PU-H71

• CAT Number: R039746
• CAS Number: 873436-91-0
• Molecular Formula: C₁₈H₂₁IN₆O₂S
• Molecular Weight: 512.37
• Purity: ≥95%
• Target: HSP
• Solubility: Soluble in DMSO > 10 mM
• Storage: Store at -20°C
• InChI: InChI=1S/C18H21IN6O2S/c1-10(2)21-4-3-5-25-17-15(16(20)22-8-23-17)24-18(25)28-14-7-13-12(6-11(14)19)26-9-27-13/h6-8,10,21H,3-5,9H2,1-2H3,(H2,20,22,23)
• InChIKey: SUPVGFZUWFMATN-UHFFFAOYSA-N
• SMILES: CC(C)NCCCN1C2=C(C(=NC=N2)N)N=C1SC3=C(C=C4C(=C3)OCO4)I

PU-H71 (CAT: R039746) is a potent anticancer agent known for its mode of action as a heat shock protein 90 (Hsp90) inhibitor. Pharmacologically, it functions by disrupting the chaperone role of Hsp90, leading to the degradation of client proteins critical for cancer cell growth and survival. While not approved for clinical use, PU-H71 plays a pivotal role in cancer research, particularly in preclinical studies.

Reference

1: Taldone T, Zatorska D, Ochiana SO, Smith-Jones P, Koziorowski J, Dunphy MP, Zanzonico P, Bolaender A, Lewis JS, Larson SM, Chiosis G, Pillarsetty NV. Radiosynthesis of the iodine-124 labeled Hsp90 inhibitor PU-H71. J Labelled Comp Radiopharm. 2016 Mar;59(3):129-32. doi: 10.1002/jlcr.3369. PubMed PMID: 26806023; PubMed Central PMCID: PMC4779400.2: Trendowski M. PU-H71: An improvement on nature/’s solutions to oncogenic Hsp90 addiction. Pharmacol Res. 2015 Sep;99:202-16. doi: 10.1016/j.phrs.2015.06.007. Review. PubMed PMID: 26117427.3: Lee Y, Li HK, Masaoka A, Sunada S, Hirakawa H, Fujimori A, Nickoloff JA, Okayasu R. The purine scaffold Hsp90 inhibitor PU-H71 sensitizes cancer cells to heavy ion radiation by inhibiting DNA repair by homologous recombination and non-homologous end joining. Radiother Oncol. 2016 Oct;121(1):162-168. doi: 10.1016/j.radonc.2016.08.029. PubMed PMID: 27666928; PubMed Central PMCID: PMC5110220.4: Li HK, Matsumoto Y, Furusawa Y, Kamada T. PU-H71, a novel Hsp90 inhibitor, as a potential cancer-specific sensitizer to carbon-ion beam therapy. J Radiat Res. 2016 Sep;57(5):572-575. PubMed PMID: 27242340; PubMed Central PMCID: PMC5045081.5: Ambati SR, Lopes EC, Kosugi K, Mony U, Zehir A, Shah SK, Taldone T, Moreira AL, Meyers PA, Chiosis G, Moore MA. Pre-clinical efficacy of PU-H71, a novel HSP90 inhibitor, alone and in combination with bortezomib in Ewing sarcoma. Mol Oncol. 2014 Mar;8(2):323-36. doi: 10.1016/j.molonc.2013.12.005. PubMed PMID: 24388362; PubMed Central PMCID: PMC3982393.6: Liu M, Wang J, Wu X, Wang E, Baptista D, Scott B, Liu P. HPLC method development, validation and impurity characterization for an antitumor Hsp90 inhibitor-PU-H71 (NSC 750424). J Pharm Biomed Anal. 2014 Feb;89:34-41. doi: 10.1016/j.jpba.2013.10.021. PubMed PMID: 24252723; PubMed Central PMCID: PMC3954645.7: Guo A, Lu P, Lee J, Zhen C, Chiosis G, Wang YL. HSP90 stabilizes B-cell receptor kinases in a multi-client interactome: PU-H71 induces CLL apoptosis in a cytoprotective microenvironment. Oncogene. 2017 Jan 23. doi: 10.1038/onc.2016.494. [Epub ahead of print] PubMed PMID: 28114285.8: Segawa T, Fujii Y, Tanaka A, Bando S, Okayasu R, Ohnishi K, Kubota N. Radiosensitization of human lung cancer cells by the novel purine-scaffold Hsp90 inhibitor, PU-H71. Int J Mol Med. 2014 Mar;33(3):559-64. doi: 10.3892/ijmm.2013.1594. PubMed PMID: 24366006.9: Qu Z, Wang S, Teng R, Yi X. PU-H71 effectively induces degradation of IκB kinase β in the presence of TNF-α. Mol Cell Biochem. 