Blog of Signaling Pathways

NVP-LDE-225 (Erismodegib) Inhibits Epithelial-Mesenchymal Transition and Human Prostate Cancer Stem Cell Growth in NOD/SCID IL2Rγ Null Mice by Regulating Bmi-1 and microRNA-128

101 views | Apr 30 2020

R Nanta et al. suggested that inhibition of the Shh signaling pathway could therefore be a novel therapeutic option in treating prostate cancer. [Read the Full Post]

NVP-LDE225, a Potent and Selective SMOOTHENED Antagonist Reduces Melanoma Growth in Vitro and in Vivo

121 views | Apr 30 2020

Ahmad Jalili et al. concluded that inhibition of SHH-GLI signaling pathway in human melanoma by the specific smoothened inhibitor NVP-LDE225 could have potential therapeutic application in human melanoma even in the absence of BRAF(V600E) mutation and warrants further investigations. [Read the Full Post]

Caspase-3 Inhibitor Z-DEVD-FMK Enhances Retinal Ganglion Cell Survival and Vision Restoration After Rabbit Traumatic Optic Nerve Injury

111 views | Apr 28 2020

Yuanyuan Liu et al. showed the caspase-3 inhibitor Z-DEVD-FMK is neuroprotective by inhibiting RGCs apoptosis when injected 30 min after optic nerve damage and significantly promotes restoration of vision. A controlled clinical trial is now needed to evaluate the efficacy and safety of Z-DEVD-FMK in humans. [Read the Full Post]

Ricolinostat, the First Selective Histone Deacetylase 6 Inhibitor, in Combination With Bortezomib and Dexamethasone for Relapsed or Refractory Multiple Myeloma

143 views | Apr 27 2020

Dan T Vogl et al. showed that at the recommended phase II dose of ricolinostat of 160 mg daily, the combination with bortezomib and dexamethasone is safe, well-tolerated, and active, suggesting that selective inhibition of HDAC6 is a promising approach to multiple myeloma therapy. [Read the Full Post]

Covalent CDK7 Inhibitor THZ1 Inhibits Myogenic Differentiation

74 views | Apr 27 2020

Xinqi Ma et al. indicated that THZ1 inhibits myogenic differentiation, suggesting that therapies based on THZ1 might have potential side effects on muscle functions. [Read the Full Post]

A First-in-Human Phase I Study of the Oral p38 MAPK Inhibitor, Ralimetinib (LY2228820 Dimesylate), in Patients With Advanced Cancer

90 views | Apr 26 2020

Amita Patnaik et al. demonstrated acceptable safety, tolerability, and pharmacokinetics for patients with advanced cancer. [Read the Full Post]

Characterization of LY2228820 Dimesylate, a Potent and Selective Inhibitor of p38 MAPK With Antitumor Activity

77 views | Apr 26 2020

Robert M Campbell et al. showed that LY2228820 is a p38 MAPK inhibitor, which has been optimized for potency, selectivity, drug-like properties (such as oral bioavailability), and efficacy in animal models of human cancer. [Read the Full Post]

YH25448, an Irreversible EGFR-TKI With Potent Intracranial Activity in EGFR Mutant Non-Small Cell Lung Cancer

183 views | Apr 23 2020

Jiyeon Yun et al. suggested that YH25448 is a promising third-generation EGFR inhibitor, which may be more effective and better tolerated than the currently approved osimertinib. [Read the Full Post]

Safety and Antitumor Activity of Apalutamide (ARN-509) in Metastatic Castration-Resistant Prostate Cancer With and Without Prior Abiraterone Acetate and Prednisone

73 views | Apr 23 2020

Dana E Rathkopf et al. indicated that apalutamide was safe, well tolerated, and demonstrated clinical activity in mCRPC, with 80% of AAP-naïve and 43% of post-AAP patients, remaining on treatment for 6 months or longer. [Read the Full Post]

Design, Synthesis and Biological Evaluation of 2-amino-4-(1,2,4-triazol)pyridine Derivatives as Potent EGFR Inhibitors to Overcome TKI-resistance

149 views | Apr 22 2020

Haikui Yang et al. provided 2-amino-4-(1,2,4-triazol)pyridines as a new scaffold for EGFRT790M and/or EGFRvⅢ inhibitor. [Read the Full Post]

