In this paper, two networks, namely, the target–target and drug–drug networks ( and ), were visualized using network analysis tools. The drug discovery status and trend were analyzed based on the new NMEs approved by the U.S. FDA from January 2000 to December 2009.
The average target number of sampled drugs from January 2000 to December 2009 is slightly higher than that of the drugs collected by Drugbank before May 2006 
. Moreover, the average target number of blockbuster drugs is also higher than that of all our collected samples 
. These observations indicate that multi-target drug discovery is indeed a status over the past decade and a possible trend in the future, although many single-target drugs are still used today. This development is primarily due to the recent changes in people’s lifestyles, leading to morbidity and alteration in the market share of therapeutic areas. The sales of drugs for nervous and cardiovascular system diseases and anti-neoplastic agents exceed the average sales of all drugs 
. In fact, cancer and those nervous and cardiovascular system diseases are complicated, thereby promoting the multi-targeted therapies as a better pathway to achieve the desired treatment. For example, the therapeutic targets for cancer include tubulin, topoisomerases, various types of tyrosine kinases, mammalian target of rapamycin, phosphatidylinositol 3-kinase, histone deacetylases, focal adhesion kinase, AMP-activated protein kinase (AMPK), 26S proteasome complex, and cyclooxygenase, among others 
; the therapeutic targets for Alzheimer’s disease include acetylcholinesterase, secretase, monoamine oxidase B, and τ protein, among others 
; the therapeutic targets for atherosclerosis include acylcoenzyme A-cholesterol acyltransferase, high density lipoprotein, lectin like oxidized low density lipoprotein receptor, AMPK, and peroxisome proliferator-activated receptor (PPAR), among others 
. It seems that using single-targeted agents to cure these complex diseases is almost impossible. The multiple tyrosine kinase inhibitor imatinib induces better anti-cancer effects compared with that of gefitinib, which involves a single target 
, further indicating that drugs with multiple targets may exhibit a better chance of affecting the complex equilibrium of whole cellular networks than drugs that act on a single target. Actually, there are several molecular targets, such as dopamine receptors, 5-hydroxytryptamine receptor, adrenergic receptors, cyclooxygenase, monoamine oxidase B, AMPK, PPAR, etc.
( and 
), are common to the complex human diseases, indicts that these targets may play vital roles in the development of complex disease and also suggests that drugs target these targets may have the potential for the secondary development.
Then, how do we develop multi-targeted drugs successfully? Although a number of marketed drugs are thought to derive their therapeutic benefit by interacting with multiple targets, majority of these were discovered accidentally. Therefore, the rational discovery of multi-target drugs is an emerging area. For instance, tyrosine kinases are good targets for the treatment of cancer, and several drugs have already been approved by the U.S. FDA. As targeting several tyrosine kinase receptors at once may dramatically affect the progression of cancer and decrease resistance, some multi-target tyrosine kinase inhibitors have been developed in the recent years 
. Though there are some studies for multi-target drug design in the recent years 
, it is still a long way to rationally design promising multi-target agents based on current knowledge. The most important thing is that we still not clear which targets should be combined to design better drugs for the specific complex diseases. As natural products are a rich reservoir for drug discovery because of their diversity and complexity structures 
and most of the natural products are multi-target, we propose that screening the new compounds from natural products based on high content screening is an effective strategy. It is also worthy to re-screening and re-evaluating the dirty compounds such as curcumin 
, berberine 
, and baicalein 
, among others. Of course it is worth noting that there are also several disadvantages of natural products, such as low bioavailability, weak effects, and complex molecular mechanism of actions, among others 
. Thus, structure modification using medicinal chemistry and pharmaceutical technologies and mechanisms identification using advanced modern technologies are necessary 
Combinatorial therapy is another kind of multi-target drug. The treatment of cancer in clinical is almost combination therapy and it is also increasingly used in the prevention and treatment of AIDS, cerebral ischemia, Parkinson’s disease, and Alzheimer’s disease, among others 
. What will happen if all known targets for one complex disease were simultaneously affected using one compound or drug combination? Identifying such compound or combination is actually impossible, and toxicity is another problem that will be raised. Thus, one better way is to combine the targets selectively according to the developing knowledge and screen the compounds for rational drug discovery. Therefore, the mechanisms causing a particular disease must be clarified. The rapid development of technologies in biological systems such as genomics, proteomics, metabonomics and so on, may enhance our understanding of the nature of the disease, effectively find possible therapeutic targets, and generate computer models that will identify the correct multi-fitting and further make this novel drug design paradigm successful.
In summary, we applied network analysis tools and successfully visualized the information. The approach may still have more or less biases. For example, some targets information may be changed due to the growth of knowledge. Nevertheless, we have confirmed the status of drug discovery in the recent years and put forward the possible future trend.