Berubicin hydrochloride  (Synonyms: RTA 744; WP 744; WP 769 hydrochloride)

Berubicin (RTA 744) hydrochloride is a Doxorubicin (HY-15142A) 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]}.

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].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Berubicin hydrochloride prolongs the survival time of intracranial orthotopic glioma models in mice compared to Temozolomide (HY-17364)^[5].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

670.10

C₃₄H₃₆ClNO₁₁

293736-67-1

Solid

Brown to red

OC1=C2C([C@@]([H])(O[C@H]3C[C@H](N)[C@H](OCC4=CC=CC=C4)[C@H](C)O3)C[C@@](C(CO)=O)(O)C2)=C(O)C5=C1C(C6=CC=CC(OC)=C6C5=O)=O.Cl

Room temperature in continental US; may vary elsewhere.

4°C, sealed storage, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

• [1]. Faderl S, et al. WP744, a novel anthracycline with enhanced proapoptotic and antileukemic activity. Anticancer Res. 2001 Nov-Dec;21(6A):3777-84.  [Content Brief]

  [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.  [Content Brief]

  [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.  [Content Brief]

  [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.  [Content Brief]

  [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.