The Syk Inhibitor R406 Is a Modulator of P-glycoprotein (ABCB1)-mediated Multidrug Resistance

125 views | Apr 21 2020

George E Duran et al. indicated that the chemo-sensitizing effect of R406 in taxane-resistant cells previously reported was not associated with Syk but resulted from the modulation of P-gp-mediated MDR. [Read the Full Post]

The Mechanism of Action of Cyclosporin A and FK506

69 views | Apr 21 2020

S Ho et al. included those required for B-cell help such as interleukin (IL-4) and CD40 ligand as well as those necessary for T-cell proliferation such as IL-2. The purpose of this article is to illustrate the means by which these drugs produce immunosuppression. [Read the Full Post]

GANT61 Alleviates Arthritic Symptoms by Targeting Fibroblast-Like Synoviocytes in CIA Rats

129 views | Apr 20 2020

Suping Qin et al. indicated the GANT61 inhibit the proliferation of FLS and alleviated the arthritic symptoms in CIA rats, this implied the GANT61 may be recommended as a possible candidate for the therapy of RA. [Read the Full Post]

A Phase I Study of PF-04929113 (SNX-5422), an Orally Bioavailable Heat Shock Protein 90 Inhibitor, in Patients With Refractory Solid Tumor Malignancies and Lymphomas

142 views | Apr 19 2020

Arun Rajan et al. showed that PF-04929113 administered orally twice a week is well tolerated and inhibits its intended target Hsp90. No objective responses were seen, but long-lasting stabilizations were obtained. Although no clinically significant drug-related ocular toxicity was seen in this study, the development of PF-04929113 has been discontinued because of ocular toxicity seen in animal models and in a separate phase I study. [Read the Full Post]

SNX-2112, a Selective Hsp90 Inhibitor, Potently Inhibits Tumor Cell Growth, Angiogenesis, and Osteoclastogenesis in Multiple Myeloma and Other Hematologic Tumors by Abrogating Signaling via Akt and ERK

149 views | Apr 19 2020

Yutaka Okawa et al. provided the framework for clinical studies of SNX-2112 to improve patient outcome in MM and other hematologic malignancies. [Read the Full Post]

The BET Bromodomain Inhibitor i-BET151 Impairs Ovarian Cancer Metastasis and Improves Antitumor Immunity

96 views | Apr 15 2020

Ai Liu et al. showed that tumor metastasis may be suppressed by i-BET151 via the Stat3 pathway; this approach could be used as a strategy for the treatment of OC. [Read the Full Post]

Targeting Bromodomain and Extra-Terminal (BET) Family Proteins in Castration-Resistant Prostate Cancer (CRPC

110 views | Apr 15 2020

Jonathan Welti et al. showed that BETi merit clinical evaluation as inhibitors of AR splicing and function, with trials demonstrating their blockade in proof-of-mechanism pharmacodynamic studies. [Read the Full Post]

Rac1 plays a role in CXCL12 but not CCL3-induced chemotaxis and Rac1 GEF inhibitor NSC23766 has off target effects on CXCR4

87 views | Apr 14 2020

Mills SC et al. suggest that Rac1 activation is not necessary for CCL3 signalling, and reveal that NSC23766 could be a novel CXCR4 receptor ligand. [Read the Full Post]

Targeting Myosin by Blebbistatin Derivatives: Optimization and Pharmacological Potential

77 views | Apr 14 2020

Rauscher AÁ et al. discussed the pharmacological perspectives of these efforts, as myosins are becoming promising drug target candidates for a variety of conditions ranging from neurodegeneration to muscle disease, wound healing, and cancer metastasis. [Read the Full Post]

OTX015 (MK-8628), a novel BET inhibitor, displays in vitro and in vivo antitumor effects alone and in combination with conventional therapies in glioblastoma models

90 views | Apr 13 2020

Berenguer-Daizé C et al. demonstrated with OTX015 tumor levels 7 to 15-fold higher than in normal tissues, along with preferential binding of OTX015 to tumor tissue. The significant antitumor effects seen with OTX015 in GBM xenograft models highlight its therapeutic potential in GBM patients, alone or combined with conventional chemotherapies. [Read the Full Post]