Random Records

Note for: PARP1 Inhibitors: antitumor drug design_2014 PMID: 26483957 Overview PARP1 -        common nuclear protein (1-2 million molecules/cells) -        sensor for DNA strand breaks -        highly expression of PARP1 can be found in some cancers, treatment-resistance of tumors -        act as chemotherapy and radio-sensitizer -        focus on properties and feature of PARP1 inhibitors: clinical and preclinical levels -        discuss on problems -- > application of PARP1 inhibitors, possibility of developing new PARP1 inhibitors -- > aim at DNA binding and transcriptional activity rather than catalytic domain Introduction -        DNA break o    PARP1 recognize through Zn-finger o    Transferring ADP-ribose to related protein as well as PARP1 §   Downstream effect ·          Chromatin decondensation o    Removing H1 linker histone ·          Recruiting repair enzyme -        Three levels of damage o    Mild damage -- > activation of P

Note for: Advances and perspectives of PARP inhibitors Doi: 10.1186/s40164-019-0154-9 Overview: -           Continuous DNA replication in cancer cells leads to higher demand of DNA repair components -           Growing evidence -- > broader population of patients -- > benefit from PARPi beside one who has BRCA1/2 mutated tumors -           Potential patients for PARPi o    Defective in replication stress o    HR deficiency -           Summarizing o    Advanced of PARPi in clinical application o    PARPi based combination strategies in preclinical and clinical studies Cancer characteristic -           Generation of mutations -           Neoantigens -           Genome integrity To survive -           Maintain specific DNA damage repair pathways to control DNA damage events -           Thus, targeting DNA repair pathways -- > ideal targets for cancer treatment Rational -           Different of HR status between cancer (HR-defective) and norma

Note for: PPIMpred: a web server for high-throughput screening of small molecules targeting protein-protein interaction Doi: 10.1098/rsos.160501 Overall concept: PPIMpred -           web server for high throughput screening of small molecules -           targeting protein-protein interaction o    MDM2-p53 o    Bcl2-Bak o    cMyc-Max -           Method for machine learning o    3 different kernels of support vector machine §   Linear §   Polynomial §   Radial basis o    Naïve Byes o    Random forest -           5 folds cross validation is used to validate the model Three protein-protein interactions model -- > screen in large dataset 265,242 small chemical from NCI Enable user to get the structural + chemical similarities with known chemical modulator   Introduction: -           Small chemicals -- > inhibit PPI at the interfaces -- > PPI modulators o    Small amounts of PPI modulators enter clinical trial §   Nutlin-3a (Mdm2/P53)