ABL1
ABL1 is the kinase half of the BCR::ABL1 fusion that causes chronic myeloid leukaemia. The CML drugs bind the ABL1 kinase domain, most in its ATP pocket and asciminib in a separate pocket that locks it shut.
Overview
ABL1 (chromosome 9q34.12) is a non-receptor tyrosine kinase in cytoskeletal remodelling, cell motility and adhesion, receptor endocytosis, autophagy, the DNA damage response and apoptosis; it phosphorylates regulators of actin dynamics such as WASF3, ANXA1, cortactin and ENAH and of adhesion such as BCAR1, CRK, CRKL, DOK1 and NEDD9 (UniProt P00519). The t(9;22) translocation fuses it to BCR, producing the constitutively active kinase of CML and Ph-positive ALL (bcr-abl1-signalling pathway). In OnCo the ABL1 kinase domain is what dasatinib (binding active and inactive conformations, inactive against T315I), ponatinib (a type II inhibitor whose triple bond accommodates the T315I gatekeeper) and asciminib (allosteric, locking ABL1 inactive through the myristoyl pocket, active against T315I at higher dose) bind; the BCR::ABL1 target page carries the fusion and the older inhibitors.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · ABL1 is the kinase half of the BCR::ABL1 fusion that causes chronic myeloid leukaemia. The CML drugs bind the ABL1 kinase domain, most in its ATP pocket and asciminib in a separate pocket that locks it shut.
- 1 · What it is
ABL1 is the kinase half of the BCR::ABL1 fusion that causes chronic myeloid leukaemia. The CML drugs bind the ABL1 kinase domain, most in its ATP pocket and asciminib in a separate pocket that locks it shut.
- 2 · What goes wrong in cancer
Asciminib's myristoyl-pocket mechanism is distinct from every ATP-site inhibitor, which is why it was approved for all newly diagnosed chronic-phase CML in 2024 and is being tested in Ph-positive ALL; dasatinib with blinatumomab can bring Ph-positive ALL into deep remission without chemotherapy (corpus drug records).
- 3 · How drugs use it
3 products aim at ABL1: small molecules. Kinases are switched on by binding ATP inside the cell, so most drugs are small molecules shaped to plug that ATP pocket.
External identifiers
Biology
Asciminib's myristoyl-pocket mechanism is distinct from every ATP-site inhibitor, which is why it was approved for all newly diagnosed chronic-phase CML in 2024 and is being tested in Ph-positive ALL; dasatinib with blinatumomab can bring Ph-positive ALL into deep remission without chemotherapy (corpus drug records).
- Chronic myeloid leukaemia (BCR::ABL1)
- Philadelphia-positive acute lymphoblastic leukaemia
Asciminib is a BCR::ABL1 blocker that binds a different pocket from every other TKI, approved for all newly diagnosed chronic myeloid leukaemia in 2024 and now being tested in Ph-positive ALL.
Dasatinib is a second-generation BCR::ABL1 pill that, combined with the immunotherapy blinatumomab, can put Ph-positive ALL into deep remission with no chemotherapy at all.
Ponatinib is the only BCR::ABL1 inhibitor that covers the T315I resistance mutation. In 2024 it became the preferred pill for newly diagnosed Ph-positive ALL.
Notes
top- Prevalence not recorded in this wave: HGNC and UniProt carry no positivity rates and no other source was consulted.
Latest papers
topQuery for this target: (TITLE:"ABL1" OR ABSTRACT:"ABL1" OR TITLE:"c-ABL" OR ABSTRACT:"c-ABL" OR TITLE:"ABL" OR ABSTRACT:"ABL" OR TITLE:"JTK7" OR ABSTRACT:"JTK7" OR TITLE:"ABL proto-oncogene 1, non-receptor tyrosine kinase" OR ABSTRACT:"ABL proto-oncogene 1, non-receptor tyrosine kinase") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about ABL1, not a curated reading list.
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