Loading
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.
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.
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.
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.
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 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.
Broadly expressed or essential: HPA finds the RNA at low tissue specificity; the 3 medicines aimed at it (Asciminib, Dasatinib, Ponatinib) act on the wild-type protein, so normal tissue is exposed and the therapeutic window comes from the tumour's faster division or its dependence on the protein. HPA ABL1: RNA low tissue specificity; high antibody staining in 1 normal tissue; highest cancer staining carcinoid (1 of 4 high). Distribution: 1 cancer family in the corpus carries a prevalence row, label threshold or catalogue link for it (Leukaemia); Open Targets associates it with 7 specific cancer types at or above 0.5 (chronic myeloid leukemia, acute lymphoblastic leukemia, gastrointestinal stromal tumor, colorectal cancer, dermatofibrosarcoma protuberans, myelodysplastic/myeloproliferative disease and more); the corpus evidence decides and the Open Targets list is quoted for comparison. (Rule 7 of scripts/fetch-target-specificity.ts.)
Sources: Human Protein Atlas ABL1 tissue; Open Targets ENSG00000097007 associations
First described 1983. Earliest sequence paper UniProt cites for the protein: Groffen et al, Nature, 1983, "Homology between phosphotyrosine acceptor site of human c-abl and viral oncogene products". Source.
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).
RNA: low tissue specificity, detected in all normal tissues.
Medium: Adrenal gland, Breast, Bronchus, Cervix, Colon, Duodenum, Endometrium, Epididymis.
Medium only: breast cancer, cervical cancer, colorectal cancer, endometrial cancer.
HPA ABL1 tissue · HPA ABL1 pathology · HPA protein class: FDA approved drug targets
Human Protein Atlas version 25.1, antibody staining at reliability approved, enhanced or supported; used under CC BY-SA 3.0. Staining counts are patients per level in the atlas cohort, not population prevalence.
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.
Query 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.
Shares BCR::ABL1 (Philadelphia chromosome), Ponatinib, Chronic myeloid leukaemia (KEGG map), Chronic myeloid leukaemia, accelerated and blast phase and the tag wave5-target.
Shares Small-molecule kinase inhibitors and the tag wave5-target.
Shares Acute lymphoblastic leukaemia and the tag wave5-target.
Shares Acute lymphoblastic leukaemia and the tag wave5-target.
Shares Small-molecule kinase inhibitors and the tag wave5-target.
Shares Small-molecule kinase inhibitors and the tag wave5-target.
Shares Small-molecule kinase inhibitors and the tag wave5-target.
Shares Small-molecule kinase inhibitors and the tag wave5-target.