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Credit: Rhoda Baer
An experimental compound called TTT-3002 could be “one of the most potent FLT3 inhibitors to date,” according to researchers.
In preclinical experiments, TTT-3002 proved more active than the most potent FLT3 inhibitor currently in clinical trials.
TTT-3002 blocked FLT3 activity in human FLT3/ITD mutant leukemia cell lines, prolonged survival in a mouse model of FLT3-associated acute myeloid leukemia (AML), and proved toxic to leukemic cells from patients with AML.
Donald Small, MD, PhD, of Johns Hopkins University School of Medicine in Baltimore, and his colleagues reported these results in Blood.
“We’re very excited about TTT-3002, because it appears in our tests so far to be the most potent FLT3 inhibitor to date,” Dr Small said. “It showed activity against FLT3-mutated cells taken from patients and with minimal toxicity to normal bone marrow cells, making it a promising new candidate for the treatment of AML.”
In a series of experiments, the researchers found that the amount of TTT-3002 needed to block FLT3 activity in human leukemia cell lines was 6- to 7-fold lower than for ACC220, the most potent FLT3 inhibitor currently in clinical trials.
TTT-3002 also inhibited proteins made by genes further down the FLT3 signaling pathway, including STAT5, AKT, and MAPK. And it showed activity against the most frequently occurring FLT3 mutations, FLT3/ITD and FLT3/D835Y. (Many other inhibitors are ineffective against FLT3/D835Y mutations.)
When the researchers tested TTT-3002 in a mouse model of leukemia, they found the drug eliminated the presence of leukemic cells within 10 days of treatment.
Mice lived an average of more than 100 days after TTT-3002 treatment and resumed normal bone marrow activity. In comparison, mice treated with a placebo died an average of 18 days after treatment.
The researchers also found that TTT-3002 was toxic to leukemia samples taken from newly diagnosed and relapsed patients with AML, but it did not affect normal bone marrow cells taken from healthy donors.
A single dose of TTT-3002 caused more than 90% inhibition against FLT3 signaling that lasted for 12 hours. 
Credit: Rhoda Baer
An experimental compound called TTT-3002 could be “one of the most potent FLT3 inhibitors to date,” according to researchers.
In preclinical experiments, TTT-3002 proved more active than the most potent FLT3 inhibitor currently in clinical trials.
TTT-3002 blocked FLT3 activity in human FLT3/ITD mutant leukemia cell lines, prolonged survival in a mouse model of FLT3-associated acute myeloid leukemia (AML), and proved toxic to leukemic cells from patients with AML.
Donald Small, MD, PhD, of Johns Hopkins University School of Medicine in Baltimore, and his colleagues reported these results in Blood.
“We’re very excited about TTT-3002, because it appears in our tests so far to be the most potent FLT3 inhibitor to date,” Dr Small said. “It showed activity against FLT3-mutated cells taken from patients and with minimal toxicity to normal bone marrow cells, making it a promising new candidate for the treatment of AML.”
In a series of experiments, the researchers found that the amount of TTT-3002 needed to block FLT3 activity in human leukemia cell lines was 6- to 7-fold lower than for ACC220, the most potent FLT3 inhibitor currently in clinical trials.
TTT-3002 also inhibited proteins made by genes further down the FLT3 signaling pathway, including STAT5, AKT, and MAPK. And it showed activity against the most frequently occurring FLT3 mutations, FLT3/ITD and FLT3/D835Y. (Many other inhibitors are ineffective against FLT3/D835Y mutations.)
When the researchers tested TTT-3002 in a mouse model of leukemia, they found the drug eliminated the presence of leukemic cells within 10 days of treatment.
Mice lived an average of more than 100 days after TTT-3002 treatment and resumed normal bone marrow activity. In comparison, mice treated with a placebo died an average of 18 days after treatment.
The researchers also found that TTT-3002 was toxic to leukemia samples taken from newly diagnosed and relapsed patients with AML, but it did not affect normal bone marrow cells taken from healthy donors.
A single dose of TTT-3002 caused more than 90% inhibition against FLT3 signaling that lasted for 12 hours.
Credit: Rhoda Baer
An experimental compound called TTT-3002 could be “one of the most potent FLT3 inhibitors to date,” according to researchers.
In preclinical experiments, TTT-3002 proved more active than the most potent FLT3 inhibitor currently in clinical trials.
TTT-3002 blocked FLT3 activity in human FLT3/ITD mutant leukemia cell lines, prolonged survival in a mouse model of FLT3-associated acute myeloid leukemia (AML), and proved toxic to leukemic cells from patients with AML.
Donald Small, MD, PhD, of Johns Hopkins University School of Medicine in Baltimore, and his colleagues reported these results in Blood.
“We’re very excited about TTT-3002, because it appears in our tests so far to be the most potent FLT3 inhibitor to date,” Dr Small said. “It showed activity against FLT3-mutated cells taken from patients and with minimal toxicity to normal bone marrow cells, making it a promising new candidate for the treatment of AML.”
In a series of experiments, the researchers found that the amount of TTT-3002 needed to block FLT3 activity in human leukemia cell lines was 6- to 7-fold lower than for ACC220, the most potent FLT3 inhibitor currently in clinical trials.
TTT-3002 also inhibited proteins made by genes further down the FLT3 signaling pathway, including STAT5, AKT, and MAPK. And it showed activity against the most frequently occurring FLT3 mutations, FLT3/ITD and FLT3/D835Y. (Many other inhibitors are ineffective against FLT3/D835Y mutations.)
When the researchers tested TTT-3002 in a mouse model of leukemia, they found the drug eliminated the presence of leukemic cells within 10 days of treatment.
Mice lived an average of more than 100 days after TTT-3002 treatment and resumed normal bone marrow activity. In comparison, mice treated with a placebo died an average of 18 days after treatment.
The researchers also found that TTT-3002 was toxic to leukemia samples taken from newly diagnosed and relapsed patients with AML, but it did not affect normal bone marrow cells taken from healthy donors.
A single dose of TTT-3002 caused more than 90% inhibition against FLT3 signaling that lasted for 12 hours.