2014 Jan;386(1-2):135-42. doi: 10.1007/s11010-013-1852-y. PubMed PMID: 24114662.10: Gallerne C, Prola A, Lemaire C. Hsp90 inhibition by PU-H71 induces apoptosis through endoplasmic reticulum stress and mitochondrial pathway in cancer cells and overcomes the resistance conferred by Bcl-2. Biochim Biophys Acta. 2013 Jun;1833(6):1356-66. doi: 10.1016/j.bbamcr.2013.02.014. PubMed PMID: 23485394.11: Lisi L, McGuire S, Sharp A, Chiosis G, Navarra P, Feinstein DL, Dello Russo C. The novel HSP90 inhibitor, PU-H71, suppresses glial cell activation but weakly affects clinical signs of EAE. J Neuroimmunol. 2013 Feb 15;255(1-2):1-7. doi: 10.1016/j.jneuroim.2012.10.008. PubMed PMID: 23123171; PubMed Central PMCID: PMC3710720.12: Taldone T, Rodina A, Dagama Gomes EM, Riolo M, Patel HJ, Alonso-Sabadell R, Zatorska D, Patel MR, Kishinevsky S, Chiosis G. Synthesis and evaluation of cell-permeable biotinylated PU-H71 derivatives as tumor Hsp90 probes. Beilstein J Org Chem. 2013 Mar 15;9:544-56. doi: 10.3762/bjoc.9.60. PubMed PMID: 23616796; PubMed Central PMCID: PMC3628991.13: Usmani SZ, Bona RD, Chiosis G, Li Z. The anti-myeloma activity of a novel purine scaffold HSP90 inhibitor PU-H71 is via inhibition of both HSP90A and HSP90B1. J Hematol Oncol. 2010 Oct 26;3:40. doi: 10.1186/1756-8722-3-40. PubMed PMID: 20977755; PubMed Central PMCID: PMC2974653.14: Caldas-Lopes E, Cerchietti L, Ahn JH, Clement CC, Robles AI, Rodina A, Moulick K, Taldone T, Gozman A, Guo Y, Wu N, de Stanchina E, White J, Gross SS, Ma Y, Varticovski L, Melnick A, Chiosis G. Hsp90 inhibitor PU-H71, a multimodal inhibitor of malignancy, induces complete responses in triple-negative breast cancer models. Proc Natl Acad Sci U S A. 2009 May 19;106(20):8368-73. doi: 10.1073/pnas.0903392106. PubMed PMID: 19416831; PubMed Central PMCID: PMC2688867.15: Goldstein RL, Yang SN, Taldone T, Chang B, Gerecitano J, Elenitoba-Johnson K, Shaknovich R, Tam W, Leonard JP, Chiosis G, Cerchietti L, Melnick A. Pharmacoproteomics identifies combinatorial therapy targets for diffuse large B cell lymphoma. J Clin Invest. 2015 Nov 3;125(12):4559-71. doi: 10.1172/JCI80714. PubMed PMID: 26529251; PubMed Central PMCID: PMC4665772.16: Yuzefovych Y, Blasczyk R, Huyton T. Oncogenic acidic nuclear phosphoproteins ANP32C/D are novel clients of heat shock protein 90. Biochim Biophys Acta. 2015 Oct;1853(10 Pt A):2338-48. doi: 10.1016/j.bbamcr.2015.06.007. PubMed PMID: 26112988.17: Rouhi A, Miller C, Grasedieck S, Reinhart S, Stolze B, Döhner H, Kuchenbauer F, Bullinger L, Fröhling S, Scholl C. Prospective identification of resistance mechanisms to HSP90 inhibition in KRAS mutant cancer cells. Oncotarget. 2016 Dec 9. doi: 10.18632/oncotarget.13841. [Epub ahead of print] PubMed PMID: 28032595.18: Nayar U, Lu P, Goldstein RL, Vider J, Ballon G, Rodina A, Taldone T, Erdjument-Bromage H, Chomet M, Blasberg R, Melnick A, Cerchietti L, Chiosis G, Wang YL, Cesarman E. Targeting the Hsp90-associated viral oncoproteome in gammaherpesvirus-associated malignancies. Blood. 2013 Oct 17;122(16):2837-47. doi: 10.1182/blood-2013-01-479972. PubMed PMID: 23943653; PubMed Central PMCID: PMC3798998.19: Shahinas D, Folefoc A, Taldone T, Chiosis G, Crandall I, Pillai DR. A purine analog synergizes with chloroquine (CQ) by targeting Plasmodium falciparum Hsp90 (PfHsp90). PLoS One. 2013 Sep 30;8(9):e75446. doi: 10.1371/journal.pone.0075446. PubMed PMID: 24098696; PubMed Central PMCID: PMC3787104.20: Jeong H, Kang BH, Lee C. Crystallization and preliminary X-ray diffraction analysis of Trap1 complexed with Hsp90 inhibitors. Acta Crystallogr F Struct Biol Commun. 2014 Dec 1;70(Pt 12):1683-7. doi: 10.1107/S2053230X14024959. PubMed PMID: 25484226; PubMed Central PMCID: PMC4259240.