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New drug under test to treat lethal leukemia

Source: Xinhua    2018-04-12 01:58:37

WASHINGTON, April 11 (Xinhua) -- Albert Einstein College of Medicine researchers reported an experimental peptide drug that shows promise against the often-lethal cancer called acute myeloid leukemia (AML).

In a study published Wednesday in the journal Science Translational Medicine, they describe how the small protein drug works at the molecular level and the findings led to a Phase I/II clinical trial for patients with advanced AML and advanced myelodysplastic syndrome.

In preclinical studies, the experimental drug called ALRN-6924 tripled the median survival rate in an animal model of human AML (mice transplanted with human leukemia cells) from 50 to about 150 days.

"Most experimental drugs for leukemia achieve an increase in survival of only a few days in these preclinical models. Even more importantly, ALRN-6924 effectively cured about 40 percent of the treated mice," said the study leader Ulrich Steidl, professor of cell biology and medicine at Einstein.

AML is caused by damage to the DNA of blood-forming stem cells in the bone marrow, resulting in abnormal white blood cells, red blood cells, or platelets.

ALRN-6924 targets p53, a protein that suppresses tumors but is inactivated in many forms of cancer including AML, according to researchers.

The drug was designed to inhibit two naturally occurring proteins, MDMX and MDM2, whose overexpression inactivates p53, allowing cancer cells to multiply unchecked. The inhibitory effect was seen in both more mature AML cells and the immature stem cells that produce them.

"This is important," said Steidl, "because AML is driven by stem cells and if you don't target stem cells, the disease will come back very quickly."

ALRN-6924 is a so-called stapled alpha-helical peptide, a promising new class of drugs whose helical structure is stabilized using hydrocarbon "staples."

The stapling prevents the peptides from being degraded by enzymes before reaching their intended target, which often befalls conventional peptide drugs. ALRN-6924 is the first stapled peptide therapeutic to be tested in patients.

Editor: yan
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New drug under test to treat lethal leukemia

Source: Xinhua 2018-04-12 01:58:37

WASHINGTON, April 11 (Xinhua) -- Albert Einstein College of Medicine researchers reported an experimental peptide drug that shows promise against the often-lethal cancer called acute myeloid leukemia (AML).

In a study published Wednesday in the journal Science Translational Medicine, they describe how the small protein drug works at the molecular level and the findings led to a Phase I/II clinical trial for patients with advanced AML and advanced myelodysplastic syndrome.

In preclinical studies, the experimental drug called ALRN-6924 tripled the median survival rate in an animal model of human AML (mice transplanted with human leukemia cells) from 50 to about 150 days.

"Most experimental drugs for leukemia achieve an increase in survival of only a few days in these preclinical models. Even more importantly, ALRN-6924 effectively cured about 40 percent of the treated mice," said the study leader Ulrich Steidl, professor of cell biology and medicine at Einstein.

AML is caused by damage to the DNA of blood-forming stem cells in the bone marrow, resulting in abnormal white blood cells, red blood cells, or platelets.

ALRN-6924 targets p53, a protein that suppresses tumors but is inactivated in many forms of cancer including AML, according to researchers.

The drug was designed to inhibit two naturally occurring proteins, MDMX and MDM2, whose overexpression inactivates p53, allowing cancer cells to multiply unchecked. The inhibitory effect was seen in both more mature AML cells and the immature stem cells that produce them.

"This is important," said Steidl, "because AML is driven by stem cells and if you don't target stem cells, the disease will come back very quickly."

ALRN-6924 is a so-called stapled alpha-helical peptide, a promising new class of drugs whose helical structure is stabilized using hydrocarbon "staples."

The stapling prevents the peptides from being degraded by enzymes before reaching their intended target, which often befalls conventional peptide drugs. ALRN-6924 is the first stapled peptide therapeutic to be tested in patients.

[Editor: huaxia]
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