LCK LCK proto-oncogene, Src family tyrosine kinase
ENSG00000182866 · protein coding · Open Targets profile
Non-receptor tyrosine-protein kinase that plays an essential role in the selection and maturation of developing T-cells in the thymus and in the function of mature T-cells (PubMed:2470098). Plays a key role in T-cell antigen receptor (TCR)-linked signal transduction pathways (PubMed:2470098). Constitutively associated with the cytoplasmic portions of the CD4 and CD8 surface receptors (PubMed:2470098). Association of the TCR with a peptide antigen-bound MHC complex facilitates the interaction of CD4 and CD8 with MHC class II and class I molecules, respectively, thereby recruiting the associated LCK protein to the vicinity of the TCR-CD3 complex (PubMed:2470098). LCK then phosphorylates tyrosine residues within the immunoreceptor tyrosine-based activation motifs (ITAM) of the cytoplasmic tails of the TCR-gamma chains and CD3 subunits, initiating the TCR-CD3 signaling pathway (PubMed:2470098, PubMed:40592325). Once stimulated, the TCR recruits the tyrosine kinase ZAP70, that becomes phosphorylated and activated by LCK. Following this, a large number of signaling molecules are recruited, ultimately leading to lymphokine production. LCK also contributes to signaling by other receptor molecules. Associates directly with the cytoplasmic tail of CD2, which leads to hyperphosphorylation and activation of LCK. Also plays a role in the IL2 receptor-linked signaling pathway that controls the T-cell proliferative response. Binding of IL2 to its receptor results in increased activity of LCK. Is expressed at all stages of thymocyte development and is required for the regulation of maturation events that are governed by both pre-TCR and mature alpha beta TCR. Phosphorylates other substrates including RUNX3, PTK2B/PYK2, the microtubule-associated protein MAPT, RHOH or TYROBP. Interacts with FYB2 (PubMed:27335501). {ECO:0000269|PubMed:16339550, ECO:0000269|PubMed:16709819, ECO:0000269|PubMed:20028775, ECO:0000269|PubMed:20100835, ECO:0000269|PubMed:20851766, ECO:0000269|PubMed:21269457, ECO:0000269|PubMed:22080863, ECO:0000269|PubMed:2470098, ECO:0000269|PubMed:27335501, ECO:0000269|PubMed:38614099, ECO:0000269|PubMed:40592325}.
Each band is a group of drugs. It runs from the kind of drug on the left to the furthest stage that drug has reached in any disease on the right. Thicker bands mean more drugs.
Approved bands are highlighted. Withdrawn means the drug was pulled from the market or from development. A combined phase counts as the later one (Phase 1/2 is shown as Phase 2). Hover a band for the drug names. Source: Open Targets Platform, fetched live.
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
- Approved Drug, Structure with Ligand, High-Quality Ligand, High-Quality Pocket, Druggable Family
- Antibody
- UniProt loc high conf, GO CC high conf
- PROTAC
- Literature, UniProt Ubiquitination, Database Ubiquitination, Half-life Data, Small Molecule Binder
gnomAD loss of function constraint: o/e 0.21664999425411224 (upper bound 0.33869001269340515). Low values mean loss of function is poorly tolerated, a safety flag for inhibition.
