**Synthetic Anti-cancer Drugs**

#### **SHetA2, a New Cancer-Preventive Drug Candidate SHetA2, a New Cancer-Preventive Drug Candidate**

Shengquan Liu, Guangyan Zhou, Sze Ngong Henry Lo, Maggie Louie and Vanishree Rajagopalan Shengquan Liu, Guangyan Zhou, Sze Ngong Henry Lo, Maggie Louie and Vanishree Rajagopalan

Additional information is available at the end of the chapter Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/65365

#### **Abstract**

SHetA2 (NSC 721689) is a novel synthetic flexible heteroarotinoid that has promising cancer-preventive activity, and has exhibited growth inhibition on 60 cancer cell lines in vitro, along with ovarian, lung, and kidney cancers *in vivo*. It binds and interferes with the function of a molecular chaperone, mortalin, leading to mitochondrial swelling and mitophagy that induce apoptosis in cancer cells without harming normal cells. It showed minimal toxicity in preclinical studies and thus is now in Phase-0 clinical trial. This chapter summarizes its evolution, synthesis, structure-activity relationship, mechanism of action, pharmacokinetics, and potential clinical applications in last 12 years. It also provides insights into designing more potent and safer SHetA2 analogs for future cancer-preventive drug development.

**Keywords:** SHetA2, flexible heteroarotinoids, apoptosis, cancer prevention, ovarian cancer
