WntHedgehogNotch Pathway抑制剂整理版.doc

Wnt inhibitorsICG-001M.Wt:548.63Formula:C33H32N4O4Solubility:DMSO 110mg/mL Water 99%Storage:at -20 2 yearsCAS No.:780757-88-2Biological ActivityICG-001 is a selective Wnt/-catenin signalling inhibitor with an IC50 of 3M. After selectively binding of ICG-001 to the NH2 terminus of cyclic AMP response element binding protein (CREB), ICG-001 prevented beta-catenin/TCF signaling. ICG-001 elevated the activities of caspase in colon carcinoma cell lines, but not normal cells via down regulation of survivin. It is exhibited that ICG-001 rescues defects in neuronal differentiation and reverse pulmonary fibrosis. ICG-001 also suppressed the interaction between CREB and -catenin. 1ICG-001 selectively induces apoptosis in transformed cells but not in normal colon cells. And ICG-001 reduces in vitro growth of colon carcinoma cells. ICG-001 efficaciously treated the colon cancer in the Min mouse and nude mouse xenograft models. XAV 939M.Wt:312.31Formula:C14H11F3N2OSSolubility:DMSO 3mg/mL Water 99%Storage:at -20 2 yearsCAS No.:284028-89-3Biological ActivityXAV 939 is a small molecule and selective Wnt pathway transcription factor -catenin-mediated transcription inhibitor and axin stabilizing agent with IC50 of 11 and 4nM for the inhibition of TNKS1 and TNKS2, respectively. It stimulates beta-catenin degradation by stabilizing axin, the concentration-limiting component of the destruction complex and stabilizes axin by inhibiting the poly-ADP-ribosylating enzymes tankyrase 1 and tankyrase 2. Both tankyrase isoforms interact with a highly conserved domain of axin and stimulate its degradation through the ubiquitin-proteasome pathway. Deregulated Wnt/b-catenin pathway activity has been implicated in many cancers. Hedgehog inhibitorsCyclopamineM.Wt:411.62Formula:C27H41NO2Solubility:DMSO 6mg/mL Water 99%Storage:at -20 2 yearsCAS No.:4449-51-8Biological ActivityCyclopamine inhibits the hedgehog signaling pathway (Hh) by influencing the balance between the active and inactive forms of the Smoothened protein. The hedgehog signaling pathway carries out important functions in embryonic development and when it goes awry, deformities can occur. However, errant activation of the pathway can also trigger cancer in adult humans. 1Cyclopamine is a lipophilic compound extracted from the lily Veratrum californicum. It antagonizes Smo activity by binding to its heptahelical bundle. Thus, it can block pathway activation resulting in any of the two upstream events of Smoi.e., either from PTCH mutations or from Hh ligand over-expression. Cyclopamine is currently being investigated as a treatment agent in basal cell carcinoma, medulloblastoma, and rhabdomyosarcoma, tumors connected to excessive Hh activity,etc. 2In preclinical models of rodent and human prostate cancer, cyclopamine can inhibit tumor growth as well as tumor progression. Administration of cyclopamine causes both down-regulation of proliferation and initiation of apoptosis, with consequent reduction in tumor size. Administration of cyclopamine in a lethal, metastatic rodent model of prostate cancer completely abrogates systemic metastases and dramatically improves survivalGDC-0449 (Vismodegib)M.Wt:421.3Formula:C19H14Cl2N2O3SSolubility:DMSO 84mg/mL Water 99%Storage:at -20 2 yearsCAS No.:879085-55-9Biological ActivityGDC-0449 (Vismodegib) is a more potent novel and specific synthetic oral hedgehog pathway inhibitor with an IC50 of 3 nM. It targets the Hedgehog signaling pathway, blocking the activities of the Hedgehog-ligand cell surface receptors PTCH and/or SMO and suppressing Hedgehog signaling. The Hedgehog signaling pathway plays an important role in tissue growth and repair; aberrant constitutive activation of Hedgehog pathway signaling and uncontrolled cellular proliferation may be associated with mutations in the Hedgehog-ligand cell surface receptors PTCH and SMO. It inhibits the growth of primary pancreatic xenografts without non-specifically inhibiting pancreatic cell proliferation in vitro and has recently entered the clinic. It also inhibits ABCG2, Pgp, and MRP1-important ABC transporters associated with MDR. The IC50 values of GDC-0449 (Vismodegib) for inhibition of ABCG2 and Pgp were about1.4 and 3.0 M, respectively. It has been used to treat medulloblastoma in animal modelsLY2940680M.Wt:512.5Formula:C26H24F4N6OSolubility:DMSO 1mg/mL Water 99%Storage:at -20 2 yearsCAS No.:N/ABiological ActivityLY2940680 is a potent agent used to treat cancer. A study will explore the changes in a cancer marker level in skin, hair follicles and tumor cells. Finally, the study will help document any antitumor activity this drug may haveSMO inhibitorsLDE225 (NVP-LDE225)M.Wt:485.5Formula:C26H26F3N3O3Solubility:DMSO 97mg/mL Water 99%Storage:at -20 2 yearsCAS No.:956697-53-3Biological ActivityLDE225 (NVP-LDE225) is a novel and specific, orally bioavailable Smo inhibitor with an IC50 of 11 nM. It has been shown to potentially inhibit Hh-and Smo-dependent proliferation in vivo. It also induced the regression of preformed basaloid lesions with an IC50 of 150nmol/l and almost complete regression at 1.5mol/l. Topical application of a 1