Blog of Signaling Pathways

Resistance to Pyrrolobenzodiazepine Dimers Is Associated with SLFN11 Downregulation and Can Be Reversed through Inhibition of ATR

66 views | Jun 30 2023

This study identified downregulation of Schlafen family member 11 (SLFN11) and its association with PBD resistance in cancer cells, highlighting the potential of targeting SLFN11 and combining ATR inhibitors to overcome resistance to PBD-conjugated ADCs. [Read the Full Post]

Delayed NLRP3 inflammasome inhibition ameliorates subacute stroke progression in mice

48 views | Jun 30 2023

The study found that inhibiting the NLRP3 inflammasome in the subacute phase of ischemic stroke reduced infarct size, improved functional outcomes, and mitigated local neuroinflammation, suggesting its potential as a pharmacological target for delayed treatment options. [Read the Full Post]

Butyrate dictates ferroptosis sensitivity through FFAR2-mTOR signaling

36 views | Jun 30 2023

Sodium butyrate enhances cell ferroptosis and inhibits tumor growth through downregulation of SLC7A11 and GPX4, mediated by the FFAR2-AKT-NRF2 and FFAR2-mTORC1 axes in a cAMP-PKA-dependent manner. [Read the Full Post]

The effect of sex on retinopathy of prematurity severity among premature mixed-sex multiple gestation infants

42 views | Jun 29 2023

This retrospective study of 68 premature infants found no significant difference between male and female mixed-sex multiple gestation infants in terms of the most severe stage of retinopathy of prematurity (ROP) developed or the need for ROP treatment, but males received treatment at an earlier postmenstrual age (PMA) despite females having lower birthweight and slower growth velocity. [Read the Full Post]

Identifying a selective inhibitor of autophagy that targets ATG12-ATG3 protein-protein interaction

48 views | Jun 29 2023

Compound 189, identified through a high throughput compound screen, selectively inhibits the ATG12-ATG3 protein-protein interaction involved in autophagy, demonstrating potential as a therapeutic drug for autophagy-dependent tumors and inflammation. [Read the Full Post]

Sirtuin 1 activator alleviated lethal inflammatory injury via promotion of autophagic degradation of pyruvate kinase M2

75 views | Jun 29 2023

The present study demonstrated that activation of SIRT1 through treatment with SRT2104 promotes autophagic degradation of pyruvate kinase M2 (PKM2), leading to reduced inflammation, improved organ function, and increased survival in lethal endotoxemia [Read the Full Post]

The pattern of histone H3 epigenetic posttranslational modifications is regulated by the VRK1 chromatin kinase

57 views | Jun 29 2023

The chromatin kinase VRK1 regulates the epigenetic patterns of histone H3 acetylation and methylation, particularly at lysines 4, 9, and 27, and is essential for coordinating chromatin organization and nuclear functions. [Read the Full Post]

LSD1 inhibitors for cancer treatment: Focus on multi-target agents and compounds in clinical trials

0 views | Jun 29 2023

This review summarizes the structure and functions of LSD1, its role in cancer and non-cancer diseases, and the potential of covalent and non-covalent LSD1 inhibitors, including those in clinical trials, as potent and selective anticancer agents. [Read the Full Post]

Rapid adaptation to CDK2 inhibition exposes intrinsic cell-cycle plasticity

43 views | Jun 29 2023

Co-inhibition of CDK2 and CDK4/6 may be required to suppress adaptation to CDK2 inhibitors and effectively target the proliferative program in cancer cells. [Read the Full Post]

Runx3-overexpression cooperates with ex vivo AKT inhibition to generate receptor-engineered T cells with better persistence, tumor-residency, and antitumor ability

110 views | Jun 28 2023

Combining Runx3 overexpression with ex vivo AKT inhibition generates CAR-T cells with both tissue-resident and central memory characteristics, enhancing their persistence, cytotoxic potential, and tumor-residency ability for the treatment of solid tumors. [Read the Full Post]

Charting the Chemical Reaction Space around a Multicomponent Combination: Controlled Access to a Diverse Set of Biologically Relevant Scaffolds

21 views | Jun 28 2023

Researchers have developed general protocols to selectively access desired chemotypes by combining carbonyls, amines, and isocyanoacetates, leading to the synthesis of unsaturated imidazolone scaffolds with the chromophore of the green fluorescent protein and the core structure of the natural product coelenterazine, as well as unprecedented reactivity at the C-2 position to obtain diverse derivatives featuring natural products, kinase inhibitors, and fluorescent probes. [Read the Full Post]

Anna Karenina principle in personalized treatment of bladder cancer according to oncogram: which drug for which patient?

