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Blog of Signaling Pathways

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

126 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

70 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

130 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

144 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

150 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

97 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

111 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

88 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

78 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

91 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]

A phase II study to evaluate LY2603618 in combination with gemcitabine in pancreatic cancer patients

88 views | Apr 13 2020

Laquente B et al. showed that LY2603618/gemcitabine was not superior to gemcitabine for the treatment of patients with pancreatic cancer. [Read the Full Post]

Effects of a checkpoint kinase inhibitor, AZD7762, on tumor suppression and bone remodeling

84 views | Apr 12 2020

Wang L et al. indicated that in addition to acting as a tumor suppressor, AZD7762 may prevent bone loss by inhibiting osteoclastogenesis and stimulating osteoblast mineralization. [Read the Full Post]

Identifying off-target effects of etomoxir reveals that carnitine palmitoyltransferase I is essential for cancer cell proliferation independent of β-oxidation

119 views | Apr 12 2020

Yao CH et al. suggested that transport of at least some long-chain fatty acids into the mitochondria by CPT1 may be required for anabolic processes that support healthy mitochondrial function and cancer cell proliferation independent of FAO. [Read the Full Post]

Notch signaling pathway is a potential therapeutic target for extracranial vascular malformations

0 views | Apr 11 2020

Davis RB et al. provided further rationale to support testing of Notch inhibitors in patients with extracranial vascular malformations. [Read the Full Post]

Attenuated isolated 3' signal: A highly challenging therapy relevant ALK FISH pattern in NSCLC

127 views | Apr 11 2020

Smuk G et al. indicated the adequate therapy with higher efficiency for patients suffering from NSCLC. [Read the Full Post]

Drug resistance occurred in a newly characterized preclinical model of lung cancer brain metastasis

169 views | Apr 10 2020

Shah N et al. demonstrated that brain metastases of lung cancer cells may independently prompt drug resistance without drug treatment. [Read the Full Post]

Impact of high on-treatment platelet reactivity after angioplasty in patients with peripheral arterial disease

192 views | Apr 10 2020

Busch L et al. suggested that MALE might be associated with dual HTPR. [Read the Full Post]

Targeting NAD+ biosynthesis overcomes panobinostat and bortezomib-induced malignant glioma resistance

187 views | Apr 09 2020

Jane EP et al. provided new insights into mechanisms of treatment resistance in gliomas, hold promise for targeting recurrent disease, and provided a potential strategy for further exploration of next generation inhibitors. [Read the Full Post]

Sphingosine Kinase 1 in Breast Cancer-A New Molecular Marker and a Therapy Target

170 views | Apr 09 2020

Alshaker H et al. concluded that SK1 may have a potential as a target for precision medicine, its high expression being a negative prognostic marker in ER-negative breast cancer, as well as a target for chemosensitization therapy. [Read the Full Post]

Development Of Novel Liposome-Encapsulated Combretastatin A4 Acylated Derivatives: Prodrug Approach For Improving Antitumor Efficacy

96 views | Apr 08 2020

Gu Y et al. suggested that the release or hydrolysis of the parent drug from the prodrug was closely related with the in vitro and in vivo properties. The slow drug release of CA4 modified with longer acyl chain could prolong the circulation time and increase the concentration of the drug in the tumor tissue. These effects play a critical role in increasing the antitumor efficacy. [Read the Full Post]