Past, present, and future of Bcr-Abl inhibitors: from chemical ...
2018年6月20日 · Bcr-Abl inhibitors paved the way of targeted therapy epoch. Imatinib was the first tyrosine kinase inhibitor to be discovered with high specificity for Bcr-Abl protein resulting from t (9, 22)-derived Philadelphia chromosome.
Imatinib: A Breakthrough of Targeted Therapy in Cancer
Imatinib, an oral targeted therapy, inhibits tyrosine kinases specifically BCR-ABL, c-KIT, and PDGFRA. Apart from its remarkable success in CML and GIST, Imatinib benefits various other tumors caused by Imatinib-specific abnormalities of PDGFR and c-KIT.
Imatinib in Chronic Myeloid Leukemia: an Overview - PMC
Imatinib was the first signal transduction inhibitor (STI), used in a clinical setting. It prevents a BCR-ABL protein from exerting its role in the oncogenic pathway in chronic myeloid leukemia (CML). Imatinib directly inhibits the constitutive tyrosine kinase activity.
The development of imatinib as a therapeutic agent for chronic …
2005年4月1日 · Mutations in the kinase domain (KD) of BCR-ABL that impair imatinib binding have been identified as the leading cause of resistance. Patients with CCR who achieve a profound reduction of BCR-ABL mRNA have a very low risk of disease progression.
Five-Year Follow-up of Patients Receiving Imatinib for Chronic …
2006年12月7日 · The cause of chronic myeloid leukemia (CML) is a constitutively active BCR-ABL tyrosine kinase. Imatinib inhibits this kinase, and in a short-term study was superior to interferon alfa plus ...
Second generation inhibitors of BCR-ABL for the treatment of imatinib …
More than 50 different BCR-ABL mutations have been identified in patients with imatinib-resistant CML and through random mutagenesis assays. Different imatinib-resistant BCR-ABL point mutants...
Targeted Therapy Drugs for Chronic Myeloid Leukemia
Imatinib (Gleevec) was the first drug to specifically target the BCR-ABL tyrosine kinase protein, and it’s sometimes the first drug tried in a person with CML. Most people with CML respond to treatment with imatinib, and these responses often last for many years.
The Ins and Outs of Bcr-Abl Inhibition - PMC - PubMed Central …
Nilotinib is a more potent (>20-fold) inhibitor of Bcr-Abl and exhibits activity towards the majority of imatinib-resistant mutations. 17,18 Nilotinib was developed from imatinib to incorporate alternative groups to N-methylpiperazine for binding Abl while retaining the elements to make hydrogen bonds with Glu286 and Asp381 . 17,38 As with ...
Targeted Therapy in the Treatment of Pediatric Acute …
2021年9月11日 · Imatinib is a first-generation ABL1 tyrosine kinase inhibitor with a molecular activity against BCR-ABL1, PDGFR, and c-KIT . The molecular mechanism of imatinib depends on the competitive inhibition of the ATP-active site by binding and changing its conformation, and thus preventing BCR-ABL1 autophosphorylation [ 30 ].
Long-Term Outcomes of Imatinib Treatment for Chronic Myeloid …
2017年3月9日 · Imatinib, a selective BCR-ABL1 kinase inhibitor, improved the prognosis for patients with chronic myeloid leukemia (CML). We conducted efficacy and safety analyses on the basis of...