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AS1411

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AS1411 has shown activity against a wide range of solid and blood cancer cell lines in preclinical experiments and could therefore have potential against a variety of human cancers. Clinical development is focused on acute myeloid leukaemia (AML).

AS1411 is an aptamer. This is a type of drug based on a short piece of DNA or RNA. However, unlike some other drugs based on these chemicals, aptamers work as conventional drugs, binding to a protein target by virtue of a fit with its three-dimensional structure. The term aptamer is derived from the Greek ‘aptos’ (to fit).

AS1411 has a structure that allows it to bind specifically to a protein called nucleolin, which is found on the surface of many cancer cells. Once bound, the AS1411 aptamer is taken into the cancer cell, where it causes death by apoptosis (programmed cell death).

A previous phase I trial of AS1411 in 30 patients with various advanced cancers reported no serious adverse events related to treatment and promising signs of anti-cancer activity were seen.

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AML (acute myeloid leukaemia)

Studies have shown that blast cells from patients with AML are highly sensitive to AS1411, while normal B cells are unaffected by high doses of the drug. AML cell lines are also very sensitive to AS1411, and synergy (more than additive effects) have been seen when AS1411 is combined with cytarabine (Ara-C), a common current treatment for AML. A randomised phase II trial reported at ASCO 2009 showed that the addition of AS1411 to high-dose cytarabine increased response rates without significantly increasing side-effects in patients with relapsed or refractory AML.

AS1411 has been granted orphan drug status in both the United States and the European Union for the treatment of AML.

 

 

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