Who runs trials of these drugs
Principal investigators and study chairs on 46 registry trials, updated in the last three years, of the most advanced drugs against LCK (pazopanib, ilorasertib, ENMD-981693, TG100-801), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- Aaron R WeissChildren's Oncology Group · 1 of 1 trials Phase 2+
- Alex MenziesMelanoma Institute Australia · 1 of 1 trials Phase 2+
- Alexander MusteaUniversity Hospital, Bonn · 1 of 1 trials Phase 2+
- Amado ZuritaM.D. Anderson Cancer Center · 1 of 1 trials Phase 2+
- Brian CostelloMayo Clinic · 1 of 1 trials Phase 2+
- Christelle De La FouchardièreCentre Léon Bérard, Lyon · 1 of 1 trials Phase 2+
- Christian F. MeyerJohns Hopkins University · 1 of 1 trials Phase 2+
- Christine CHEVREAUIUCT-O · 1 of 1 trials Phase 2+
- Christine LOVERACentre Antoine Lacassagne · 1 of 1 trials Phase 2+
- Emily K BergslandAlliance for Clinical Trials in Oncology · 1 of 1 trials Phase 2+
- Eric JonaschM.D. Anderson Cancer Center · 1 of 1 trials Phase 2+
- Esther BroekmanUniversity Medical Center Groningen · 1 of 1 trials Phase 2+
- Haitao WangTianjin Medical University Second Hospital · 1 of 1 trials Phase 2+
- ITALIANO AntoineInstitut Bergonié · 1 of 1 trials Phase 2+
- James GossageAugusta University · 1 of 1 trials Phase 2+
Registry trials of pazopanib, ilorasertib, ENMD-981693, TG100-801 updated in the last three years, counted by the country group of their listed sites. A trial with sites in several groups counts in each; 36 of 46 have all sites in one country.
Site counts are not patients per country, and trials registered only outside ClinicalTrials.gov are not covered. Where sites are is a fact about the record, not a judgement of its quality. Europe is the EU and EEA, the UK and Switzerland. Source: ClinicalTrials.gov, fetched live.
64 trials of drugs against LCK were stopped early; 9 give no reason
Terminated, withdrawn and suspended interventional trials of pazopanib, ilorasertib, ENMD-981693, TG100-801, JNJ-26483327, XL-228, newest update first, live from ClinicalTrials.gov. Each reason is quoted exactly as the registry gives it; we do not sort reasons into safety, efficacy or business. Dates are the last registry update. Showing the 25 most recent of 64.
- terminated · 2026-04-14 · Institut Claudius Regaud · Pazopanib“Slow recruitment rate”
- terminated · 2025-04-30 · University of Washington · Pazopanib hydrochloride“Study was terminated at completion of the Phase 1 dose escalation due to loss of financial support.”
- terminated · 2024-08-09 · Ludwig-Maximilians - University of Munich · Pazopanib, Placebo (for Pazopanib)“poor recruitment”
- terminated · 2023-07-17 · M.D. Anderson Cancer Center · Ilorasertib“Study terminated due to company's decision to discontinue drug development”
- terminated · 2022-09-28 · Rutgers, The State University of New Jersey · PazopanibNo reason given
- terminated · 2022-08-23 · National Cancer Institute (NCI) · Pazopanib, Pazopanib Hydrochloride“Interim monitoring”
- terminated · 2022-03-31 · Academic and Community Cancer Research United · Pazopanib Hydrochloride“Due to loss of funding from the private foundation source”
- terminated · 2022-03-22 · Heidelberg University · Pazopanib + Paclitaxel“Due to interim analysis' results and definitions fixed in protocol”
- terminated · 2021-10-28 · SCRI Development Innovations, LLC · Pazopanib“Based on analyses in Phase I, the study did not advance to Phase II.”
- terminated · 2021-09-22 · GWT-TUD GmbH · pazopanib or guideline conform chemotherapy“problems with recruiting”
- terminated · 2021-09-13 · M.D. Anderson Cancer Center · Pazopanib“PI request”
- terminated · 2021-09-08 · AIO-Studien-gGmbH · PazopanibNo reason given
- terminated · 2021-05-17 · The Christie NHS Foundation Trust · Pazopanib“Safety”
- terminated · 2021-04-13 · Emerald Clinical Inc. · pazopanib“low accrual”
- terminated · 2021-03-23 · Cliniques universitaires Saint-Luc- Université Catholique de Louvain · patients with sunitinib or pazopanib“not enough accrual”
- terminated · 2021-01-26 · Heidelberg University · pazopanib“slow recruitment”
- terminated · 2020-07-14 · Washington University School of Medicine · Pazopanib“Terminated by sponsor”
- terminated · 2020-02-13 · Cambridge University Hospitals NHS Foundation Trust · Pazopanib“Following DMC review, due to slow recruitment of evaluable patients.”
