Berubicin (RTA 744) hydrochloride is a Doxorubicin analog that can cross the blood-brain barrier. Berubicin hydrochloride inhibits P-gp and MRP1-mediated efflux and suppresses glioblastoma multiforme (GBM). Berubicin hydrochloride exerts toxic effects on leukemia cells by activating nuclear factor κB ( NF-κB ) and induces apoptosis in neuroblastoma cells. Berubicin hydrochloride can be used in the study of tumors related to the nervous system [1] [2] [3] [4] [5].
In Vivo, Berubicin hydrochloride prolongs the survival time of intracranial orthotopic glioma models in mice compared to Temozolomide [5].
In Vitro, Berubicin (0.1-10 μM, 0-5 d) hydrochloride is more effective than Doxorubicin (Dox) in inhibiting SH-SY5Y cell growth[2]. Berubicin (0-10 μM, 0-48 h) hydrochloride induces apoptosis at the lower drug concentrations through caspase-9 and -3-dependent pathways and activating NF-κB, while other mechanisms of cell death may predominate at higher concentrations in SH-SY5Y cells[2]. Berubicin (0-100 μM, 24 h) hydrochloride inhibits three AML cell lines K562, KBM-3, OCIM2 and KBM-5 cells with IC50s of 0.18, < 0.05, < 0.05 μg/mL and 0.5 μM, and induces cell apoptosis in cultured human acute lymphoblastic leukemia (ALL) CEM cells at 0.05 μM[3][4]. Berubicin (0-10 μM, 0-8 h) hydrochloride is more active than Dox in inhibiting DNA synthesis (IC50 = 0.2 μM), activating NF-κB and degradation of IkBα of KBM-5 cells[4].
References:
[1]. Faderl S, et al. WP744, a novel anthracycline with enhanced proapoptotic and antileukemic activity. Anticancer Res. 2001 Nov-Dec;21(6A):3777-84.
[2]. Wu J, Harris NL, Inge TH. Nuclear factor-kappa B and apoptosis inducing factor activation by doxorubicin analog WP744 in SH-SY5Y neuroblastoma cells. J Surg Res. 2004 Dec;122(2):231-9.
[3]. Faderl S, Estrov Z, Kantarjian HM, Harris D, Van Q, Fokt I, Przewloka T, Godlewski C, Woynarowski JM, Priebe W. WP744, a novel anthracycline with enhanced proapoptotic and antileukemic activity. Anticancer Res. 2001 Nov-Dec;21(6A):3777-84. PMID: 11911247.
[4]. Ashikawa K, et al. Evidence that activation of nuclear factor-kappaB is essential for the cytotoxic effects of doxorubicin and its analogues. Biochem Pharmacol. 2004 Jan 15;67(2):353-64.
[5]. Silberman S, et al. RTID-03. DESIGN AND INITIATION OF PIVOTAL STUDIES FOR BERUBICIN, A NOVEL, POTENT TOPOISOMERASE II POISON FOR THE TREATMENT OF RECURRENT GLIOBLASTOMA MULTIFORME (GBM). Neuro Oncol. 2021 Nov 12;23(Suppl 6):vi193.
In Vivo, Berubicin hydrochloride prolongs the survival time of intracranial orthotopic glioma models in mice compared to Temozolomide [5].
In Vitro, Berubicin (0.1-10 μM, 0-5 d) hydrochloride is more effective than Doxorubicin (Dox) in inhibiting SH-SY5Y cell growth[2]. Berubicin (0-10 μM, 0-48 h) hydrochloride induces apoptosis at the lower drug concentrations through caspase-9 and -3-dependent pathways and activating NF-κB, while other mechanisms of cell death may predominate at higher concentrations in SH-SY5Y cells[2]. Berubicin (0-100 μM, 24 h) hydrochloride inhibits three AML cell lines K562, KBM-3, OCIM2 and KBM-5 cells with IC50s of 0.18, < 0.05, < 0.05 μg/mL and 0.5 μM, and induces cell apoptosis in cultured human acute lymphoblastic leukemia (ALL) CEM cells at 0.05 μM[3][4]. Berubicin (0-10 μM, 0-8 h) hydrochloride is more active than Dox in inhibiting DNA synthesis (IC50 = 0.2 μM), activating NF-κB and degradation of IkBα of KBM-5 cells[4].
References:
[1]. Faderl S, et al. WP744, a novel anthracycline with enhanced proapoptotic and antileukemic activity. Anticancer Res. 2001 Nov-Dec;21(6A):3777-84.
[2]. Wu J, Harris NL, Inge TH. Nuclear factor-kappa B and apoptosis inducing factor activation by doxorubicin analog WP744 in SH-SY5Y neuroblastoma cells. J Surg Res. 2004 Dec;122(2):231-9.
[3]. Faderl S, Estrov Z, Kantarjian HM, Harris D, Van Q, Fokt I, Przewloka T, Godlewski C, Woynarowski JM, Priebe W. WP744, a novel anthracycline with enhanced proapoptotic and antileukemic activity. Anticancer Res. 2001 Nov-Dec;21(6A):3777-84. PMID: 11911247.
[4]. Ashikawa K, et al. Evidence that activation of nuclear factor-kappaB is essential for the cytotoxic effects of doxorubicin and its analogues. Biochem Pharmacol. 2004 Jan 15;67(2):353-64.
[5]. Silberman S, et al. RTID-03. DESIGN AND INITIATION OF PIVOTAL STUDIES FOR BERUBICIN, A NOVEL, POTENT TOPOISOMERASE II POISON FOR THE TREATMENT OF RECURRENT GLIOBLASTOMA MULTIFORME (GBM). Neuro Oncol. 2021 Nov 12;23(Suppl 6):vi193.