29 views | Jun 28 2023

The ex vivo application of chemotherapy, immunotherapy, and targeted agents using the oncogram method showed higher good response rates compared to the control group in bladder cancer patients, with variations observed on a per-patient basis. [Read the Full Post]

Erlotinib-Loaded Dendrimer Nanocomposites as a Targeted Lung Cancer Chemotherapy

37 views | Jun 28 2023

The study found that the cationic G4 PAMAM dendrimer formulation of erlotinib showed superior antiproliferative activity against A549 lung cells compared to neutral G5 dendrimers and erlotinib alone, suggesting its potential as a targeted and sustained-release carrier for lung cancer treatment. [Read the Full Post]

Extraordinary clinical response to ibrutinib in low-grade ovarian cancer guided by organoid drug testing

87 views | Jun 28 2023

This case study showcases the efficacy of ex vivo drug testing using patient-derived tumor organoids as a precision medicine approach, leading to significant clinical improvement and prolonged stable disease in a patient with platinum-resistant, advanced low-grade serous ovarian cancer. [Read the Full Post]

Cabotegravir (Apretude) for Pre-exposure Prophylaxis for HIV Type 1 Infection

25 views | Jun 27 2023

Cabotegravir (Apretude) is an extended-release injectable HIV-1 antiretroviral medication used as pre-exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV-1 infection in HIV-negative individuals at high risk. [Read the Full Post]

DHA induces adipocyte lipolysis through endoplasmic reticulum stress and the cAMP/PKA signaling pathway in grass carp ( Ctenopharyngodon idella)

82 views | Jun 27 2023

The study demonstrated that supplementation of docosahexaenoic acid (DHA) in grass carp induced lipolysis by evoking endoplasmic reticulum (ER) stress, activating the cAMP/PKA signaling pathway, and involving components of the unfolded protein response, providing insights into mitigating lipid accumulation in fish through DHA targeting. [Read the Full Post]

Synthesis and Preclinical Positron Emission Tomography Imaging of the p38 MAPK Inhibitor [11C]Talmapimod: Effects of Drug Efflux and Sex Differences

39 views | Jun 27 2023

The development of the first positron emission tomography (PET) radiotracer for imaging MAPK p38α/β, synthesized through radiolabeling the inhibitor talmapimod with carbon-11, showed promising results but faced challenges regarding its non-displaceable binding and P-gp efflux. [Read the Full Post]

Characterization of Potent ABCG2 Inhibitor Derived from Chromone: From the Mechanism of Inhibition to Human Extracellular Vesicles for Drug Delivery

46 views | Jun 27 2023

This study characterizes a potent ABCG2 inhibitor, C4a, and demonstrates its selectivity and efficacy in inhibiting ABCG2-mediated drug efflux, utilizing liposomes and extracellular vesicles for improved delivery and highlighting the potential of plasma circulating EVs as a drug delivery system for hydrophobic drugs targeting membrane proteins. [Read the Full Post]

Celastrol inhibits necroptosis by attenuating the RIPK1/RIPK3/MLKL pathway and confers protection against acute pancreatitis in mice

0 views | Jun 27 2023

Celastrol demonstrates potential as a therapeutic agent for inhibiting necroptosis and reducing the severity of necroptotic-related diseases such as pancreatitis [Read the Full Post]

Deciphering the mechanism of PSORI-CM02 in suppressing keratinocyte proliferation through the mTOR/HK2/glycolysis axis

65 views | Jun 26 2023

PSORI-CM02 exhibits anti-proliferative effects on psoriatic keratinocytes by inhibiting the mTOR/HK2/glycolysis axis, as demonstrated in both in vitro and in vivo models. [Read the Full Post]