life of approximately 14-15 hours. The drug exhibits high protein binding (98.7%)[6][8]. In clinical studies, partial responses were observed in patients with pleural mesothelioma, non-small cell lung cancer, and hepatocellular carcinoma[6]. An oral formulation of NK611 was also developed and evaluated in clinical trials[2][9]. Despite showing promising activity in early clinical studies, NK611 does not appear to have progressed to market approval, with development status listed as "Discontinued" for cancer and solid tumors[2].

Other names

NK611 hydrochlorideNK-611 hydrochlorideNK 611 hydrochloride