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Blog of Signaling Pathways

The Second-Generation Exportin-1 Inhibitor KPT-8602 Demonstrates Potent Activity Against Acute Lymphoblastic Leukemia

90 views | Mar 01 2020

Thomas Vercruysse et al. showed that KPT-8602 is highly specific for XPO1 inhibition and demonstrates potent anti-leukemic activity supporting clinical application of the second-generation SINE compound for the treatment of ALL. [Read the Full Post]

URMC-099 Facilitates Amyloid-β Clearance in a Murine Model of Alzheimer's Disease

245 views | Mar 01 2020

Tomomi Kiyota et al. indicated that URMC-099 facilitates Aβ clearance in the brain of APP/PS1 mice. The multifaceted immune modulatory and neuroprotective roles of URMC-099 make it an attractive candidate for ameliorating the course of AD. This is buttressed by removal of pathologic Aβ species and restoration of the brain's microenvironment during disease. [Read the Full Post]

Nuclear-Cytoplasmic Transport Is a Therapeutic Target in Myelofibrosis

99 views | Feb 28 2020

Dongqing Yan et al. implicated NCT as a potential therapeutic target in myelofibrosis and provide a rationale for clinical evaluation in ruxolitinib-exposed patients with myelofibrosis. [Read the Full Post]

An in vitro assay for biomarker discovery and dose prediction applied to ibrutinib plus venetoclax treatment of CLL

73 views | Feb 27 2020

Eide CA et al. suggested that IBR + VEN may represent an effective therapeutic option for patients with AML. [Read the Full Post]

Venetoclax, a BCL-2 Inhibitor, Enhances the Efficacy of Chemotherapeutic Agents in Wild-Type ABCG2-Overexpression-Mediated MDR Cancer Cells

75 views | Feb 27 2020

Wang JQ et al. provided useful guidance in combination therapy against wild-type ABCG2-mediated MDR cancer in clinical practice. [Read the Full Post]

Blocking PD1/PDL1 Interactions Together With MLN4924 Therapy Is a Potential Strategy for Glioma Treatment

96 views | Feb 26 2020

Natalia Filippova et al. concluded that i) PDL1 up-regulation in gliomas and the glioma microenvironment is an important chemotherapeutic target; ii) MLN4924 therapy, combined with a blockage of the PD1/PDL1 pathway, should be considered as a potential strategy for glioma treatment. [Read the Full Post]

The Syk Inhibitor Fostamatinib Disodium (R788) Inhibits Tumor Growth in the Eμ- TCL1 Transgenic Mouse Model of CLL by Blocking Antigen-Dependent B-cell Receptor Signaling

139 views | Feb 26 2020

Mirza Suljagic et al. provided further rationale for clinical trials with R788 in CLL and establish the BCR-signaling pathway as an important therapeutic target in this disease. [Read the Full Post]

Vismodegib in patients with advanced basal cell carcinoma: Primary analysis of STEVIE, an international, open-label trial

194 views | Feb 25 2020

Basset-Séguin N et al. showed the primary analysis of STEVIE demonstrates that vismodegib is tolerable in typical patients in clinical practice; safety profile is consistent with that in previous reports. Long-term exposure was not associated with worsening severity/frequency of TEAEs. Investigator-assessed response rates showed high rate of tumour control. [Read the Full Post]

Clinical activity and molecular correlates of response to atezolizumab alone or in combination with bevacizumab versus sunitinib in renal cell carcinoma

217 views | Feb 25 2020

McDermott DF et al. suggested that prediction of outcomes with anti-VEGF and immunotherapy may be possible and offer mechanistic insights into how blocking VEGF may overcome resistance to immune checkpoint blockade. [Read the Full Post]

Randomized Trial of Verubecestat for Prodromal Alzheimer's Disease

112 views | Feb 23 2020

Michael F Egan et al. indicated that verubecestat did not improve clinical ratings of dementia among patients with prodromal Alzheimer's disease, and some measures suggested that cognition and daily function were worse among patients who received verubecestat than among those who received placebo. [Read the Full Post]

Crenigacestat, a Selective NOTCH1 Inhibitor, Reduces Intrahepatic Cholangiocarcinoma Progression by Blocking VEGFA/DLL4/MMP13 Axis

