Wikipedia

Eganelisib

Eganelisib (USAN), codenamed IPI-549, is an experimental drug being investigated as a possible treatment for cancer. It is a highly selective phosphoinositide 3-kinase inhibitor, and thus works by inhibiting the enzyme PIK3CG, disrupting the PI3K/AKT/mTOR signaling pathway which plays important roles in the development of cancer.[1]

Eganelisib
Clinical data
Routes of
administration		Oral
ATC code
  • None
Identifiers
  • 2-amino-N-[(1S)-1-{8-[(1-methyl-1H-pyrazol-4-yl)ethynyl]-1-oxo-2-phenyl-1,2-dihydroisoquinolin-3-yl}ethyl]pyrazolo[1,5-a]pyrimidine-3-carboxamide
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
ChEMBL
PDB ligand
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC30H24N8O2
Molar mass528.576 g·mol−1
3D model (JSmol)
  • Cn1cc(cn1)C#Cc6cccc2c6C(=O)N(C(=C2)C(C)NC(=O)c4c3ncccn3nc4N)c5ccccc5
  • InChI=1S/C30H24N8O2/c1-19(34-29(39)26-27(31)35-37-15-7-14-32-28(26)37)24-16-22-9-6-8-21(13-12-20-17-33-36(2)18-20)25(22)30(40)38(24)23-10-4-3-5-11-23/h3-11,14-19H,1-2H3,(H2,31,35)(H,34,39)/t19-/m0/s1
  • Key:XUMALORDVCFWKV-IBGZPJMESA-N

Eganelisib is being developed by Infinity Pharmaceuticals. Early clinical trial results were published in September 2016.[2] On September 29, 2020, it was granted Fast Track designation by the United States Food and Drug Administration (FDA) as a treatment for inoperable, locally advanced, or metastatic triple-negative breast cancer, combined with a checkpoint inhibitor and chemotherapy.[3]

As of October 2020, five phase I/II clinical trials were ongoing in the United States, and one in Europe.[4]

Eganelisib has also been explored for its potential use in the treatment of COVID-19 and MRSA. Early, pre-clinical in vitro studies published in 2024 suggested eganelisib's ability to inhibit PI3Kγ, an enzyme involved in myeloid cell movement into infected tissues, could reduce excessive immune system activity that can damage tissues. By inhibiting PI3Kγ, eganelisib may prevent myeloid cells from entering and damaging tissue in patients with COVID-19 or MRSA, thereby reducing inflammation and the risk of cytokine storms. The study also indicated eganelisib may inhibit the main protease (Mpro) protein of the SARS-CoV-2 virus, a crucial enzyme required for viral replication, potentially offering another therapeutic avenue against COVID-19.[5][6][7]

References

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  1. ^ Evans CA, Liu T, Lescarbeau A, Nair SJ, Grenier L, Pradeilles JA, Glenadel Q, Tibbitts T, Rowley AM, DiNitto JP, Brophy EE, O'Hearn EL, Ali JA, Winkler DG, Goldstein SI, O'Hearn P, Martin CM, Hoyt JG, Soglia JR, Cheung C, Pink MM, Proctor JL, Palombella VJ, Tremblay MR, Castro AC (September 2016). "Discovery of a Selective Phosphoinositide-3-Kinase (PI3K)-γ Inhibitor (IPI-549) as an Immuno-Oncology Clinical Candidate". ACS Med Chem Lett. 7 (9): 862–7. doi:10.1021/acsmedchemlett.6b00238. PMC 5018865. PMID 27660692.
  2. ^ Corey Williams (2016-09-27). "Infinity Pharmaceuticals Inc. Presents Initial Clinical And New Preclinical Data On IPI-549 At Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference". The Smarter Analyst. Archived from the original on 2020-09-22. Retrieved 2020-10-30.
  3. ^ "Infinity Receives Fast Track Designation for Eganelisib in Combination with a Checkpoint Inhibitor and Chemotherapy for First". Bloomberg (Press release). 2020-09-29. Archived from the original on 2020-11-02. Retrieved 2020-10-30.
  4. ^ "CID 91933883 | C30H24N8O2 - PubChem: ClinicalTrials.gov". PubChem. Archived from the original on 2020-11-01. Retrieved 2020-10-30.
  5. ^ Panda SK, Karmakar S, Sen Gupta PS, Rana MK (April 2024). "Can Duvelisib and Eganelisib work for both cancer and COVID-19? Molecular-level insights from MD simulations and enhanced samplings". Physical Chemistry Chemical Physics. 26 (14): 10961–10973. Bibcode:2024PCCP...2610961P. doi:10.1039/d3cp05934k. PMID 38526354.
  6. ^ Shepard RM, Ghebremedhin A, Pratumchai I, Robinson SR, Betts C, Hu J, Sasik R, Fisch KM, Zak J, Chen H, Paradise M, Rivera J, Amjad M, Uchiyama S, Seo H, Campos AD, Dayao DA, Tzipori S, Piedra-Mora C, Das S, Hasteh F, Russo H, Sun X, Xu L, E Alexander LC, Duran JM, Odish M, Pretorius V, Kirchberger NC, Chin SM, Von Schalscha T, Cheresh D, Morrey JD, Alargova R, O'Connell B, Martinot TA, Patel SP, Nizet V, Martinot AJ, Coussens LM, Teijaro JR, Varner JA (July 2024). "PI3Kγ inhibition circumvents inflammation and vascular leak in SARS-CoV-2 and other infections". Science Translational Medicine. 16 (754): eadi6887. doi:10.1126/scitranslmed.adi6887. PMC 11272418. PMID 38959328.
  7. ^ Myers, Judith (3 July 2024). "Fighting COVID-19 With a Cancer Drug". UC San Diego Today. Retrieved 8 July 2024.

Further reading

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  • Drew SL, Thomas-Tran R, Beatty JW, Fournier J, Lawson KV, Miles DH, Mata G, Sharif EU, Yan X, Mailyan AK, Ginn E, Chen J, Wong K, Soni D, Dhanota P, Chen PY, Shaqfeh SG, Meleza C, Pham AT, Chen A, Zhao X, Banuelos J, Jin L, Schindler U, Walters MJ, Young SW, Walker NP, Leleti MR, Powers JP, Jeffrey JL (October 2020). "Discovery of Potent and Selective PI3Kγ Inhibitors". J Med Chem. 63 (19): 11235–11257. doi:10.1021/acs.jmedchem.0c01203. PMID 32865410.
  • Catherine A. Evans*, Tao Liu, André Lescarbeau, Somarajan J. Nair, Louis Grenier, Johan A. Pradeilles, Quentin Glenadel, Thomas Tibbitts, Ann M. Rowley, Jonathan P. DiNitto, Erin E. Brophy, Erin L. O'Hearn, Janid A. Ali, David G. Winkler, Stanley I. Goldstein, Patrick O'Hearn, Christian M. Martin, Jennifer G. Hoyt, John R. Soglia, Culver Cheung, Melissa M. Pink, Jennifer L. Proctor, Vito J. Palombella, Martin R. Tremblay, and Alfredo C. Castro*. Discovery of a Selective Phosphoinositide-3-Kinase (PI3K)-γ Inhibitor (IPI-549) as an Immuno-Oncology Clinical Candidate ACS Med. Chem. Lett. 2016, 7, 9, 862–867; https://doi.org/10.1021/acsmedchemlett.6b00238


 

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