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INNOSC Theranostics and
Pharmacological Sciences PI3K-α inhibitors for cancer immunotherapy

refined to improve the quality, accuracy, consistency, Ethics approval and consent to participate
and completeness of the data while reducing noise,
errors, outliers, and inconsistencies. A virtual screening Not applicable.
workflow coupled with molecular docking evaluated Consent for publication
the binding potentials of the refined ligands within the
binding pocket 6PYS. Furthermore, the field-based QSAR Not applicable.
technique elucidated the potential interactions between
the ligands and probe atoms having specific attributes Availability of data
such as hydrophobic, electrostatic, hydrogen bond donor, Python codes for data preprocessing are available on
or acceptor at each point in a 3D grid, highlighting key request.
features influencing ligand activity, potency, and selectivity
within the target binding site. In addition, the field-based References
QSAR model captured the shape, size, and flexibility 1. Toppmeyer DL, Press MF. Testing considerations for
of the ligands, along with their complementarity with phosphatidylinositol-3-kinase catalytic subunit Alpha as an
the target. Multivariate PLS regression was employed to emerging biomarker in advanced breast cancer. Cancer Med.
evaluate the relationship between the ligand molecular 2020;9:6463-6472.
fields (independent variables) and the biological activity doi: 10.1002/cam4.3278
(dependent variable). Four PLS factors revealed important
information from the data, indicating the influence of 2. Mansour MA, Lasheen DS, Gaber HM, Abouzid KAM.
Elaborating piperazinyl-furopyrimidine based scaffolds as
variance from the data on the 3D-QSAR model. A rational phosphoinositol-3-kinase enzyme alpha (PI3Kα) inhibitors to
drug design approach was employed to design a molecule combat pancreatic cancer. RSC Adv. 2020;10(53):32103-32112.
that could bind to the target and modulate its functions.
The clinical relevance and ADMET properties of the newly doi: 10.1039/D0RA06428A
designed molecule were predicted and evaluated according 3. Castillo JJ, Furman M, Winer ES. CAL-101:
to recognized standards, including Lipinski’s rule of five A phosphatidylinositol-3-kinase p110-delta inhibitor for the
and Jorgensen’s rule of three. Overall, the study proposes treatment of lymphoid malignancies. Expert Opin Investig
the use of advanced and reliable computational techniques Drugs. 2012;21:15-22.
to design novel and potent inhibitors of PI3K-α, a doi: 10.1517/13543784.2012.640318
potential target for cancer immunotherapy, along with the 4. Akinleye A, Avvaru P, Furqan M, Song Y, Liu D.
repurposing of existing drugs for new indications. Phosphatidylinositol 3-kinase (PI3K) inhibitors as cancer
Acknowledgments therapeutics. J Hematol Oncol. 2013;6:88.
doi: 10.1186/1756-8722-6-88
None.
5. Burris HA. Overcoming acquired resistance to anticancer
Funding therapy: Focus on the PI3K/AKT/mTOR pathway. Cancer
Chemother Pharmacol. 2013;71:829-842.
None.
doi: 10.1007/s00280-012-2043-3
Conflict of interest 6. Popova NV, Jücker M. The role of mTOR signaling as a
The authors declare that they have no competing interests. therapeutic target in cancer. Int J Mol Sci. 2021;22(4):1743.
doi: 10.3390/ijms22041743
Author contributions
7. Liu P, Cheng H, Roberts TM, Zhao JJ. Targeting the
Conceptualization: Kevin Tochukwu Dibia, Sandra Nneka phosphoinositide 3-kinase pathway in cancer. Nat Rev Drug
Van-Dibia Discov. 2009;8(8):627-644.
Data curation: Kevin Tochukwu Dibia doi: 10.1038/nrd2926
Formal Analysis: Kevin Tochukwu Dibia
Investigation: Kevin Tochukwu Dibia, Sandra Nneka Van- 8. Saal LH, Johansson P, Holm K, et al. Poor prognosis in
carcinoma is associated with a gene expression signature
Dibia, Philomena Kanwulia Igbokwe of aberrant PTEN tumor suppressor pathway activity. Proc
Methodology: Kevin Tochukwu Dibia Natl Acad Sci U S A. 2007;104(18):7564-7569.
Writing—Original Draft: Kevin Tochukwu Dibia
Writing—Review & Editing: Kevin Tochukwu Dibia, doi: 10.1073/pnas.0702507104
Sandra Nneka Van-Dibia 9. Millis SZ, Ikeda S, Reddy S, Gatalica Z, Kurzrock R.

Volume 7 Issue 2 (2024) 22 doi: 10.36922/itps.2340