TH-302

• CAT Number: I005478
• CAS Number: 918633-87-1
• Molecular Formula: C9H16Br2N5O4P
• Molecular Weight: 449.04
• Purity: ≥95%
• Target: Topoisomerase
• Solubility: DMSO 100 mg/ml
• Storage: 3 years -20℃ powder
• IUPAC Name: 2-bromo-N-[(2-bromoethylamino)-[(3-methyl-2-nitroimidazol-4-yl)methoxy]phosphoryl]ethanamine
• InChI: InChI=1S/C9H16Br2N5O4P/c1-15-8(6-12-9(15)16(17)18)7-20-21(19,13-4-2-10)14-5-3-11/h6H,2-5,7H2,1H3,(H2,13,14,19)
• InChIKey: UGJWRPJDTDGERK-UHFFFAOYSA-N
• SMILES: BrCCNP(OCC1=CN=C([N+]([O-])=O)N1C)(NCCBr)=O

TH-302 (Cat.No:I005478) is selective hypoxia-activated prodrug targeting hypoxic regions of solid tumors with IC50 of 19 nM, demonstrates 270-fold enhanced cytotoxicity under hypoxia versus their potency under aerobic conditions, stable to cytochrome P450 metabolism.TH-302 is a newly developed antineoplastic drug which represents a potential new class of tumor selective hypoxia-activated prodrugs (HAPs).

Reference

1:Hypoxia-activated prodrug TH-302 decreased survival rate of canine lymphoma cells under hypoxic condition. Yamazaki H, Lai YC, Tateno M, Setoguchi A, Goto-Koshino Y, Endo Y, Nakaichi M, Tsujimoto H, Miura N.PLoS One. 2017 May 10;12(5):e0177305. doi: 10.1371/journal.pone.0177305. eCollection 2017. PMID: 28489881 Free PMC Article2:Phase I study of pazopanib plus TH-302 in advanced solid tumors. Riedel RF, Meadows KL, Lee PH, Morse MA, Uronis HE, Blobe GC, George DJ, Crawford J, Niedzwiecki D, Rushing CN, Arrowood CC, Hurwitz HI.Cancer Chemother Pharmacol. 2017 Mar;79(3):611-619. doi: 10.1007/s00280-017-3256-2. Epub 2017 Feb 25. PMID: 28238078 3:Hypoxia Imaging With PET Correlates With Antitumor Activity of the Hypoxia-Activated Prodrug Evofosfamide (TH-302) in Rodent Glioma Models. Stokes AM, Hart CP, Quarles CC.Tomography. 2016 Sep;2(3):229-237. PMID: 27752544 4:A phase 1 /’window-of-opportunity/’ trial testing evofosfamide (TH-302), a tumour-selective hypoxia-activated cytotoxic prodrug, with preoperative chemoradiotherapy in oesophageal adenocarcinoma patients. Larue RT, Van De Voorde L, Berbée M, van Elmpt WJ, Dubois LJ, Panth KM, Peeters SG, Claessens A, Schreurs WM, Nap M, Warmerdam FA, Erdkamp FL, Sosef MN, Lambin P.BMC Cancer. 2016 Aug 17;16:644. doi: 10.1186/s12885-016-2709-z. PMID: 27535748 Free PMC Article5:Targeting hypoxic microenvironment of pancreatic xenografts with the hypoxia-activated prodrug TH-302. Lohse I, Rasowski J, Cao P, Pintilie M, Do T, Tsao MS, Hill RP, Hedley DW.Oncotarget. 2016 Jun 7;7(23):33571-80. doi: 10.18632/oncotarget.9654. PMID: 27248663 Free PMC Article6:MR Imaging Biomarkers to Monitor Early Response to Hypoxia-Activated Prodrug TH-302 in Pancreatic Cancer Xenografts. Zhang X, Wojtkowiak JW, Martinez GV, Cornnell HH, Hart CP, Baker AF, Gillies R.PLoS One. 2016 May 26;11(5):e0155289. doi: 10.1371/journal.pone.0155289. eCollection 2016. PMID: 27227903 Free PMC Article7:Comparison of hypoxia-activated prodrug evofosfamide (TH-302) and ifosfamide in preclinical non-small cell lung cancer models. Sun JD, Liu Q, Ahluwalia D, Ferraro DJ, Wang Y, Jung D, Matteucci MD, Hart CP.Cancer Biol Ther. 2016 Apr 2;17(4):371-80. doi: 10.1080/15384047.2016.1139268. Epub 2016 Jan 28. PMID: 26818215 Free PMC Article8:Anticancer efficacy of the hypoxia-activated prodrug evofosfamide (TH-302) in osteolytic breast cancer murine models. Liapis V, Zinonos I, Labrinidis A, Hay S, Ponomarev V, Panagopoulos V, Zysk A, DeNichilo M, Ingman W, Atkins GJ, Findlay DM, Zannettino AC, Evdokiou A.Cancer Med. 2016 Mar;5(3):534-45. doi: 10.1002/cam4.599. Epub 2016 Jan 9. PMID: 26749324 Free PMC Article9:Hypoxia-Activated Prodrug TH-302 Targets Hypoxic Bone Marrow Niches in Preclinical Leukemia Models. Benito J, Ramirez MS, Millward NZ, Velez J, Harutyunyan KG, Lu H, Shi YX, Matre P, Jacamo R, Ma H, Konoplev S, McQueen T, Volgin A, Protopopova M, Mu H, Lee J, Bhattacharya PK, Marszalek JR, Davis RE, Bankson JA, Cortes JE, Hart CP, Andreeff M, Konopleva M.Clin Cancer Res. 2016 Apr 1;22(7):1687-98. doi: 10.1158/1078-0432.CCR-14-3378. Epub 2015 Nov 24. PMID: 26603259 Free PMC Article10:[TH-302: a new hypoxia-activated cytostatic agent in pancreatic cancer treatment]. Schmalz C, Dunst J.Strahlenther Onkol. 2015 Oct;191(10):819-20. doi: 10.1007/s00066-015-0877-4. German. No abstract available. PMID: 26385861