Cell lines

Human multiple myeloma cell lines RPMI8226 and U266

Preparation method

Soluble in DMSO. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.

Reacting condition

0.27-2.16 mmol/L, 48 hours

Applications

INNO-206 inhibited blood vessel formation and reduced multiple myeloma cell growth in a pH-dependent fashion. In RPMI8226 cells, INNO-206 decreased cell viability in concentration-and pH-dependent manner. At pH5, INNO-206（≥0.54 mmol/L）essentially eliminated cell viability. In the MM1S cell line, INNO-206 inhibited cell growth in concentration and pH-dependent manner.

Animal models

Mice bearing the LAGk-1A tumor, multiple myeloma xenograft(LAGk-2) mouse model

Dosage form

Intravenous injection, 10.8 mg/kg; 3 times weekly at 1.8 mg/kg; once weekly at 5.4 mg/kg

Application

In mice bearing the LAGk-1A tumor, INNO-206 (10.8 mg/kg, once weekly, i.v.) showed significantly smaller tumor volumes and IgG levels on days 28, 35 and 42. In LAGk-2–bearing mice, treatment with INNO-206 (i.v. 3 times weekly at 1.8 mg/kg) significantly reduced tumor volume. INNO-206 (once weekly, 5.4 mg/kg) showed significantly smaller tumor volumes.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

Aldoxorubicin (INNO-206) is an albumin-binding prodrug of doxorubicin, which is released from albumin under acidic conditions. Aldoxorubicin (INNO-206) has potent antitumor activities in various cancer cell lines and in murine tumor models.

Aldoxorubicin (INNO-206) (0.27 to 2.16 μM) inhibits blood vessel formation and reduces multiple myeloma cell growth in a pH-dependent fashion[1].

Aldoxorubicin (INNO-206) (10.8 mg/kg, i.v.) shows significantly smaller tumor volumes and IgG levels on days 28, and is well tolerated with 90% of mice surviving until the termination of the study in the mice bearing the LAGκ-1A tumor[1]. Aldoxorubicin (INNO-206) shows a good safety profile at doses up to 260 mg/mL doxorubicin equivalents, and is able to induce tumor regressions in breast cancer, small cell lung cancer and sarcoma in phase I study[2]. Aldoxorubicin (INNO-206) shows superior activity over doxorubicin in a murine renal cell carcinoma model and in breast carcinoma xenograft models[3].

Reference：
[1]. Eric Sanchez, et al. Anti-Myeloma Effects of the Novel Anthracycline Derivative INNO-206. Clin Cancer Res.2012 18; 3856.
[2]. Kratz, F. INNO-206 (DOXO-EMCH), an Albumin-Binding Prodrug of Doxorubicin Under Development for Phase II Studies. Current Bioactive Compounds, 2011, 7(1): 33-38(6)
[3]. Graeser R, et al. INNO-206, the (6-maleimidocaproyl hydrazone derivative of doxorubicin), shows superior antitumor efficacy compared to doxorubicin in different tumor xenograft models and in an orthotopic pancreas carcinoma model. Invest New Drugs. 2010 F
[4]. Walker L, et al. Cell penetrating peptides fused to a thermally targeted biopolymer drug carrier improve the delivery and antitumor efficacy of an acid-sensitive doxorubicin derivative. Int J Pharm. 2012 Oct 15;436(1-2):825-32.