THE MOLECULAR INTERACTION AND ADMET PREDICTION OF MODIFIED JPH203 AS A POTENTIAL RADIOPHARMACEUTICAL KIT FOR MOLECULAR IMAGING OF CANCER: AN IN SILICO RESEARCH

Authors

  • HOLIS ABDUL HOLIK Department of Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy/Universitas Padjadjaran, Sumedang 45363, (West Java) Indonesia
  • FAISAL MAULANA IBRAHIM Department of Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy/Universitas Padjadjaran, Sumedang 45363, (West Java) Indonesia
  • ELISHA WIANATALIE Department of Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy/Universitas Padjadjaran, Sumedang 45363, (West Java) Indonesia
  • ARIFUDIN ACHMAD Department of Nuclear Medicine, Faculty of Medicine/Universitas Padjadjaran, Sumedang 45363, (West Java) Indonesia
  • AHMAD FARIED Department of Nuclear Medicine, Faculty of Medicine/Universitas Padjadjaran, Sumedang 45363, (West Java) Indonesia
  • ACHMAD HUSSEIN SUNDAWA KARTAMIHARDJA Department of Nuclear Medicine, Faculty of Medicine/Universitas Padjadjaran, Sumedang 45363, (West Java) Indonesia

DOI:

https://doi.org/10.22159/ijap.2021.v13s4.43860

Keywords:

JPH203, LAT-1, Molecular docking, ADMET, In silico

Abstract

Objective: In this study, various types of pharmacokinetic modifying linkers and chelators are combined with JPH203 to obtain the best-docked molecule for prospective radiopharmaceutical kits.

Methods: AutoDock 4.2.6 and AutoDockTools 1.5.6 programs was used to do the molecular docking simulation and ADMET prediction was done using VNN-ADMET to predict the pharmacokinetics and toxicity of the ligand.

Results: The result of this study showed that JPH203-linker K-NOTA has the best affinity with a docking score of about-10.7 kcal/mol and shows hydrogen interaction with Tyr259, which acts as key residue of the active site.

Conclusion: Based on the results, JPH203-linker K-NOTA has good potential as a radiopharmaceutical kit of cancer.

Downloads

Download data is not yet available.

References

Noncommunicable diseases. Available from: https://www.who.int/news-room/fact-sheets/detail/noncommunicable-diseases. [Last accessed on 20 Jul 2020].

Blackadar CB. Historical review of the causes of cancer. World J Clin Oncol. 2016;7(1):54-86. doi: 10.5306/wjco.v7.i1.54, PMID 26862491.

Bright CJ, Reulen RC, Winter DL, Stark DP, McCabe MG, Edgar AB, Frobisher C, Hawkins MM. Risk of subsequent primary neoplasms in survivors of adolescent and young adult cancer (Teenage and Young Adult Cancer Survivor Study): a population-based, cohort study. Lancet Oncol. 2019;20(4):531-45. doi: 10.1016/S1470-2045(18)30903-3, PMID 30797674.

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394-424. doi: 10.3322/caac.21492, PMID 30207593.

Choi DW, Kim DK, Kanai Y, Wempe MF, Endou H, Kim JK. JPH203, a selective L-type amino acid transporter 1 inhibitor, induces mitochondria-dependent apoptosis in Saos2 human osteosarcoma cells. Korean J Physiol Pharmacol. 2017;21(6):599-607. doi: 10.4196/kjpp.2017.21.6.599, PMID 29200902.

Scalise M, Galluccio M, Console L, Pochini L, Indiveri C. The human SLC7A5 (LAT1): the intriguing histidine/large neutral amino acid transporter and its relevance to human health. Front Chem. 2018;6:243. doi: 10.3389/fchem.2018.00243, PMID 29988369.

Achmad A, Lestari S, Holik HA, Rahayu D, Bashari MH, Faried A, Kartamihardja AHS. Highly specific l-type amino acid transporter 1 inhibition by JPH203 as a potential pan-cancer treatment. Processes. 2021;9(7):1170. doi: 10.3390/ pr9071170.

Hayashi K, Jutabha P, Maeda S, Supak Y, Ouchi M, Endou H, Fujita T, Chida M, Anzai N. LAT1 acts as a crucial transporter of amino acids in human thymic carcinoma cells. J Pharmacol Sci. 2016 Nov;132(3):201-4. doi: 10.1016/j.jphs.2016.07.006, PMID 27567475.

Oda K, Hosoda N, Endo H, Saito K, Tsujihara K, Yamamura M, Sakata T, Anzai N, Wempe MF, Kanai Y, Endou H. L-type amino acid transporter 1 inhibitors inhibit tumor cell growth. Cancer Sci. 2010 Jan;101(1):173-9. doi: 10.1111/j.1349-7006.2009.01386.x, PMID 19900191.

Sarko D, Eisenhut M, Haberkorn U, Mier W. Bifunctional chelators in the design and application of radiopharmaceuticals for oncological diseases. Curr Med Chem. 2012;19(17):2667-88. doi: 10.2174/092986712800609751, PMID 22455579.

Liu S. Bifunctional coupling agents for radiolabeling of biomolecules and target-specific delivery of metallic radionuclides. Adv Drug Deliv Rev. 2008 Sep;60(12):1347-70. doi: 10.1016/j.addr.2008.04.006, PMID 18538888.

Ibrahim FM, Holik HA, Achmad A. In silico studies of amentoflavone and its derivatives against SARS-COV-2. Rasayan J Chem. 2021;14(3):1469-81.

Hidayat S, Ibrahim FM, Pratama KF, Muchtaridi M. The interaction of alpha mangostin and its derivatives against main protease enzyme in COVID 19 using in silico methods. J Adv Pharm Technol Res. 2021;12(3):285-90.

Patrick S, Lui R, Valmik Desai AW. Illqvist, vNN web server for ADMET predictions. Front Pharmacol. 2017;8(889).

Yan R, Zhao X, Lei J, Zhou Q. Structure of the human LAT1-4F2hc heteromeric amino acid transporter complex. Nature. 2019;568(7750):127-30. doi: 10.1038/s41586-019-1011-z, PMID 30867591.

Jeffrey GA. An introduction to hydrogen bonding. England: Oxford University Press. England; 1997.

Published

11-12-2021

How to Cite

HOLIK, H. A., IBRAHIM, F. M., WIANATALIE, . E., ACHMAD, A., FARIED, A., & KARTAMIHARDJA, A. H. S. (2021). THE MOLECULAR INTERACTION AND ADMET PREDICTION OF MODIFIED JPH203 AS A POTENTIAL RADIOPHARMACEUTICAL KIT FOR MOLECULAR IMAGING OF CANCER: AN IN SILICO RESEARCH. International Journal of Applied Pharmaceutics, 13(4), 205–209. https://doi.org/10.22159/ijap.2021.v13s4.43860

Issue

Section

Original Article(s)