BMPs and Urology statin, a member of the TGF-β superfamily and a known regulator of muscle mass, resulted in significant muscle mass increases [64]. Specifically, adult mice were treated with anti-myostatin antibodies, a soluble form of the acti- vin type IIB receptor (ActR-IIB), designated as ActRIIB-Fc (fragment crystallizable), and demonstrated a significant increase in muscle mass. Hence, myostatin is a potential therapeutic target for the treatment of various muscle- wasting diseases such as Duchenne muscular dystrophy (DMD), cachexia, and sarcopenia. Similarly, Natsume et al investigated the effect of extracellular domain type I re- ceptor for BMP-2 and 4 by using a silkworm expression sys- tem and reported that this soluble form of BMP receptor (sBMPR) binds to BMPs tightly [65]. Indeed, sBMPR can act as a potent BMP antagonist by specifically binding to active forms of BMP-2 and 4. 　In addition to the above macromolecules, small molecule inhibitors are chemical compounds that can act as selective inhibitory regulators of BMP signaling. To date, small mol- ecule inhibitors have become a useful pharmacological tool for dissecting the mechanisms of signaling pathways in many biological processes associated with TGF-β signal- ing. For example, SB-431542 is a small molecule inhibitor that is a potent and specific inhibitor of TGF-β type I activin receptor-like kinase (ALK) receptors ALK4, ALK5, and ALK7 [66]. As such, SB-431542 has the potential to be a novel therapeutic agent for diverse human diseases in which TGF-β signaling has been implicated [67]. Similarly, Lee et al reported that IN-1130 is a relatively nontoxic and potent small molecule inhibitor of ALK4, ALK5, and ALK7 that inhibits TGF-β signaling as well as activin and nodal signaling [68]. In prostate cancer cell lines, IN-1130 ex- hibited an antitumor effect by blocking the immunosup- pressive effects of the TGF-β signaling. 　Small molecule inhibitors of BMP receptor kinases have recently been reported. Using an in vivo screening assay based on zebrafish, Yu et al identified a specific small mole- cule inhibitor of BMP signaling, dorsomorphin [23]. Further studies revealed that dorsomorphin inhibits BMP type I receptors ALK2, ALK3, and ALK6 and blocks sub- sequent phosphorylation of Smad1, 5, and 8 and target gene transcription [69]. Small molecule inhibitors, such as dorsomorphin, are relatively inexpensive, can penetrate many cell layers easily, and may be orally bioavailable. Thus, these inhibitors may be effective therapies for hu- man pathologies associated with increased BMP signaling. CONCLUSIONS Reflecting their critical roles, BMPs are tightly regulated at multiple levels throughout their signal cascades. Extracellular endogenous antagonists, such as noggin and chordin, directly bind to BMP and sequester the activated ligands. In the cytoplasm, there are inhibitory Smads as well as Sno/Ski and Smurfs that regulate the R-Smad/ Co-Smad interaction and R-Smad degradation, respec- tively. 515 　Because the overexpression of BMPs has been im- plicated in a variety of human diseases including genito- urinary malignancies, actively inhibiting BMP signaling may be an effective therapeutic approach in some patients. To this end, neutralizing antibodies and soluble receptor domains have been explored. Alternatively, dorsomor- phin, the first small molecule inhibitor of BMP receptor type I, has been reported. As additional small molecule in- hibitors are identified and characterized, it is likely that new therapeutics for various diseases will be discovered. Before initiating clinical trials that target BMP signaling pathways, the biology of BMPs and the regulatory mecha- nisms must be clarified. 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