Aldoxorubicin (INNO-206) is a tumor-targeted doxorubicin conjugate in development by

CytRx CytRx Corp. () is a biopharmaceutical research and development oncology company based in Los Angeles, California. The CytRx oncology pipeline includes clinical trials involving their lead drug aldoxorubicin. Aldoxorubicin (formerly INNO-206) is ...

. Specifically, it is the (6- maleimido caproyl)

hydrazone Hydrazones are a class of organic compounds with the structure . They are related to ketones and aldehydes by the replacement of the oxygen =O with the = functional group. They are formed usually by the action of hydrazine on ketones or aldehydes. ...

doxorubicin Doxorubicin, sold under the brand name Adriamycin among others, is a chemotherapy medication used to treat cancer. This includes breast cancer, bladder cancer, Kaposi's sarcoma, lymphoma, and acute lymphocytic leukemia. It is often used togeth ...

. Essentially, this chemical name describes doxorubicin attached to an acid-sensitive linker (N-ε-maleimidocaproic acid

hydrazide Hydrazides in organic chemistry are a class of organic compounds with the formula RNHNH2 where R is acyl (R'CO-), sulfonyl (R'SO2-), or phosphoryl (R'2P(O)-). Unlike hydrazine and alkylhydrazines, hydrazides are nonbasic owing to the inductive infl ...

, or EMCH). The proposed mechanism of action is as follows: # After administration, aldoxorubicin rapidly binds endogenous circulating

albumin Albumin is a family of globular proteins, the most common of which are the serum albumins. All the proteins of the albumin family are water-soluble, moderately soluble in concentrated salt solutions, and experience heat denaturation. Albumins ...

through the EMCH linker. # Circulating albumin preferentially accumulates in tumors, bypassing uptake by other non-specific sites including heart, bone marrow and gastrointestinal tract. # Once albumin-bound aldoxorubicin reaches the tumor, the acidic environment of the tumor causes cleavage of the acid sensitive linker. # Free doxorubicin is released at the site of the tumor.

Clinical trials

Five phase I trials for safety characterization have been completed. Several phase II and III trials are underway.

Phase II

As of January 2017, there are 6

phase II clinical trial The phases of clinical research are the stages in which scientists conduct experiments with a health intervention to obtain sufficient evidence for a process considered effective as a medical treatment. For drug development, the clinical phases ...

s in progress: # Second-line therapy for patients with

glioblastoma Glioblastoma, previously known as glioblastoma multiforme (GBM), is one of the most aggressive types of cancer that begin within the brain. Initially, signs and symptoms of glioblastoma are nonspecific. They may include headaches, personality ch ...

# Treatment of HIV-positive patients with

Kaposi's sarcoma Kaposi's sarcoma (KS) is a type of cancer that can form masses in the skin, in lymph nodes, in the mouth, or in other organs. The skin lesions are usually painless, purple and may be flat or raised. Lesions can occur singly, multiply in a limite ...

# Combination therapy of

ifosfamide Ifosfamide (IFO), sold under the brand name Ifex among others, is a chemotherapy medication used to treat a number of types of cancer. This includes testicular cancer, soft tissue sarcoma, osteosarcoma, bladder cancer, small cell lung cancer, cer ...

and aldoxorubicin for treatment of metastatic or locally advanced sarcoma # Comparison of aldoxorubicin to the gold-standard treatment,

topotecan Topotecan, sold under the brand name Hycamtin among others, is a chemotherapeutic agent medication that is a topoisomerase inhibitor. It is a synthetic, water-soluble analog of the natural chemical compound camptothecin. It is used in the form o ...

, for metastatic

small cell lung cancer Small-cell carcinoma is a type of highly malignant cancer that most commonly arises within the lung, although it can occasionally arise in other body sites, such as the cervix, prostate, and gastrointestinal tract. Compared to non-small cell car ...

# Treatment of advanced or metastatic pancreatic ductal adenocarcinoma # Comparison of aldoxorubicin and

for patients with metastatic or locally advanced carcinoma

Phase III

A phase III trial for patients with relapsed soft tissue sarcoma comparing aldoxorubicin with several other chemotherapeutics is expected to complete in 2018. In November 2016, CytRx announced that preliminary results had been positive.

Clinical trials

Phase II

Phase III

References

Further reading