Importance of Solvents’ Translational–Rotational Coupling for Translational Jump of a Small Hydrophobic Solute in Supercooled Water

2018 ◽  
Vol 122 (30) ◽  
pp. 7569-7583 ◽  
Author(s):  
Vikas Dubey ◽  
Nitesh Kumar ◽  
Snehasis Daschakraborty
Keyword(s):  
Supercooled Water ◽  
Hydrophobic Solute ◽  
Small Hydrophobic ◽  
Rotational Coupling

Single particle dynamics of supercooled water and the kinetic glass transition

1998 ◽  
Vol 08 (PR6) ◽  
pp. Pr6-109-Pr6-113
Author(s):  
P. Gallo ◽  
F. Sciortino ◽  
P. Tartaglia ◽  
S.-H. Chen
Keyword(s):  
Glass Transition ◽  
Single Particle ◽  
Supercooled Water ◽  
Particle Dynamics

IMPROVED LUMPED-DIFFERENTIAL ANALYSIS OF THE FREEZING PROCESS IN A SUPERCOOLED WATER DROPLET

2020 ◽  
Author(s):  
Emerson Barbosa dos Anjos ◽  
Carolina Palma Naveira Cotta ◽  
Renato Machado Cotta ◽  
Igor Soares Carvalho ◽  
Manish Tiwari
Keyword(s):  
Water Droplet ◽  
Supercooled Water ◽  
Freezing Process ◽  
Differential Analysis

Targeting p53-MDM2 Interaction Using Small Molecule Inhibitors and the Challenges Needed to be Addressed

2019 ◽  
Vol 20 (11) ◽  
pp. 1091-1111 ◽  
Author(s):  
Maryam Zanjirband ◽  
Soheila Rahgozar
Keyword(s):  
Clinical Trials ◽  
Small Molecule ◽  
Small Molecule Inhibitors ◽  
Tp53 Gene ◽  
Therapeutic Agents ◽  
Negative Regulator ◽  
Mdm2 Protein ◽  
Independent Effects ◽  
Small Hydrophobic ◽  
Targeted Therapeutic

MDM2 protein is the core negative regulator of p53 that maintains the cellular levels of p53 at a low level in normal cells. Mutation of the TP53 gene accounts for 50% of all human cancers. In the remaining malignancies with wild-type TP53, p53 function is inhibited through other mechanisms. Recently, synthetic small molecule inhibitors have been developed which target a small hydrophobic pocket on MDM2 to which p53 normally binds. Given that MDM2-p53 antagonists have been undergoing clinical trials for different types of cancer, this review illustrates different aspects of these new cancer targeted therapeutic agents with the focus on the major advances in the field. It emphasizes on the p53 function, regulation of p53, targeting of the p53-MDM2 interaction for cancer therapy, and p53-dependent and -independent effects of inhibition of p53-MDM2 interaction. Then, representatives of small molecule MDM2-p53 binding antagonists are introduced with a focus on those entered into clinical trials. Furthermore, the review discusses the gene signatures in order to predict sensitivity to MDM2 antagonists, potential side effects and the reasons for the observed hematotoxicity, mechanisms of resistance to these drugs, their evaluation as monotherapy or in combination with conventional chemotherapy or with other targeted therapeutic agents. Finally, it highlights the certainly intriguing questions and challenges which would be addressed in future studies.

scholarly journals An Effective and Safe Enkephalin Analog for Antinociception

Pharmaceutics ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 927
Author(s):  
KK DurgaRao Viswanadham ◽  
Roland Böttger ◽  
Lukas Hohenwarter ◽  
Anne Nguyen ◽  
Elham Rouhollahi ◽  
...  
Keyword(s):  
Physical Dependence ◽  
Opioid Peptide ◽  
Vehicle Group ◽  
Endogenous Opioid ◽  
Endogenous Opioid Peptide ◽  
Extended Plasma ◽  
The Central Nervous System ◽  
Overdose Deaths ◽  
Plasma Half Life ◽  
Small Hydrophobic

Opioids account for 69,000 overdose deaths per annum worldwide and cause serious side effects. Safer analgesics are urgently needed. The endogenous opioid peptide Leu-Enkephalin (Leu-ENK) is ineffective when introduced peripherally due to poor stability and limited membrane permeability. We developed a focused library of Leu-ENK analogs containing small hydrophobic modifications. N-pivaloyl analog KK-103 showed the highest binding affinity to the delta opioid receptor (68% relative to Leu-ENK) and an extended plasma half-life of 37 h. In the murine hot-plate model, subcutaneous KK-103 showed 10-fold improved anticonception (142%MPE·h) compared to Leu-ENK (14%MPE·h). In the formalin model, KK-103 reduced the licking and biting time to ~50% relative to the vehicle group. KK-103 was shown to act through the opioid receptors in the central nervous system. In contrast to morphine, KK-103 was longer-lasting and did not induce breathing depression, physical dependence, and tolerance, showing potential as a safe and effective analgesic.

Possible Anomaly in the Surface Tension of Supercooled Water: New Experiments at Extreme Supercooling down to −31.4 °C

2020 ◽  
Vol 11 (11) ◽  
pp. 4443-4447 ◽  
Author(s):  
Václav Vinš ◽  
Jiří Hykl ◽  
Jan Hrubý ◽  
Aleš Blahut ◽  
David Celný ◽  
...  
Keyword(s):  
Surface Tension ◽  
Supercooled Water

Supercooled Water Drops Do Not Freeze During Impact on Hybrid Janus Particle-Based Surfaces

2018 ◽  
Vol 31 (1) ◽  
pp. 112-123 ◽  
Author(s):  
Madeleine Schwarzer ◽  
Thomas Otto ◽  
Markus Schremb ◽  
Claudia Marschelke ◽  
Hisaschi T. Tee ◽  
...  
Keyword(s):  
Supercooled Water ◽  
Janus Particle ◽  
Water Drops
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