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Pulmonary tumor thrombotic microangiopathy (PTTM) is an underrecognized cause of pulmonary hypertension and fulminant right ventricle failure. It is associated with a high mortality due to delay in diagnosis. We present two cases of PTTM, both diagnosed postmortem, highlighting the importance of timely identification and initiation of treatment for this nearfatal condition. [ABSTRACT FROM AUTHOR]

Cyclin‐dependent protein kinases (CDKs) are serine/threonine kinases of the CMGC family. The cyclin D/CDK4 complex plays an important role in cell proliferation. Deregulation of the CDK4‐cyclin D pathway leads to uncontrolled cell proliferation, causing various tumors and cancers in humans. CDK4 overexpression is widely observed in colorectal and uterine cervical carcinomas, liposarcomas, osteosarcomas, and breast cancer. CDK4 is extensively studied as a therapeutic target in breast cancer. Hence, the identification of the binding modes of inhibitors and important active‐site residues is crucial. However, an experimentally determined crystal structure of ligand‐bound CDK4 kinase has not been reported to date. Thus, this study aimed to identify hotspot residues in the ligand‐binding interface of CDK4. Three compounds exhibiting very high inhibitory activity against CDK4 (Cpd03, Cpd13, and Cpd14) were selected as potent antagonists in this study. Molecular docking and molecular dynamics simulation were carried out to identify the binding modes and crucial residues. For validation, we calculated total binding free energy and energy decomposition, which identified residues Ala151, Ala30, Asp152, His89, Ile9, Leu141, Phe87, Val17, and Val90 are the highest‐energy contributors important for inhibitor binding. The results of our study provide insights in the binding patterns of CDK4 inhibitors and reveal key residues in the ligand‐binding interface. [ABSTRACT FROM AUTHOR]

A RET (Rearranged during transfection) kinase belongs to a receptor tyrosine kinase family. It plays a major role in development, maturation, survival, and maintenance of cells and tissues. Oncogenic activation of RET has been reported in numerous cancers. Thus, it is a significant therapeutic target for cancer. Present work covers docking and 3D‐QSAR techniques executed on anilinoquinazoline derivatives as RET kinase antagonists. Docking study recognized important active site amino acid residues like Leu730, Gly731, Gly733, Glu734, Ala807, Gly810, Ser811, and Asp874 which inhibits the RET kinase. In 3D‐QSAR technique, receptor‐guided CoMFA (q2 = 0.723, NOC = 5, r2 = 0.980) as well as CoMSIA (q2 = 0.767, NOC = 6, r2 = 0.967) models were produced. The stabilities of these models were evaluated using diverse validation techniques. Contour maps showed that steric and hydrogen bond donor substitutions are favored at R1 and R2 positions whereas positive and negative substitutions are favored at the R1 position to enhance the potency. In addition, the substitution of H‐bond accepting group to the region which is close to both phenyl and piperazine is favored. Hence, the outcome of this study could be beneficial to design more potent inhibitors for RET kinase. [ABSTRACT FROM AUTHOR]