STK11 serine/threonine kinase 11
ENSG00000118046 · protein coding · Open Targets profile
Tumor suppressor serine/threonine-protein kinase that controls the activity of AMP-activated protein kinase (AMPK) family members, thereby playing a role in various processes such as cell metabolism, cell polarity, apoptosis and DNA damage response (PubMed:12805220, PubMed:14517248, PubMed:14976552, PubMed:15016379, PubMed:15733851). Acts by phosphorylating the T-loop of AMPK family proteins, thus promoting their activity: phosphorylates PRKAA1, PRKAA2, BRSK1, BRSK2, MARK1, MARK2, MARK3, MARK4, NUAK1, NUAK2, SIK1, SIK2, SIK3 and SNRK but not MELK (PubMed:12805220, PubMed:14517248, PubMed:14976552, PubMed:15016379, PubMed:15733851). Also phosphorylates non-AMPK family proteins such as STRADA, PTEN and possibly p53/TP53 (PubMed:11430832, PubMed:15987703). Acts as a key upstream regulator of AMPK by mediating phosphorylation and activation of AMPK catalytic subunits PRKAA1 and PRKAA2 and thereby regulates processes including: inhibition of signaling pathways that promote cell growth and proliferation when energy levels are low, glucose homeostasis in liver, activation of autophagy when cells undergo nutrient deprivation, and B- cell differentiation in the germinal center in response to DNA damage (PubMed:14976552). Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton (PubMed:15016379). Required for cortical neuron polarization by mediating phosphorylation and activation of BRSK1 and BRSK2, leading to axon initiation and specification (PubMed:14976552). Involved in DNA damage response: interacts with p53/TP53 and recruited to the CDKN1A/WAF1 promoter to participate in transcription activation (PubMed:11430832, PubMed:17108107, PubMed:21317932). Able to phosphorylate p53/TP53; the relevance of such result in vivo is however unclear and phosphorylation may be indirect and mediated by downstream STK11/LKB1 kinase NUAK1 (PubMed:11430832, PubMed:17108107, PubMed:21317932). Also acts as a mediator of p53/TP53-dependent apoptosis via interaction with p53/TP53: translocates to the mitochondrion during apoptosis and regulates p53/TP53-dependent apoptosis pathways (PubMed:11430832, PubMed:17108107, PubMed:21317932). Regulates UV radiation-induced DNA damage response mediated by CDKN1A (PubMed:25329316). In association with NUAK1, phosphorylates CDKN1A in response to UV radiation and contributes to its degradation which is necessary for optimal DNA repair (PubMed:25329316). {ECO:0000269|PubMed:11430832, ECO:0000269|PubMed:12805220, ECO:0000269|PubMed:14517248, ECO:0000269|PubMed:14976552, ECO:0000269|PubMed:15016379, ECO:0000269|PubMed:15733851, ECO:0000269|PubMed:15987703, ECO:0000269|PubMed:17108107, ECO:0000269|PubMed:21317932, ECO:0000269|PubMed:25329316}.
Each row is a cancer, strongest overall evidence first. The two dots show how strong the inherited (germline) and tumour-mutation (somatic) evidence is; the line between them is the gap.
Scores run from 0 (no evidence) to 1 (strongest). A missing dot at 0 means Open Targets holds no evidence of that kind. Source: Open Targets Platform, fetched live.
Tractability
- Small molecule
- Structure with Ligand, High-Quality Ligand, Med-Quality Pocket, Druggable Family
- PROTAC
- Half-life Data, Small Molecule Binder
gnomAD loss of function constraint: o/e 0.1691100001335144 (upper bound 0.3051300048828125). Low values mean loss of function is poorly tolerated, a safety flag for inhibition.
Who runs trials of these drugs
No named investigators on registry trials of STK11's approved or late-stage drugs in the last three years.
No terminated, withdrawn or suspended trials of STK11's drugs are registered
All 0 drugs and clinical candidates as a table
Each drug, stage and indication links to its Open Targets record, where the trials and approvals behind it are listed. Salt forms (for example a mesylate) are listed as Open Targets records them, as separate entries.
| Drug | Type | Highest stage | Indications | Source records |
|---|---|---|---|---|
| No drugs or clinical candidates recorded. | ||||