PMID- 37139547
OWN - NLM
STAT- MEDLINE
DCOM- 20240311
LR  - 20240328
IS  - 1538-0254 (Electronic)
IS  - 0739-1102 (Linking)
VI  - 42
IP  - 5
DP  - 2024 Mar
TI  - In-silico identification of novel DDI2 inhibitor in glioblastoma via repurposing 
      FDA approved drugs using molecular docking and MD simulation study.
PG  - 2270-2281
LID - 10.1080/07391102.2023.2204371 [doi]
AB  - Glioblastoma, the most severe form of brain tumor and a leading cause of death 
      within a year of diagnosis, is characterized by excessive protein synthesis and 
      folding in the lumen of the endoplasmic reticulum (ER), leading to increased ER 
      stress in the cells of GBM tissues. To mitigate this stress the cancer cells have 
      intelligently adopted a plethora of response mechanisms and Unfolded Protein 
      Response (UPR) is one of those. To bear with this exhaustive situation cells 
      upregulate a strong protein degradation system in form of 26S proteasome and 
      blocking of proteasomal gene synthesis may be a potential therapeutic action 
      against GBM. Proteasomal gene synthesis is exclusively dependent on the 
      transcription factor Nuclear respiratory factor 1 (NRF1) and its activating 
      enzyme DNA damage inducible 1 homolog 2 (DDI2). Here in this study, we performed 
      molecular docking against DDI2 with the 20 FDA-approved drugs and identified 
      Alvimopan and Levocabastine as the top two compounds with the best binding score 
      along with the standard drug Nelfinavir. MD simulation (100 ns) of these 
      protein-ligand docked complexes reveals that the stability and compactness of 
      Alvimopan are high in comparison with Nelfinavir. Our in-silico (Molecular 
      docking and Molecular dynamics simulation) studies pointed out that Alvimopan may 
      be repurposed as a DDI2 inhibitor and can be used as a potential anticancer agent 
      for the treatment of brain tumors.Communicated by Ramaswamy H. Sarma.
FAU - Roy, Pritam Kumar
AU  - Roy PK
AD  - School of Medical Science and Technology, Indian Institute of Technology, 
      Kharagpur, West Bengal, India.
FAU - Majumder, Ranabir
AU  - Majumder R
AUID- ORCID: 0000-0003-3585-3276
AD  - School of Medical Science and Technology, Indian Institute of Technology, 
      Kharagpur, West Bengal, India.
FAU - Mandal, Mahitosh
AU  - Mandal M
AD  - School of Medical Science and Technology, Indian Institute of Technology, 
      Kharagpur, West Bengal, India.
LA  - eng
PT  - Journal Article
DEP - 20230503
PL  - England
TA  - J Biomol Struct Dyn
JT  - Journal of biomolecular structure & dynamics
JID - 8404176
RN  - 0 (Antineoplastic Agents)
RN  - HO3OGH5D7I (Nelfinavir)
RN  - EC 3.4.- (DDI2 protein, human)
RN  - EC 3.4.- (Aspartic Acid Proteases)
SB  - IM
MH  - Humans
MH  - *Antineoplastic Agents/pharmacology/therapeutic use
MH  - Drug Repositioning
MH  - *Glioblastoma/drug therapy
MH  - Molecular Docking Simulation
MH  - Molecular Dynamics Simulation
MH  - Nelfinavir/pharmacology
MH  - *Aspartic Acid Proteases/antagonists & inhibitors
OTO - NOTNLM
OT  - Aspartyl protease
OT  - DDI2
OT  - NRF1
OT  - glioblastoma (GBM)
OT  - molecular docking and MD simulation
OT  - proteasome
EDAT- 2023/05/04 06:42
MHDA- 2024/03/11 06:43
CRDT- 2023/05/04 02:22
PHST- 2024/03/11 06:43 [medline]
PHST- 2023/05/04 06:42 [pubmed]
PHST- 2023/05/04 02:22 [entrez]
AID - 10.1080/07391102.2023.2204371 [doi]
PST - ppublish
SO  - J Biomol Struct Dyn. 2024 Mar;42(5):2270-2281. doi: 
      10.1080/07391102.2023.2204371. Epub 2023 May 3.