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Activity of the hypoxia-activated prodrug, TH-302, in preclinical human acute myeloid leukemia models.

Portwood S, Lal D, Hsu YC, Vargas R, Johnson MK, Wetzler M, Hart CP, Wang ES.

Clin Cancer Res. 2013 Dec 1;19(23):6506-19. doi: 10.1158/1078-0432.CCR-13-0674. Epub 2013 Oct 2.


Selective tumor hypoxia targeting by hypoxia-activated prodrug TH-302 inhibits tumor growth in preclinical models of cancer.

Sun JD, Liu Q, Wang J, Ahluwalia D, Ferraro D, Wang Y, Duan JX, Ammons WS, Curd JG, Matteucci MD, Hart CP.

Clin Cancer Res. 2012 Feb 1;18(3):758-70. doi: 10.1158/1078-0432.CCR-11-1980. Epub 2011 Dec 19.


Pyruvate induces transient tumor hypoxia by enhancing mitochondrial oxygen consumption and potentiates the anti-tumor effect of a hypoxia-activated prodrug TH-302.

Takakusagi Y, Matsumoto S, Saito K, Matsuo M, Kishimoto S, Wojtkowiak JW, DeGraff W, Kesarwala AH, Choudhuri R, Devasahayam N, Subramanian S, Munasinghe JP, Gillies RJ, Mitchell JB, Hart CP, Krishna MC.

PLoS One. 2014 Sep 25;9(9):e107995. doi: 10.1371/journal.pone.0107995. eCollection 2014.


OSU-A9, an indole-3-carbinol derivative, induces cytotoxicity in acute myeloid leukemia through reactive oxygen species-mediated apoptosis.

Bai LY, Weng JR, Chiu CF, Wu CY, Yeh SP, Sargeant AM, Lin PH, Liao YM.

Biochem Pharmacol. 2013 Nov 15;86(10):1430-40. doi: 10.1016/j.bcp.2013.09.002. Epub 2013 Sep 13.


Molecular and cellular pharmacology of the hypoxia-activated prodrug TH-302.

Meng F, Evans JW, Bhupathi D, Banica M, Lan L, Lorente G, Duan JX, Cai X, Mowday AM, Guise CP, Maroz A, Anderson RF, Patterson AV, Stachelek GC, Glazer PM, Matteucci MD, Hart CP.

Mol Cancer Ther. 2012 Mar;11(3):740-51. doi: 10.1158/1535-7163.MCT-11-0634. Epub 2011 Dec 6.


Targeting the multiple myeloma hypoxic niche with TH-302, a hypoxia-activated prodrug.

Hu J, Handisides DR, Van Valckenborgh E, De Raeve H, Menu E, Vande Broek I, Liu Q, Sun JD, Van Camp B, Hart CP, Vanderkerken K.

Blood. 2010 Sep 2;116(9):1524-7. doi: 10.1182/blood-2010-02-269126. Epub 2010 Jun 7.


Pronounced hypoxia in models of murine and human leukemia: high efficacy of hypoxia-activated prodrug PR-104.

Benito J, Shi Y, Szymanska B, Carol H, Boehm I, Lu H, Konoplev S, Fang W, Zweidler-McKay PA, Campana D, Borthakur G, Bueso-Ramos C, Shpall E, Thomas DA, Jordan CT, Kantarjian H, Wilson WR, Lock R, Andreeff M, Konopleva M.

PLoS One. 2011;6(8):e23108. doi: 10.1371/journal.pone.0023108. Epub 2011 Aug 11.


Regulation of HIF-1α signaling and chemoresistance in acute lymphocytic leukemia under hypoxic conditions of the bone marrow microenvironment.

Frolova O, Samudio I, Benito JM, Jacamo R, Kornblau SM, Markovic A, Schober W, Lu H, Qiu YH, Buglio D, McQueen T, Pierce S, Shpall E, Konoplev S, Thomas D, Kantarjian H, Lock R, Andreeff M, Konopleva M.

Cancer Biol Ther. 2012 Aug;13(10):858-70. doi: 10.4161/cbt.20838. Epub 2012 Aug 1.


Activity of the multikinase inhibitor sorafenib in combination with cytarabine in acute myeloid leukemia.

Hu S, Niu H, Inaba H, Orwick S, Rose C, Panetta JC, Yang S, Pounds S, Fan Y, Calabrese C, Rehg JE, Campana D, Rubnitz JE, Baker SD.

J Natl Cancer Inst. 2011 Jun 8;103(11):893-905. doi: 10.1093/jnci/djr107. Epub 2011 Apr 12.


Elevated HIF-1α expression of acute myelogenous leukemia stem cells in the endosteal hypoxic zone may be a cause of minimal residual disease in bone marrow after chemotherapy.

