Clinical candidate JNC-1043, importin ß inhibitor (first in class), to target incurable cancers, TNBC, and colon cancer.

Abstract

e15096 Background: JNC-1043 is an importin ß inhibitor, first in class drug candidate for TNBC (triple negative breast cancer) and incurable cancer therapy. JNC-1043 exhibits strong binding affinity to importin ß, and an excellent anti-cancer effect against various cancer cell lines and in vivo xenograft models. In addition, JNC-1043 exhibits radio-sensitizer effects by blocking of IR-induced invasion. Methods: JNC-1043 is evaluated in vitro against several cancer cell lines, TNBC, Lung, Ovarian, Gastric, Blood and other cancer cell lines and in vivo evaluation with two Xenograft models, TNBC and Colon cancer. PK and Toxicity study of JNC-1043 was carried out in Rats, Beagle dogs and/or Cynomolgus Monkeys. Results: Importin ß inhibitory effect and Cell viability (CC 50 ) of JNC-1043 show < 1.0 μM in the enzyme and 0.07~1.17 μM against various cancer cell lines, respectively. And 2 in vivo Xenograft models in PO administration for 10~14 days exhibit 75 % reduction of cancer size compared to MOCK control. PK profile of JNC-1043 PO dosing is excellent in SD Rats and Monkeys, T1/2 = 6.3 hr and 7.9 hr, respectively. Regarding Toxicity profile, once daily oral gavage administration to SD rats is well tolerated for 14 days at dose levels of 125, 250, 500 mg/kg/day. NOAEL after daily oral gavage dosing in rats for 14 days was determined to be more than 500 mg/kg/day. Conclusions: JNC-1043 is an importin ß inhibitor and promising clinical candidate for cancer therapy especially TNBC. This poster presents results of JNC-1043 studies that are MOA, in vitro and in vivo efficacy , PK and Tox. studies, and CMC.