PTK2 protein tyrosine kinase 2
ENSG00000169398 · protein coding · Open Targets profile
Non-receptor protein-tyrosine kinase that plays an essential role in regulating cell migration, adhesion, spreading, reorganization of the actin cytoskeleton, formation and disassembly of focal adhesions and cell protrusions, cell cycle progression, cell proliferation and apoptosis. Required for early embryonic development and placenta development. Required for embryonic angiogenesis, normal cardiomyocyte migration and proliferation, and normal heart development. Regulates axon growth and neuronal cell migration, axon branching and synapse formation; required for normal development of the nervous system. Plays a role in osteogenesis and differentiation of osteoblasts. Functions in integrin signal transduction, but also in signaling downstream of numerous growth factor receptors, G protein-coupled receptors (GPCR), EPHA2, netrin receptors and LDL receptors. Forms multisubunit signaling complexes with SRC and SRC family members upon activation; this leads to the phosphorylation of additional tyrosine residues, creating binding sites for scaffold proteins, effectors and substrates. Regulates numerous signaling pathways. Promotes activation of phosphatidylinositol 3-kinase and the AKT1 signaling cascade. Promotes activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling cascade. Promotes localized and transient activation of guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs), and thereby modulates the activity of Rho family GTPases. Signaling via CAS family members mediates activation of RAC1. Phosphorylates NEDD9 following integrin stimulation (PubMed:9360983). Recruits the ubiquitin ligase MDM2 to P53/TP53 in the nucleus, and thereby regulates P53/TP53 activity, P53/TP53 ubiquitination and proteasomal degradation. Phosphorylates SRC; this increases SRC kinase activity. Phosphorylates ACTN1, ARHGEF7, GRB7, RET and WASL. Promotes phosphorylation of PXN and STAT1; most likely PXN and STAT1 are phosphorylated by a SRC family kinase that is recruited to autophosphorylated PTK2/FAK1, rather than by PTK2/FAK1 itself. Promotes phosphorylation of BCAR1; GIT2 and SHC1; this requires both SRC and PTK2/FAK1. Promotes phosphorylation of BMX and PIK3R1. Isoform 6 (FRNK) does not contain a kinase domain and inhibits PTK2/FAK1 phosphorylation and signaling. Its enhanced expression can attenuate the nuclear accumulation of LPXN and limit its ability to enhance serum response factor (SRF)-dependent gene transcription. {ECO:0000269|PubMed:10655584, ECO:0000269|PubMed:11331870, ECO:0000269|PubMed:11980671, ECO:0000269|PubMed:15166238, ECO:0000269|PubMed:15561106, ECO:0000269|PubMed:15895076, ECO:0000269|PubMed:16919435, ECO:0000269|PubMed:16927379, ECO:0000269|PubMed:17395594, ECO:0000269|PubMed:17431114, ECO:0000269|PubMed:17968709, ECO:0000269|PubMed:18006843, ECO:0000269|PubMed:18206965, ECO:0000269|PubMed:18256281, ECO:0000269|PubMed:18292575, ECO:0000269|PubMed:18497331, ECO:0000269|PubMed:18677107, ECO:0000269|PubMed:19138410, ECO:0000269|PubMed:19147981, ECO:0000269|PubMed:19224453, ECO:0000269|PubMed:20332118, ECO:0000269|PubMed:20495381, ECO:0000269|PubMed:21454698, ECO:0000269|PubMed:9360983}.
