Granted Patent
B2
US 12,679,855 · App. 17/425,472 · Granted Jul 14, 2026
Inhibitors of the enzyme enolase for precision oncology
Inventors:
Florian Muller (Houston, TX); Victoria Yan (Houston, TX); Kristine Yang (Houston, TX); Elliot Ballato (Houston, TX); Cong-dat Pham (Houston, TX)
View Patent ↗
Loading inventors, assignments & file history…
Abstract
Provided herein are compounds of the formula: wherein the variables are defined herein. The present disclosure also provides pharmaceutical compositions comprising the compounds disclosed herein as well as methods of treatment using the compounds and/or compositions disclosed herein. Such compounds and compositions may be used, for example, for the inhibition of enolase enzymes.
Claims (6)
1 . A compound of the formula:
or a pharmaceutically acceptable salt thereof.
2 . A pharmaceutical composition comprising:
(a) a compound of claim 1 ; and
(b) an excipient.
3 . A method of treating cancer in a patient in need thereof comprising administering to the patient a therapeutically effective amount of a compound or composition of claim 1 .
Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Oct 22, 2021
From: MULLER, FLORIAN; YAN, VICTORIA; YANG, KRISTINE; BALLATO, ELLIOT; PHAM, CONG-DAT
To: BOARD OF REGENTS, THE UNIVERSITY OF TEXAS SYSTEM
Reel/Frame 057876/0667 →
Continuity (2)
Provisional Application
62797315
· Jan 27, 2019
References Cited (27)
US 20090203697A1
· Kimura et al.
· 2009
[cited by applicant]
US 20090270623A1
· Shimomura et al.
· 2009
[cited by applicant]
WO WO2016145113
· 2016
[cited by applicant]
Peng “Discovery of an Orally Active and Liver-Targeted Prodrug of 5-Fluoro-2′-Deoxyuridine for the Treatment of Hepatocellular Carcinoma.” Journal of Medicinal Chemistry, 59(8), 3661-3670, 2016.
[cited by examiner]
Meier, “cyclo-Sal-2′,3′-dideoxy-2′,3′-didehydrothymidine Monophosphate (cyclo-Sal-d4TMP): Synthesis and Antiviral Evaluation of a New d4TMP Delivery System.” Journal of Medicinal Chemistry, 1998, 41(9), 1417-1427.
[cited by examiner]
Hecker “Prodrugs of Phosphates and Phosphonates” J. Med. Chem. 2008, 51, 2328-2345.
[cited by examiner]
Youcef Mehellou “The ProTide Prodrug Technology: From the Concept to the Clinic” J. Med. Chem. 2018, 61, 2211-2226.
[cited by examiner]
Smith “Relevance of Half-Life in Drug Design Miniperspective” J. Med. Chem. 2018, 61, 4273-4282.
[cited by examiner]
Borch et al., “Synthesis and evaluation of nitroheterocyclic phosphoramidates as hypoxia-selective alkylating agents,”
[cited by applicant]
Jung et al., “A unique small molecule inhibitor of enolase clarifies its role in fundamental biological processes,”
[cited by applicant]
Leonard et al., “SF2312 is a natural phosphonate inhibitor of enolase,”
[cited by applicant]
Lin et al., “Eradication of ENO1-deleted glioblastoma through collateral lethality,”
[cited by applicant]
Muller et al., “In vitro enzymatic activity assay for ENOLASE in mammalian cells in culture,”
[cited by applicant]
Muller et al., “Passenger deletions generate therapeutic vulnerabilities in cancer,”
[cited by applicant]
Muller et al., “Synthesis of mixed, hypoxia-activated phosphoramidate esters for the inhibition of Enolase in ENO1-deleted glioblastoma,” In: Proceedings of the American Association for Cancer Research Annual Meeting 20…
[cited by applicant]
O'Connor et al., “Design synthesis and evaluation of molecularly targeted hypoxia-activated prodrugs,”
[cited by applicant]
Olbryt et al., “Global gene expression profiling in three tumor cell lines subjected to experimental cycling and chronic hypoxia,”
[cited by applicant]
PCT International Preliminary Report on Patentability issued in International Application No. PCT/US2020/015253, mailed Aug. 5, 2021.
[cited by applicant]
PCT International Search Report and Written Opinion issued in International Application No. PCT/US2020/015253, mailed May 21, 2020.
[cited by applicant]
Satani et al., “ENOblock does not inhibit the activity of the glycolytic enzyme enolase,”
[cited by applicant]
Wiemer et al., “Prodrugs of phosphonates and phosphates: crossing the membrane barrier,”
[cited by applicant]
Yan et al., “Potent, non-carboxylesterase-labile pro-drugs of the Enolase inhibitor HEX for the treatment of ENO1-deleted glioblastoma,” Abstract, MEDI 159, Division of Medicinal Chemistry Scientific Abstracts, 257
[cited by applicant]
Zhou et al., “Safety and pharmacokinetics of IDX184, a liver-targeted nucleotide polymerase inhibitor of hepatitis C virus, in healthy subjects,”
[cited by applicant]
Lin, Y-H. et al., “An enolase inhibitor for the targeted treatment of ENO1-deleted cancers,”
[cited by applicant]
Yan, C. C et al., “Prodrugs of a 1-Hydroxy-2-oxopiperidin-3-yl Phosphonate Enolase Inhibitor for the Treatment of ENO1-Deleted Cancers,”
[cited by applicant]