Wnt Pathway Inhibitor

and CAGA12 reporter cell lines were activated with WntSa-conditioned medium, Forskolin, TNEa (tumor necrosis (actor alpha), and TGFp, respectively, and treated with 12-point dilutions of XAV939 or LDW643 (inactive analog). The corresponding reporter activity for each 

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Various components of the Wnt signaling pathway have been implicated in NTD. For example. Dull null mutants have thoracic spina bifida, and Dvll/2 double mutants produce even more severe NTD. Mutations of axin, a Wnt pathway inhibitor, can result in incomplete closure of the neural tube or malformation of the head folds. Alterations (hypoactivity, hyperactivity and missense mutations) to LRP6 can cause NTD. 

Fig. 3 Chemically mediated minimization of luciferase enzyme cross talk in multiplexed screening platforms. The RL inhibitors 12 and 23 (RLI12 and RLI23) exhibit >10-fold selectivity for RL over NL. These compounds could be used to eliminate inadvertent release of cytoplasmic RL into the medium where the typically secreted NL activity is found. The RLI compounds were identified as false positives from a high-throughput chemical screen for novel Wnt pathway inhibitors [3,8]...

Adenomatosis Polyposis Coli (APC). Whereas Dvl is a Wnt pathway activator, GSK3, Axin and APC are all inhibitors. Axin and APC help to stabilize the activity of GSK3, keeping (3-catenin levels low and Wnt target gene transcription off in the absence of a Wnt signal (Fig. 2a). 

Drugs currently used to treat osteoporosis are classified into those that inhibit osteoclastic bone resorption (including bisphos-phonates, denosumab, and selective estrogen receptor modulators) and those that stimulate bone formation by osteoblasts (parathyroid hormone and derivatives, such as teriparatide). Strontium ranelate may have a dual effect. Other drugs being tested in clinical trials include inhibitors of cathepsin K (an osteoclastic enzyme critical for bone resorption) and of sclerostin (a negative modulator of the Wnt pathway) [21],... 

In addition to growth factors, small molecules that induce the cardiogenesis pathway can enhance cardiomyocyte differentiation from hPSCs. A number of small molecules have been screened for promotion of cardiogenesis. The BMP signaling inhibitors [102, 103], p38 MAPKsignaling inhibitors [100], Wnt signaling activators [104], and Wnt singling inhibitors [105-107] are reported to promote the cardiac differentiation. 

Small-molecule inhibitors of the Wnt pathway potently promote cardiomyocytes from human embryonic stem cell-derived mesoderm. Circ Res 109(4) 360-364... 

Long Groucho/TLEs are transducin-like-enhancer of Split orthologs that function as the inhibitor of canonical Wnt pathway. The P-catenin and LEF/TCFs activation complexes are opposed by the LEF/TCF Groucho repressor complexes. The C-terminal WD repreat domain in Groucho/TLE is responsible for binding to LEF/TCFs. 

It is known that Wise is an inhibitor of canonical Wnt pathway and first identified as its ability to alter the antero-posterior characterstic of neuralized Xenopus animal caps by... 

SB-505124, both of which target the TbRI kinase domain, are in preclinical use. An alternative approach to inhibiting TGF- 3 signaling is to focus on the tumor suppressive function of this pathway. Promising future treatments will focus on pathways that are activated when the TGF-P signaling tumor suppressor pathway is inactivated. Examples are inhibitors to wnt signaling, CDK4 activation and IL-6. 

Besides the well-established Wnt/(3-catenin-dependent pathway components mentioned above, several additional cytoplasmic inhibitors of Wnt/ 3-catenin-dependent signaling have been identified that share... 

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