In Silico Screening Identifies a Novel Potential PARP1 Inhibitor Targeting Synthetic Lethality in Cancer Treatment
Synthetic lethality describes situations in which defects in two different genes or pathways together result in cell death. This concept has been applied to drug development for cancer treatment, as represented by Poly (ADP-ribose) polymerase (PARPs) inhibitors. In the current study, we performed a...
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MDPI AG
2016-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | http://www.mdpi.com/1422-0067/17/2/258 |
| _version_ | 1811228899111075840 |
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| author | Jian Li Nan Zhou Peiling Cai Jinku Bao |
| author_facet | Jian Li Nan Zhou Peiling Cai Jinku Bao |
| author_sort | Jian Li |
| collection | DOAJ |
| description | Synthetic lethality describes situations in which defects in two different genes or pathways together result in cell death. This concept has been applied to drug development for cancer treatment, as represented by Poly (ADP-ribose) polymerase (PARPs) inhibitors. In the current study, we performed a computational screening to discover new PARP inhibitors. Among the 11,247 compounds analyzed, one natural product, ZINC67913374, stood out by its superior performance in the simulation analyses. Compared with the FDA approved PARP1 inhibitor, olaparib, our results demonstrated that the ZINC67913374 compound achieved a better grid score (−86.8) and amber score (−51.42). Molecular dynamics simulations suggested that the PARP1-ZINC67913374 complex was more stable than olaparib. The binding free energy for ZINC67913374 was −177.28 kJ/mol while that of olaparib was −159.16 kJ/mol. These results indicated ZINC67913374 bound to PARP1 with a higher affinity, which suggest ZINC67913374 has promising potential for cancer drug development. |
| first_indexed | 2024-04-12T10:05:19Z |
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| issn | 1422-0067 |
| language | English |
| last_indexed | 2024-04-12T10:05:19Z |
| publishDate | 2016-02-01 |
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| spelling | doaj.art-6921e76d53e9472893585adf60f4ccdd2022-12-22T03:37:28ZengMDPI AGInternational Journal of Molecular Sciences1422-00672016-02-0117225810.3390/ijms17020258ijms17020258In Silico Screening Identifies a Novel Potential PARP1 Inhibitor Targeting Synthetic Lethality in Cancer TreatmentJian Li0Nan Zhou1Peiling Cai2Jinku Bao3School of Medicine, Chengdu University, Chengdu 610106, ChinaCollege of Life Sciences and Key Laboratory for Bio-Resources of Ministry of Education, Sichuan University, Chengdu 610064, ChinaSchool of Medicine, Chengdu University, Chengdu 610106, ChinaCollege of Life Sciences and Key Laboratory for Bio-Resources of Ministry of Education, Sichuan University, Chengdu 610064, ChinaSynthetic lethality describes situations in which defects in two different genes or pathways together result in cell death. This concept has been applied to drug development for cancer treatment, as represented by Poly (ADP-ribose) polymerase (PARPs) inhibitors. In the current study, we performed a computational screening to discover new PARP inhibitors. Among the 11,247 compounds analyzed, one natural product, ZINC67913374, stood out by its superior performance in the simulation analyses. Compared with the FDA approved PARP1 inhibitor, olaparib, our results demonstrated that the ZINC67913374 compound achieved a better grid score (−86.8) and amber score (−51.42). Molecular dynamics simulations suggested that the PARP1-ZINC67913374 complex was more stable than olaparib. The binding free energy for ZINC67913374 was −177.28 kJ/mol while that of olaparib was −159.16 kJ/mol. These results indicated ZINC67913374 bound to PARP1 with a higher affinity, which suggest ZINC67913374 has promising potential for cancer drug development.http://www.mdpi.com/1422-0067/17/2/258synthetic lethalityPARP inhibitorDNA damage response (DDR) |
| spellingShingle | Jian Li Nan Zhou Peiling Cai Jinku Bao In Silico Screening Identifies a Novel Potential PARP1 Inhibitor Targeting Synthetic Lethality in Cancer Treatment International Journal of Molecular Sciences synthetic lethality PARP inhibitor DNA damage response (DDR) |
| title | In Silico Screening Identifies a Novel Potential PARP1 Inhibitor Targeting Synthetic Lethality in Cancer Treatment |
| title_full | In Silico Screening Identifies a Novel Potential PARP1 Inhibitor Targeting Synthetic Lethality in Cancer Treatment |
| title_fullStr | In Silico Screening Identifies a Novel Potential PARP1 Inhibitor Targeting Synthetic Lethality in Cancer Treatment |
| title_full_unstemmed | In Silico Screening Identifies a Novel Potential PARP1 Inhibitor Targeting Synthetic Lethality in Cancer Treatment |
| title_short | In Silico Screening Identifies a Novel Potential PARP1 Inhibitor Targeting Synthetic Lethality in Cancer Treatment |
| title_sort | in silico screening identifies a novel potential parp1 inhibitor targeting synthetic lethality in cancer treatment |
| topic | synthetic lethality PARP inhibitor DNA damage response (DDR) |
| url | http://www.mdpi.com/1422-0067/17/2/258 |
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