Aldoxorubicin - CAS 151038-96-9
Catalog number: 151038-96-9
Category: Inhibitor
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Antibody-drug Conjugates
Aldoxorubicin, also known as INNO-206,  is the 6-maleimidocaproyl hydrazone derivative prodrug of the anthracycline antibiotic doxorubicin (DOXO-EMCH) with antineoplastic activity. Following intravenous administration, doxorubicin prodrug INNO-206 binds selectively to the cysteine-34 position of albumin via its maleimide moiety. Doxorubicin is released from the albumin carrier after cleavage of the acid-sensitive hydrazone linker within the acidic environment of tumors and, once located intracellularly, intercalates DNA, inhibits DNA synthesis, and induces apoptosis. Albumin tends to accumulate in solid tumors as a result of high metabolic turnover, rapid angiogenesis, hyervasculature, and impaired lymphatic drainage. Because of passive accumulation within tumors, this agent may improve the therapeutic effects of doxorubicin while minimizing systemic toxicity.
Red solid powder
DOXO-EMCH, INNO-206, INNO206; INNO 206; Aldoxorubicin
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Innovive Pharmaceuticals and CytRx Corporation
1.A phase 1B/2 study of aldoxorubicin in patients with soft tissue sarcoma.
Chawla SP1, Chua VS, Hendifar AF, Quon DV, Soman N, Sankhala KK, Wieland DS, Levitt DJ. Cancer. 2015 Feb 15;121(4):570-9. doi: 10.1002/cncr.29081. Epub 2014 Oct 13.
BACKGROUND: Aldoxorubicin, a prodrug of doxorubicin, covalently binds to serum albumin, allowing for the administration of much higher doses of doxorubicin in a previous clinical study. The current phase 1B/2 study evaluated the safety of aldoxorubicin, including preliminary efficacy and safety of its maximum tolerated dose (MTD).
2.Therapeutic efficacy of aldoxorubicin in an intracranial xenograft mouse model of human glioblastoma.
Marrero L1, Wyczechowska D2, Musto AE3, Wilk A2, Vashistha H2, Zapata A2, Walker C2, Velasco-Gonzalez C4, Parsons C2, Wieland S5, Levitt D5, Reiss K2, Prakash O2. Neoplasia. 2014 Oct 23;16(10):874-82. doi: 10.1016/j.neo.2014.08.015. eCollection 2014.
Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor with a median survival of 12 to 15 months after diagnosis. Acquired chemoresistance, high systemic toxicity, and low penetration of the blood brain barrier by many anticancer drugs contribute to the failure of anti-GBM therapies. To circumvent some of these obstacles, we tested a novel prodrug approach to evaluate anti-GBM efficacy by utilizing serum albumin-binding doxorubicin (Doxo), aldoxorubicin (Aldoxo), which is less toxic, is released from albumin in an acidic environment and accumulates in tumor tissues. A human GBM cell line that expresses a luciferase reporter (U87-luc) was stereotactically injected into the left striatum of the brain of immunodeficient mice. Following initial tumor growth for 12 days, mice were injected once a week in the tail-vein with Aldoxo [24 mg/kg or 18 mg/kg of doxorubicin equivalents-3/4 maximum tolerated dose (MTD)], Doxo [6 mg/kg (3/4 MTD)], or vehicle.
3.First-Line Aldoxorubicin vs Doxorubicin in Metastatic or Locally Advanced Unresectable Soft-Tissue Sarcoma: A Phase 2b Randomized Clinical Trial.
Chawla SP1, Papai Z2, Mukhametshina G3, Sankhala K4, Vasylyev L5, Fedenko A6, Khamly K7, Ganjoo K8, Nagarkar R9, Wieland S10, Levitt DJ10. JAMA Oncol. 2015 Dec;1(9):1272-80. doi: 10.1001/jamaoncol.2015.3101.
IMPORTANCE: Standard therapy for advanced soft-tissue sarcoma has not changed substantially in decades, and patient prognosis remains poor. Aldoxorubicin, a novel albumin-binding prodrug of doxorubicin, showed clinical activity against advanced soft-tissue sarcoma in phase 1 studies.
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