{{cs1 config|name-list-style=vanc|display-authors=6}} {{Infobox drug | drug_name = | image = Rezatapopt_structure.png | image_class = skin-invert-image | width = 200px | caption =
<!-- Clinical data --> | pronounce = | tradename = | Drugs.com = | MedlinePlus = | licence_CA = | licence_EU = | DailyMedID = | licence_US = | pregnancy_AU = | pregnancy_category = | dependency_liability = | addiction_liability = | routes_of_administration = | class = | ATC_prefix = | ATC_suffix =
<!-- Legal status --> | legal_status =
<!-- Pharmacokinetic data --> | bioavailability = | protein_bound = | metabolism = | metabolites = | onset = | elimination_half-life = | duration_of_action = | excretion =
<!-- Identifiers --> | CAS_number = 2636846-41-6 | PubChem = 156195543 | IUPHAR_ligand = | DrugBank = | ChemSpiderID = | UNII = | KEGG = | ChEBI = | ChEMBL = | NIAID_ChemDB = | PDB_ligand = | synonyms =
<!-- Chemical data --> | IUPAC_name = <nowiki>4-[3-[4-[[(3S,4R)-3-fluoro-1-methylpiperidin-4-yl]amino]-1-(2,2,2-trifluoroethyl)indol-2-yl]prop-2-ynylamino]-3-methoxy-N-methylbenzamide</nowiki> | C=28 | H=31 | F=4 | N=5 | O=2 | SMILES = CNC(=O)C1=CC(=C(C=C1)NCC#CC2=CC3=C(C=CC=C3N2CC(F)(F)F)N[C@@H]4CCN(C[C@@H]4F)C)OC | StdInChI = 1S/C28H31F4N5O2/c1-33-27(38)18-9-10-24(26(14-18)39-3)34-12-5-6-19-15-20-22(35-23-11-13-36(2)16-21(23)29)7-4-8-25(20)37(19)17-28(30,31)32/h4,7-10,14-15,21,23,34-35H,11-13,16-17H2,1-3H3,(H,33,38)/t21-,23+/m0/s1 | StdInChIKey = NKRKBSQLUPEVCZ-JTHBVZDNSA-N }}
'''Rezatapopt''' ('''PC14586''') is a drug which acts as a p53 reactivator and has potential applications in cancer treatment. The p53 family of proteins are regulatory molecules which usually have an important role in preventing tissues from becoming cancerous. Mutations in p53 are one of the most common steps involved in the progression of tissues toward a cancerous state, and around 50% of human tumours show mutations in p53 which reduce or abolish its activity. One of the more common mutations is Y220C, which leads to an inactive form of p53. Rezatapopt binds to the Y220C mutant form of p53 and causes a conformational change which restores its anti-cancer activity, even though the protein is still mutated. It also shows some restoration of activity of other p53 mutants such as Y220N and Y220S. Rezatapopt has shown promising results in Phase I/II human clinical trials, but with some indications that reactivation of p53 can stimulate further mutation into forms which are no longer activated by rezatapopt. This means that if rezatapopt or drugs like it end up being approved for medical use, it will most likely be as part of a cocktail approach alongside other anti-cancer drugs, rather than as a single agent.<ref>{{cite journal | vauthors = Vu BT, Dominique R, Fahr BJ, Li HH, Fry DC, Xu L, Yang H, Puzio-Kuter A, Good A, Liu B, Huang KS, Tanaka N, Davis TW, Dumble ML | title = Discovery of Rezatapopt (PC14586), a First-in-Class, Small-Molecule Reactivator of p53 Y220C Mutant in Development | journal = ACS Medicinal Chemistry Letters | volume = 16 | issue = 1 | pages = 34–39 | date = January 2025 | pmid = 39811143 | doi = 10.1021/acsmedchemlett.4c00379 | pmc = 11726359 }}</ref><ref>{{cite journal | vauthors = Puzio-Kuter AM, Xu L, McBrayer MK, Dominique R, Li HH, Fahr BJ, Brown AM, Wiebesiek AE, Russo BM, Mulligan CL, Yang H, Battaglia J, Robell KA, Thomas DH, Huang KS, Solovyov A, Greenbaum