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Credit: Darren Baker
A handful of newly identified compounds may be able to treat chronic myelogenous leukemia (CML) more effectively than the tyrosine kinase inhibitors (TKIs) currently on the market, new research suggests.
Investigators identified 7 molecules that exhibited the potential to be more potent than approved TKIs.
Experiments suggested that 5 of the compounds—DB07107, DB06977, ST013616, DB04200, and ST007180—were more effective at inhibiting T315I-mutant BCR-ABL than wild-type BCR-ABL.
And 2 of them—ST019342 and DB01172—were effective only against mutant BCR-ABL.
Hemanth Naick Banavath, a PhD student at Pondicherry University-India, and his colleagues detailed these results in Nature: Scientific Reports.
To identify compounds to treat CML, the investigators screened several small molecule databases and docked against wild-type and drug-resistant T315I-mutant BCR-ABL.
The team also docked the TKIs ponatinib, bosutinib, bafetinib, dasatinib, nilotinib, and imatinib.
They identified 7 lead molecules—DB07107, DB06977, ST013616, DB04200, ST007180, ST019342, and DB01172—with better binding affinity and higher binding free energy than the TKIs.
Molecular dynamics simulations showed the dynamic behavior of protein-ligand complexes.
The protein backbone and ligand backbone of DB07107, DB06977, ST013616, DB04200, ST007180, and DB01172 were stable throughout the simulation period.
But the backbone of ST019342 showed anomalous fluctuations, and DB01172 showed instability with wild-type BCR-ABL.
A hydrogen bond analysis revealed that DB01172 has 6 hydrogens on average. However, in wild-type, it has 2 to 3 hydrogens on average. The investigators said this suggests low efficacy toward wild-type BCR-ABL.
Taking these findings together, the team said they cannot recommend ST019342 and DB01172 as potential treatments for CML.
On the other hand, they can endorse DB07107, DB06977, ST013616, DB04200, and ST007180, which showed “remarkable results.” 
Credit: Darren Baker
A handful of newly identified compounds may be able to treat chronic myelogenous leukemia (CML) more effectively than the tyrosine kinase inhibitors (TKIs) currently on the market, new research suggests.
Investigators identified 7 molecules that exhibited the potential to be more potent than approved TKIs.
Experiments suggested that 5 of the compounds—DB07107, DB06977, ST013616, DB04200, and ST007180—were more effective at inhibiting T315I-mutant BCR-ABL than wild-type BCR-ABL.
And 2 of them—ST019342 and DB01172—were effective only against mutant BCR-ABL.
Hemanth Naick Banavath, a PhD student at Pondicherry University-India, and his colleagues detailed these results in Nature: Scientific Reports.
To identify compounds to treat CML, the investigators screened several small molecule databases and docked against wild-type and drug-resistant T315I-mutant BCR-ABL.
The team also docked the TKIs ponatinib, bosutinib, bafetinib, dasatinib, nilotinib, and imatinib.
They identified 7 lead molecules—DB07107, DB06977, ST013616, DB04200, ST007180, ST019342, and DB01172—with better binding affinity and higher binding free energy than the TKIs.
Molecular dynamics simulations showed the dynamic behavior of protein-ligand complexes.
The protein backbone and ligand backbone of DB07107, DB06977, ST013616, DB04200, ST007180, and DB01172 were stable throughout the simulation period.
But the backbone of ST019342 showed anomalous fluctuations, and DB01172 showed instability with wild-type BCR-ABL.
A hydrogen bond analysis revealed that DB01172 has 6 hydrogens on average. However, in wild-type, it has 2 to 3 hydrogens on average. The investigators said this suggests low efficacy toward wild-type BCR-ABL.
Taking these findings together, the team said they cannot recommend ST019342 and DB01172 as potential treatments for CML.
On the other hand, they can endorse DB07107, DB06977, ST013616, DB04200, and ST007180, which showed “remarkable results.”
Credit: Darren Baker
A handful of newly identified compounds may be able to treat chronic myelogenous leukemia (CML) more effectively than the tyrosine kinase inhibitors (TKIs) currently on the market, new research suggests.
Investigators identified 7 molecules that exhibited the potential to be more potent than approved TKIs.
Experiments suggested that 5 of the compounds—DB07107, DB06977, ST013616, DB04200, and ST007180—were more effective at inhibiting T315I-mutant BCR-ABL than wild-type BCR-ABL.
And 2 of them—ST019342 and DB01172—were effective only against mutant BCR-ABL.
Hemanth Naick Banavath, a PhD student at Pondicherry University-India, and his colleagues detailed these results in Nature: Scientific Reports.
To identify compounds to treat CML, the investigators screened several small molecule databases and docked against wild-type and drug-resistant T315I-mutant BCR-ABL.
The team also docked the TKIs ponatinib, bosutinib, bafetinib, dasatinib, nilotinib, and imatinib.
They identified 7 lead molecules—DB07107, DB06977, ST013616, DB04200, ST007180, ST019342, and DB01172—with better binding affinity and higher binding free energy than the TKIs.
Molecular dynamics simulations showed the dynamic behavior of protein-ligand complexes.
The protein backbone and ligand backbone of DB07107, DB06977, ST013616, DB04200, ST007180, and DB01172 were stable throughout the simulation period.
But the backbone of ST019342 showed anomalous fluctuations, and DB01172 showed instability with wild-type BCR-ABL.
A hydrogen bond analysis revealed that DB01172 has 6 hydrogens on average. However, in wild-type, it has 2 to 3 hydrogens on average. The investigators said this suggests low efficacy toward wild-type BCR-ABL.
Taking these findings together, the team said they cannot recommend ST019342 and DB01172 as potential treatments for CML.
On the other hand, they can endorse DB07107, DB06977, ST013616, DB04200, and ST007180, which showed “remarkable results.”