Blog of Signaling Pathways

Oncogenic activation of JAK3-STAT signaling confers clinical sensitivity to PRN371, a novel selective and potent JAK3 inhibitor, in natural killer/T-cell lymphoma

295 views | Mar 03 2021

M -L Nairismägi found that the activity of PRN371 had a more durable inhibition on JAK3 compared to tofacitinib in vitro, leading to significant tumor growth inhibition in a NKTL xenograft model harboring JAK3 activating mutation. [Read the Full Post]

Manipulating bovine granulosa cell energy metabolism limits inflammation

640 views | Mar 03 2021

Anthony D Horlock et al. implied that energy stress compromised ovarian follicle immune defences. [Read the Full Post]

CBP Bromodomain Inhibition Rescues Mice From Lethal Sepsis Through Blocking HMGB1-Mediated Inflammatory Responses

299 views | Mar 02 2021

Xiaowen Bi et al. suggested that CBP bromodomain could serve as a candidate therapeutic target for the treatment of lethal sepsis via inhibiting LPS-induced expression and release of HMGB1 and suppressing the pro-inflammatory activity of HMGB1. [Read the Full Post]

Physcion, a novel inhibitor of 5α-reductase that promotes hair growth in vitro and in vivo

241 views | Mar 02 2021

Zizhao Lao et al. suggested that Physcion was a potent 5α-reductase inhibitor, as well as a new natural medicine for treating AGA. [Read the Full Post]

BTK gatekeeper residue variation combined with cysteine 481 substitution causes super-resistance to irreversible inhibitors acalabrutinib, ibrutinib and zanubrutinib

329 views | Mar 01 2021

H Yesid Estupiñán et al. found that reversible inhibitors showed a variable pattern, from resistance to no resistance, collectively demonstrating the structural constraints for different classes of inhibitors, which might affect their clinical application. [Read the Full Post]

CD8 lymphocyte depletion enhances the latency reversal activity of the SMAC mimetic AZD5582 in ART-suppressed SIV-infected rhesus macaques

205 views | Mar 01 2021

Maud Mavigner et al. suggested that the latency reversal induced by activation of the ncNF-κB signaling pathway with AZD5582 could be enhanced by CD8α+ cell depletion. [Read the Full Post]

Inhibition of ATM induces hypersensitivity to proton irradiation by upregulating toxic end joining

406 views | Feb 28 2021

Qin Zhou et al. found that inherent defects in HR or administration of an ATM inhibitor in HR proficient tumors selectively enhanced the relative biological effectiveness of proton Bragg peak irradiation. [Read the Full Post]

The role of acalabrutinib in adults with chronic lymphocytic leukemia

372 views | Feb 28 2021

Bita Fakhri et al. demonstrated superiority of the acalabrutinib-containing arms in terms of both efficacy and tolerability. [Read the Full Post]

Safety evaluation after acute and sub-chronic oral administration of high purity nicotinamide mononucleotide (NMN-C®) in Sprague-Dawley rats

285 views | Feb 26 2021

Cecile Cros et al. provided the first data highlighting the safety of short to intermediate term (sub-chronic) oral administration of NMN. [Read the Full Post]

Sensitization of head and neck squamous cell carcinoma to apoptosis by combinational SMAC mimetic and Fas ligand-Fc treatment in vitro

213 views | Feb 26 2021

Roman C Brands et al. identified SMAC mimetics, particularly BV-6 as the compound with the highest pro-apoptotic potency, as promising antitumor agents. [Read the Full Post]

Discovery of repurposing drug candidates for the treatment of diseases caused by pathogenic free-living amoebae

657 views | Feb 25 2021

Christopher A Rice et al. demonstrated the utility of phenotypic screens for discovery of new drugs for pathogenic free-living amoebae, including Acanthamoeba for the first time. [Read the Full Post]

Correction of eIF2-dependent defects in brain protein synthesis, synaptic plasticity, and memory in mouse models of Alzheimer's disease

445 views | Feb 24 2021

Mauricio M Oliveira et al. found that attenuating the ISR downstream of phosphorylated eIF2α might restore hippocampal protein synthesis and delay cognitive decline in AD patients. [Read the Full Post]

Priming with HDAC Inhibitors Sensitizes Ovarian Cancer Cells to Treatment with Cisplatin and HSP90 Inhibitors

619 views | Feb 24 2021

Ana J Rodrigues Moita et al. found that priming with HDACi sensitized ovarian cancer cells to treatment with HSP90i or cisplatin and had an influence on the development of cisplatin resistance, both of which might contribute to an improved ovarian cancer treatment. [Read the Full Post]

Structure-based discovery of 1H-indole-2-carboxamide derivatives as potent ASK1 inhibitors for potential treatment of ulcerative colitis

451 views | Feb 23 2021

Shaohua Hou et al. suggested that ASK1 inhibitors could potentially be used as a therapeutic strategy for UC. [Read the Full Post]

EGR1 knockdown alleviates the cerebral injury in rats with intracerebral hemorrhage (ICH) via STAT3/NF-κB pathway by reducing RXRα acetylation level

428 views | Feb 23 2021

Lijuan Xie et al. found that EGR1 increased RXRα acetylation level by regulating p300, thereby aggravating brain damage in ICH rat model and dysfunction in BMECs, which might through the STAT3/NF-κB pathway. [Read the Full Post]

Combating TKI resistance in CML by inhibiting the PI3K/Akt/mTOR pathway in combination with TKIs: a review

181 views | Feb 22 2021

Priyanka Singh et al. thought that the PI3K/Akt/mTOR signaling pathway in multiple cancers, might improve the therapeutic approaches towards TKI-resistant CML cells where the respective signaling pathway got upregulated. [Read the Full Post]

Selonsertib, a potential drug for liver failure therapy by rescuing the mitochondrial dysfunction of macrophage via ASK1-JNK-DRP1 pathway

455 views | Feb 22 2021

Guohua Lou et al. thought that selonsertib protected against LPS/GalN-induced ALF by attenuating JNK-mediated DRP1 mitochondrial translocation and then rescuing mitochondrial damage in macrophages and might have therapeutic potential for early ALF patients. [Read the Full Post]

More Insights on the Use of γ-Secretase Inhibitors in Cancer Treatment

597 views | Feb 21 2021

Pilar López-Nieva et al. suggested that selective targeting γ-secretase might offer an improved efficacy and toxicity profile over the effects caused by broad-spectrum GSIs. [Read the Full Post]

The dual PI3Kδ/CK1ε inhibitor umbralisib exhibits unique immunomodulatory effects on CLL T cells

0 views | Feb 21 2021

Kamira Maharaj et al. suggested that the improved safety profile of umbralisib was due to its role as a dual PI3Kδ/CK1ε inhibitor that preserved Treg number and function. [Read the Full Post]

Pazopanib (GW786034) and cyclophosphamide in patients with platinum-resistant, recurrent, pre-treated ovarian cancer - Results of the PACOVAR-trial

476 views | Feb 19 2021

C Dinkic et al. thought that Pazopanib 600mg daily p.o. and metronomic cyclophosphamide 50mg daily p.o. was a feasible regimen for patients with recurrent platinum-resistant EOC and showed promising activity in this previously treated patient population. [Read the Full Post]