351 views | Feb 23 2020

Serena Mancarella et al. developed and validated a new iCCA PDX model to test in vivo the activity of LY3039478, demonstrating its inhibitory role in Notch-dependent angiogenesis. Thus, the present data provide new knowledge on Notch signaling in iCCA, and support the inhibition of the Notch cascade as a promising strategy for the treatment of this disease. [Read the Full Post]

BACE1 Inhibitor MK-8931 Alters Formation but Not Stability of Dendritic Spines

106 views | Feb 20 2020

Tanja Blume et al. suggested that carefully dosed inhibitors might be therapeutically effective without affecting the structural integrity of excitatory synapses if given at an early disease stage. [Read the Full Post]

Adavosertib (AZD1775) in Combination With Gemcitabine and Radiation for Patients With Locally Advanced Pancreatic Cancer

99 views | Feb 20 2020

Kyle C Cuneo et al. indicated that AZD1775 in combination with gemcitabine and radiation therapy was well tolerated at a dose that produced target engagement in a surrogate tissue. The overall survival is substantially higher than prior results combining gemcitabine with radiation therapy and warrants additional investigation. [Read the Full Post]

Repotrectinib (TPX-0005), Effectively Reduces Growth of ALK Driven Neuroblastoma Cells

364 views | Feb 19 2020

Diana Cervantes-Madrid et al. showed that repotrectinib is capable of inhibiting signaling activity of a range of ALK mutant variants found in neuroblastoma patients and importantly it exhibits strong antitumor effects in a xenograft model of neuroblastoma. [Read the Full Post]

Repotrectinib (TPX-0005), Effectively Reduces Growth of ALK Driven Neuroblastoma Cells

0 views | Feb 19 2020

Diana Cervantes-Madrid et al. showed that repotrectinib is capable of inhibiting signaling activity of a range of ALK mutant variants found in neuroblastoma patients and importantly it exhibits strong antitumor effects in a xenograft model of neuroblastoma. [Read the Full Post]

Effects of the Preparation Method on the Formation of True Nimodipine SBE-β-CD/HP-β-CD Inclusion Complexes and Their Dissolution Rates Enhancement

178 views | Feb 18 2020

Farouk Semcheddine et al. showed that all the products exhibited higher dissolution rate than those of the physical mixtures and ND alone, in all mediums. However, the kneading complexes displayed the maximum dissolution rate in comparison with drug and other complexes, confirming the influence of the preparation method on the physicochemical properties of the products. [Read the Full Post]

Rapamycin Combined With MCC950 to Treat Multiple Sclerosis in Experimental Autoimmune Encephalomyelitis

159 views | Feb 18 2020

Ling Xu et al. provided theoretical support to the therapeutic evaluation of RAPA and MCC950 to make the mammalian targets of RAPA and NLRP3 the therapeutic targets of MS. [Read the Full Post]

AZD1208, a Pan-Pim Kinase Inhibitor, Has Anti-Growth Effect on 93T449 Human Liposarcoma Cells via Control of the Expression and Phosphorylation of Pim-3, mTOR, 4EBP-1, S6, STAT-3 and AMPK

138 views | Feb 17 2020

Yadav AK et al. demonstrated that AZD1208 inhibits growth of liposarcoma cells and that this activity is mediated through Pim-3 kinase, STAT-3, mTOR, S6 and AMPK expression and phosphorylation pathways. [Read the Full Post]

Targeting KRAS Mutant Cancers With a Covalent G12C-Specific Inhibitor

108 views | Feb 17 2020

Matthew R Janes et al. provided in vivo evidence that mutant KRAS can be selectively targeted and reveals ARS-1620 as representing a new generation of KRASG12C-specific inhibitors with promising therapeutic potential. [Read the Full Post]

Administration of Lapatinib with Food Increases Its Plasma Concentration in Chinese Patients with Metastatic Breast Cancer: A Prospective Phase II Study

201 views | Feb 16 2020

Xu F et al. showed that receiving lapatinib with food can increase its plasma concentration with no significantly increased drug-related toxicity. We suggest that a larger-sample-size clinical trial is needed to fully understand the effect of administration of lapatinib with food. [Read the Full Post]