- terminated · 2019-10-24 · Virginia Commonwealth University · Pazopanib“Study drug no longer being clinically developed by manufacturer”
- terminated · 2019-10-09 · Novartis Pharmaceuticals · Pazopanib followed by everolimus“As the therapeutic landscape in renal cell carcinoma is changing, it has become apparent that information gained so far by CATChEz study is sufficient.”
- terminated · 2019-06-27 · The Netherlands Cancer Institute · pazopanib“stopping rule”
- terminated · 2018-11-14 · Fondazione IRCCS Istituto Nazionale dei Tumori, Milano · sunitinib or pazopanib“low enrolment”
- terminated · 2018-11-07 · Hellenic Cooperative Oncology Group · Gemcitabine-PazopanibNo reason given
- terminated · 2018-10-12 · The University of Texas Health Science Center, Houston · Pazopanib“Loss of laboratory performing molecular analysis”
- terminated · 2018-07-26 · University of Arizona · pazopanib hydrochloride“Slow accrual”
Paediatric incentives and obligations for LCK's drugs
For pazopanib, ilorasertib, ENMD-981693, TG100-801, JNJ-26483327, XL-228: what EMA and FDA publish about paediatric plans, orphan status and pediatric approvals, and how many registered studies take children. Each line is a yes, no or not published fact from the record linked under it; none of it is a forecast.
- FDA pediatric target list: no · LCK is not on the listRule: Target is on FDA's Pediatric Molecular Target List (relevant targets). Source: FDA Pediatric Molecular Target List (Listed as February 2026 on the FDA Pediatric Oncology page; the file served is 9.7.22_the_relevant_molecular_target_list.xlsx, whose Summary of Changes sheet is headed 'SEPTEMBER 2022 UPDATE' (footnote date 2022-09-01)), 2026-11-11
- EU paediatric investigation plan: yes · EMEA-000601-PIP01-09-M06 (pazopanib, Treatment of Ewing sarcoma family of tumours;Treatment of non-rhabdomyosarcoma soft tissue sarcoma;Treatment of rhabdomyosarcoma): PM: decision on the application for modification of an agreed PIP, 11 Sept 2019; compliance positive 24 Jul 2020Rule: An EMA PIP decision (agreement, modification or waiver) lists the drug as its active substance, exact name. Source: EMA EMEA-000601-PIP01-09-M06, 2026-11-11
- EU orphan designation: yes · EU/3/06/382 withdrawn 29 Jun 2006: Treatment of renal-cell carcinomaRule: An EU orphan designation lists the drug as its active substance (exact name) or belongs to a medicine that does; withdrawn and expired designations are listed with their status. Source: EMA EU/3/06/382, 2026-11-11
- Authorised in the EU: yes · Votrient: authorised since 14 Jun 2010Rule: An EMA medicine record lists the drug as its active substance or INN, exact name; national-only authorisations are not in this file. Source: EMA EPAR Votrient, 2026-11-11
- FDA orphan designation: not published · FDA's orphan designation database turns away automated requests, so this app does not read it; search it by hand at the linkRule: Would be: an FDA orphan designation names the drug. Source: FDA orphan designations search
- FDA pediatric oncology approval: no · FDA's table lists no pediatric approval of pazopanib, ilorasertib, enmd-981693, tg100-801, jnj-26483327, xl-228Rule: FDA's Pediatric Oncology Drug Approvals table names the drug. Source: FDA Pediatric Oncology Drug Approvals (content current as of 2026-03-03), 2026-11-11
- Registered studies open to children: yes · 22 interventional studies of pazopanib, ilorasertib, enmd-981693, tg100-801, jnj-26483327, xl-228 include patients under 18; 5 are recruiting, not yet recruiting or activeRule: The registry's age group includes Child (birth to 17 years), which also counts studies that set no minimum age. Source: ClinicalTrials.gov search, 2026-11-11
Rare pediatric disease voucher. FDA, content current as of 29 Apr 2026: “As of February 3, 2026, enactment of the Consolidated Appropriations Act, 2026, the rare pediatric disease PRV program will sunset after September 30, 2029. FDA may not award any PRVs under this program after September 30, 2029.” Voucher sale prices are not shown here; they appear only as company-reported news. FDA: Rare Pediatric Disease Designation and Priority Review Voucher Programs
All 8 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.