Drug failures are common in cancer treatments and one of the major reasons is the heterogeneity of disease specific protein target expressions in cancer cells and therefore developing a targeted drug that can be effective on majority of the patient population has not been achieved yet. Conventional drug development approaches exdusively targeting protein biomolecules such as receptors, enzymes, hormones etc., and depends on the prior knowledge of their biological roles. As an alternative approach, we selected compounds targeting only cancer cells (e.g. HCC4017 lung cancer) in the presence of normal bronchial epithelial cells (e.g. HBEC30KT) derived from the same patient, applying our unique on-bead two-color combinatorial cell screen (JACS 130, 5744-5752, 2008; Current Protocols in Chemical Biology 4: 35-48, 2012) in an "unbiased" approach without knowing what they target at the beginning. But the idea here is; those selected compounds are targeting 'something' only found in cancer cell surface that is absent in normal cells and this 'something' can be a protein, lipid, carbohydrate, glycoprotein etc., which will be identified subsequently. This approach simply bypasses the time and resource consuming conventional drug development approach, which also rely on prior knowledge of the targeted biomolecule. We identified two peptidomimetic (peptoid) compounds PPSl (previously named as JM79) and PPS2 (previously named as JM258). These two compounds were identified in two separate screens, but have very similar structure. Later we found that both of these compounds are mainly targeting phosphatidylserine (PS), a lipid that predominantly express on outer layer of tumor cells, tumor endothelium and apoptotic cells as opposed to normal cells in the body, where PS is limited to inner layer of the cell membrane. Since PS is universally found in tumors, this has been considered as a global target for potential cancer therapeutics. Our compounds display low nanornolar binding affinity (Kd 15-20 nM) for PS with great specificity over phosphatidylcholine (PC - the typical lipid found on normal cells) on ELISA-like and liposome binding assays. The compound PPS1 binds around low μMon HCC4017 and H460 lung cancer cells that has been shown to express PS. More importantly, the simple dimeric version of this compound (PPS1D1) displays much improvement (about 175-fold) with binding at 80 nM (FACS studies) on these HCC4017 lung cancer cells. Compounds PPS1 and PPS2 able to pull down HCC4017 cells as well as a spectrum of lung cancer lines (about 10 cell lines) very selectively over normal HBEC30-kt and HBEC- 3kt cells, validated on magnetic bead pull down assay. On the activity side, PPS1D1 display strong in vitro cancer cell killing activity on lung cancer (e.g. HCC4017, H460, H358, H441, H1819, H1993, H2122 cells), breast cancer (MD-MB-231 cells) and prostate cancer (PC3 cells), validated to date using standard MTS cell viability assays and FACS studies. Recent in vivo studies indicated that PPSlDlstrongly accumulated in HCC4017 tumor xenograpfts in mice. PPSlDl displayed strong tumor burden effect on H460 lung cancer xenografts, even better than docitaxel - a standard chemotherapy. More importantly, the combination treatment of PPSlDl with Docetaxel almost wiped-out the tumor. By now, we have developed various derivatives of PPS1 that has similar and improved activities. The initial structural studies indicates that these compounds have a secondary structure in solution and mechanism of action studies indicates that these compounds are highly cell permeable with rapid cell killing activity. PS has been reported as a universal biomarker for tumors and tumor-microenvironment and following radiation and chemotherapy therapy, up to 95% of the tumor vessels can become PS-positive, making this an ideal and global candidate for both therapeutic and diagnostic applications. Also PS is known to express viral as well as infected cells, and therefore applications can be extended to anti-viral therapy as well. Furthermore, these peptoids are serum stable, non-immunogenic, highly diverse, more economical to synthesize and can be optimized at will, displaying precious collection of drug like characteristics. Finally, cancer is one of t he leading causes of deaths in US today and developing economical, biologically amenable and high specific agents targeting cancer at a 'global level' for both diagnostic and therapeutic applications are the top most clinical markets in US today.