PNU-159682

• CAT Number: I002555
• CAS Number: 202350-68-3
• Molecular Formula: C32H35NO13
• Molecular Weight: 641.62
• Purity: ≥95%
• Target: Topoisomerase I inhibitor
• Solubility: 10 mM in DMSO
• Storage: 2–8 °C
• IC50: 0.1-0.5 nM (HT-29; DU145; Jurkat cell lines, etc)
• IUPAC Name: (7S,9S)-6,9,11-trihydroxy-9-(2-hydroxyacetyl)-4-methoxy-7-[[(2S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl-5,8,11-trioxa-1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-8,10-dihydro-7H-tetracene-5,12-dione
• InChI: InChI=1S/C32H35NO13/c1-13-29-16(33-7-8-43-31(42-3)30(33)46-29)9-20(44-13)45-18-11-32(40,19(35)12-34)10-15-22(18)28(39)24-23(26(15)37)25(36)14-5-4-6-17(41-2)21(14)27(24)38/h4-6,13,16,18,20,29-31,34,37,39-40H,7-12H2,1-3H3/t13-,16-,18-,20-,29+,30+,31-,32-/m0/s1
• InChIKey: SLURUCSFDHKXFR-WWMWMSKMSA-N
• SMILES: CC1C2C(CC(O1)OC3CC(CC4=C3C(=C5C(=C4O)C(=O)C6=C(C5=O)C(=CC=C6)OC)O)(C(=O)CO)O)N7CCOC(C7O2)OC

PNU-159682（Cat No.:I002555） is a DNA topoisomerase I (TopoI) inhibitor derived from the anthracycline neomycin metabolite. It exhibits strong cytotoxicity and is particularly effective in inhibiting TopoI. In the synthesis of antibody-drug conjugates (ADCs), PNU-159682 serves as a potent and well-tolerated cytotoxin, surpassing the efficacy of doxorubicin. Moreover, PNU-159682 can be utilized in EDV nano-cell technology to overcome drug resistance, enhancing its therapeutic potential in treating cancer and other diseases.

Reference

1:Virtual Cross-Linking of the Active Nemorubicin Metabolite PNU-159682 to Double-Stranded DNA. Scalabrin M, Quintieri L, Palumbo M, Riccardi Sirtori F, Gatto B.Chem Res Toxicol. 2017 Feb 20;30(2):614-624. doi: 10.1021/acs.chemrestox.6b00362. Epub 2017 Jan 25. PMID: 28068470 2:The interaction of nemorubicin metabolite PNU-159682 with DNA fragments d(CGTACG)(2), d(CGATCG)(2) and d(CGCGCG)(2) shows a strong but reversible binding to G:C base pairs. Mazzini S, Scaglioni L, Mondelli R, Caruso M, Sirtori FR.Bioorg Med Chem. 2012 Dec 15;20(24):6979-88. doi: 10.1016/j.bmc.2012.10.033. Epub 2012 Nov 3. PMID: 23154079 3:In vitro hepatic conversion of the anticancer agent nemorubicin to its active metabolite PNU-159682 in mice, rats and dogs: a comparison with human liver microsomes. Quintieri L, Fantin M, Palatini P, De Martin S, Rosato A, Caruso M, Geroni C, Floreani M.Biochem Pharmacol. 2008 Sep 15;76(6):784-95. doi: 10.1016/j.bcp.2008.07.003. Epub 2008 Jul 11. PMID: 18671948 4:Formation and antitumor activity of PNU-159682, a major metabolite of nemorubicin in human liver microsomes. Quintieri L, Geroni C, Fantin M, Battaglia R, Rosato A, Speed W, Zanovello P, Floreani M.Clin Cancer Res. 2005 Feb 15;11(4):1608-17. PMID: 15746066 Free Article