BD, Oliner JD, Davis TW, Dumble ML, Johnson ML, Xiong S, Yang P, Lozano G, Fellous MM, Vu BT, Schram AM, Levine AJ, Poyurovsky MV | title = Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator | journal = Cancer Discovery | volume = 15 | issue = 6 | pages = 1159–1179 | date = June 2025 | pmid = 39945593 | doi = 10.1158/2159-8290.CD-24-1421 | pmc = 12130801 }}</ref><ref>{{cite journal | vauthors = Ma Z, Shen Q, Zhou J | title = Rezatapopt (PC14586): A First-in-Class Small Molecule p53 Y220C Mutant Protein Stabilizer in Clinical Trials | journal = Journal of Medicinal Chemistry | volume = 68 | issue = 7 | pages = 6847–6849 | date = April 2025 | pmid = 40110876 | doi = 10.1021/acs.jmedchem.5c00670 | pmc = 12507176 }}</ref><ref>{{cite journal | vauthors = Papavassiliou KA, Vassiliou AG, Papavassiliou AG | date = September 2025 | title = Rezatapopt: A promising small-molecule "refolder" specific for TP53<sup>Y220C</sup> mutant tumors | journal = Neoplasia | volume = 67 | article-number = 101201 | doi = 10.1016/j.neo.2025.101201 | pmc = 12221603 | pmid = 40543428 }}</ref><ref>{{cite journal | vauthors = Carter BZ, Mak PY, Ayoub E, Wu X, Ke B, Nishida Y, Futreal A, Ostermann LB, Bedoy AD, Boettcher S, DiNardo CD, Puzio-Kuter A, Poyurovsky MV, Levine A, Andreeff M | title = Restoring p53 wild-type conformation in TP53-Y220C-mutant acute myeloid leukemia | journal = Blood | volume = 146 | issue = 21 | pages = 2574–2588 | date = November 2025 | pmid = 40608889 | doi = 10.1182/blood.2025028935 | pmc = 12320512 }}</ref><ref>{{cite journal | vauthors = Dumbrava EE, Shapiro GI, Parikh AR, Johnson ML, Tolcher AW, Thompson JA, El-Khoueiry AB, Vandross AL, Kummar S, Shepard DR, LeDuke K, Sheehan L, Alland L, Haque A, Jalota D, Fellous M, Schram AM | title = Phase 1 Study of Rezatapopt, a p53 Reactivator, in <i>TP53</i> Y220C-Mutated Tumors | journal = The New England Journal of Medicine | volume = 394 | issue = 9 | pages = 872–883 | date = February 2026 | pmid = 41740031 | doi = 10.1056/NEJMoa2508820 }}</ref><ref>{{cite journal | vauthors = Mavridi D, Funk JS, Balourdas DI, Krämer A, Khan Tareque R, Timofeev O, Spencer J, Stiewe T, Joerger AC | date = February 2026 | title = Targeting the p53 cancer mutants Y220C, Y220N, and Y220S with the small-molecule stabilizer rezatapopt | journal = Cell Death & Disease | volume = 17 | issue = 1 | article-number = 268 | doi = 10.1038/s41419-026-08492-9 | pmc = 13004867 | pmid = 41748563 }}</ref><ref>{{cite journal | vauthors = Fece de la Cruz F, Varkaris A, Patel PS, Kushner EW, Morales-Giron AA, Lee SS, Singh A, Kim CT, Norden BL, Ehnstrom S, Riedl JM, Curtis JM, Barnes H, Kehlmann AM, Chevalier NJ, Okuma HS, Patel M, Wirth LJ, Connell B, Nugent F, Pappas L, Lau K, Juric D, Hopkins JL, Guiley KZ, Shokat KM, Gulhan DC, Parikh AR, Corcoran RB | title = Acquired On-Target Alterations Drive Clinical Resistance to p53-Y220C Reactivators | journal = Cancer Discovery | volume = 16 | issue = 4 | pages = 677–685 | date = April 2026 | pmid = 41504628 | doi = 10.1158/2159-8290.CD-25-1761 | pmc = 13040207 }}</ref><ref>{{cite journal | vauthors = Chen S, Shepard HM, Lu M | title = Reactivating p53 mutants selectively in patients | journal = Cancer Cell | volume = 44 | issue = 4 | pages = 715–717 | date = April 2026 | pmid = 41932331 | doi = 10.1016/j.ccell.2026.03.009 }}</ref>
== References == {{reflist}}
{{pharm-stub}}
Category:Indoles