Matsunaga T, Imataki O, Torii E, Kameda T, Shide K, Shimoda H, Kamiunten A, Sekine M, Taniguchi Y, Yamamoto S, Hidaka T, Katayose K, Kubuki Y, Dobashi H, Bandoh S, Ohnishi H, Fukai F, Shimoda K.

Leuk Res. 2012 Jun;36(6):e122-4. doi: 10.1016/j.leukres.2012.02.028. Epub 2012 Mar 22. No abstract available.


Hypoxia regulates proliferation of acute myeloid leukemia and sensitivity against chemotherapy.

Drolle H, Wagner M, Vasold J, Kütt A, Deniffel C, Sotlar K, Sironi S, Herold T, Rieger C, Fiegl M.

Leuk Res. 2015 Jul;39(7):779-85. doi: 10.1016/j.leukres.2015.04.019. Epub 2015 May 7.


Synergistic induction of apoptosis in multiple myeloma cells by bortezomib and hypoxia-activated prodrug TH-302, in vivo and in vitro.

Hu J, Van Valckenborgh E, Xu D, Menu E, De Raeve H, De Bryune E, Xu S, Van Camp B, Handisides D, Hart CP, Vanderkerken K.

Mol Cancer Ther. 2013 Sep;12(9):1763-73. doi: 10.1158/1535-7163.MCT-13-0123. Epub 2013 Jul 5.


Anti-leukemic activity of lintuzumab (SGN-33) in preclinical models of acute myeloid leukemia.

Sutherland MK, Yu C, Lewis TS, Miyamoto JB, Morris-Tilden CA, Jonas M, Sutherland J, Nesterova A, Gerber HP, Sievers EL, Grewal IS, Law CL.

MAbs. 2009 Sep-Oct;1(5):481-90. Epub 2009 Sep 15.


Induction of tumor arrest and differentiation with prolonged survival by intermittent hypoxia in a mouse model of acute myeloid leukemia.

Liu W, Guo M, Xu YB, Li D, Zhou ZN, Wu YL, Chen Z, Kogan SC, Chen GQ.

Blood. 2006 Jan 15;107(2):698-707. Epub 2005 Sep 15.


Matrine induces apoptosis in human acute myeloid leukemia cells via the mitochondrial pathway and Akt inactivation.

Zhang S, Zhang Y, Zhuang Y, Wang J, Ye J, Zhang S, Wu J, Yu K, Han Y.

PLoS One. 2012;7(10):e46853. doi: 10.1371/journal.pone.0046853. Epub 2012 Oct 8.


Hypoxia-simulating agents and selective stimulation of arsenic trioxide-induced growth arrest and cell differentiation in acute promyelocytic leukemic cells.

Yan H, Peng ZG, Wu YL, Jiang Y, Yu Y, Huang Y, Zhu YS, Zhao Q, Chen GQ.

Haematologica. 2005 Dec;90(12):1607-16.


Imaging biomarkers to monitor response to the hypoxia-activated prodrug TH-302 in the MiaPaCa2 flank xenograft model.

Cárdenas-Rodríguez J, Li Y, Galons JP, Cornnell H, Gillies RJ, Pagel MD, Baker AF.

Magn Reson Imaging. 2012 Sep;30(7):1002-9. doi: 10.1016/j.mri.2012.02.015. Epub 2012 May 1.


Aflibercept exerts antivascular effects and enhances levels of anthracycline chemotherapy in vivo in human acute myeloid leukemia models.

Lal D, Park JA, Demock K, Marinaro J, Perez AM, Lin MH, Tian L, Mashtare TJ, Murphy M, Prey J, Wetzler M, Fetterly GJ, Wang ES.

Mol Cancer Ther. 2010 Oct;9(10):2737-51. doi: 10.1158/1535-7163.MCT-10-0334. Epub 2010 Oct 5.


Inhibition of both thioredoxin reductase and glutathione reductase may contribute to the anticancer mechanism of TH-302.

Li S, Zhang J, Li J, Chen D, Matteucci M, Curd J, Duan JX.

Biol Trace Elem Res. 2010 Sep;136(3):294-301. doi: 10.1007/s12011-009-8544-1. Epub 2009 Oct 17.


TH-302, a hypoxia-activated prodrug with broad in vivo preclinical combination therapy efficacy: optimization of dosing regimens and schedules.

Liu Q, Sun JD, Wang J, Ahluwalia D, Baker AF, Cranmer LD, Ferraro D, Wang Y, Duan JX, Ammons WS, Curd JG, Matteucci MD, Hart CP.

Cancer Chemother Pharmacol. 2012 Jun;69(6):1487-98. doi: 10.1007/s00280-012-1852-8. Epub 2012 Mar 2.

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