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
- Advanced Clinical, Structure with Ligand, High-Quality Ligand, High-Quality Pocket, Druggable Family
- Antibody
- UniProt loc med conf, GO CC med conf
- PROTAC
- Literature, UniProt Ubiquitination, Database Ubiquitination, Half-life Data, Small Molecule Binder
gnomAD loss of function constraint: o/e 0.2998799979686737 (upper bound 0.38447999954223633). 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 36 registry trials, updated in the last three years, of the most advanced drugs against PTK2 (defactinib, ifebemtinib, GSK-2256098), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- Rachel GrishamGOG Foundation · 4 of 4 trials Phase 2+
- Susana BanerjeeEuropean Network of Gynaecological Oncological Trial Groups (ENGOT) · 2 of 2 trials Phase 2+
- Alan HoMemorial Sloan Kettering Cancer Center · 1 of 1 trials Phase 2+
- Arsen OsipovCedar Sinai · 1 of 1 trials Phase 2+
- Carl DeSelmWashington University School of Medicine · 1 of 1 trials Phase 2+
- Christina WashingtonOU Health Stephenson Cancer Center · 1 of 1 trials Phase 2+
- Christine ParseghianM.D. Anderson Cancer Center · 1 of 1 trials Phase 2+
- Conor E SteuerEmory University Hospital/Winship Cancer Institute · 1 of 1 trials Phase 2+
- David M JackmanECOG-ACRIN Cancer Research Group · 1 of 1 trials Phase 2+
- Howard ColmanHuntsman Cancer Institute · 1 of 1 trials Phase 2+
- Juanita LopezNational Health Service, UK · 1 of 1 trials Phase 2+
- Keith T FlahertyECOG-ACRIN Cancer Research Group · 1 of 1 trials Phase 2+
- Matthew ReilleyUniversity of Virginia · 1 of 1 trials Phase 2+
- Patrick GriersonWashington University School of Medicine · 1 of 1 trials Phase 2+
- Priscilla BrastianosMassachusetts General Hospital · 1 of 1 trials Phase 2+
Registry trials of defactinib, ifebemtinib, GSK-2256098 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; 28 of 35 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. 1 trials list no sites and are left out. Source: ClinicalTrials.gov, fetched live.
10 trials of drugs against PTK2 were stopped early; 2 give no reason
Terminated, withdrawn and suspended interventional trials of defactinib, ifebemtinib, GSK-2256098, conteltinib, CEP-37440, PF-00562271, VS-4718, 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 10 most recent of 10.
- terminated · 2026-07-31 · Michael McHale · matched by the registry's drug synonyms“Due to loss of funding”
- terminated · 2025-07-15 · Thomas Jefferson University · Defactinib Hydrochloride“Trial enrollment was stopped early by study sponsors (before the anticipated accrual of 18 patients) due to no patients having significant reduction in disease.”
- terminated · 2024-02-20 · Verastem, Inc. · matched by the registry's drug synonyms“Company decided to discontinue trial to focus on development program next steps”
- withdrawn · 2020-11-17 · Raphael Bueno, MD · Defactinib“Funding complications coupled with competing scientific objectives”
- terminated · 2019-04-30 · Verastem, Inc. · matched by the registry's drug synonyms“The study was terminated upon completion of escalation phase, prior to opening expansion cohorts”
- terminated · 2017-07-28 · Verastem, Inc. · VS-4718“Sponsor's decision to deprioritize the program.”
- terminated · 2017-07-27 · Verastem, Inc. · Part B, Cohort 1- VS-4718, nab-paclitaxel, gemcitabine, Part A- VS-4718, nab-paclitaxel, gemcitabine“the company's decision to de-prioritize 4718 development”
- terminated · 2017-01-30 · Verastem, Inc. · defactinib (VS-6063)“Interim analysis-DSMB stated good safety profile but lack of efficacy”
- terminated · 2017-01-30 · Verastem, Inc. · matched by the registry's drug synonymsNo reason given
- withdrawn · 2017-01-27 · Verastem, Inc. · VS-4718No reason given
Paediatric incentives and obligations for PTK2's drugs
For defactinib, ifebemtinib, GSK-2256098, conteltinib, CEP-37440, PF-00562271, VS-4718: 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: yes · PTK2 is on the list. Membership alone neither requires nor waives a pediatric study.Rule: 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 · EMA/PE/0000245064 (avutometinib;defactinib, Treatment of ovarian cancer): W: decision granting a waiver in all age groups for all conditions or indications, 13 Jun 2025Rule: An EMA PIP decision (agreement, modification or waiver) lists the drug as its active substance, exact name. Source: EMA EMA/PE/0000245064, 2026-11-11
- EU orphan designation: yes · EU/3/25/3090 positive 18 Jul 2025: Treatment of ovarian cancer; EU/3/14/1429 positive 15 Jan 2015: Treatment of ovarian cancer; EU/3/13/1132 withdrawn 7 Jun 2013: Treatment of malignant mesotheliomaRule: 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 data download (dated snapshot), 2026-11-11
- Authorised in the EU: no · EMA lists no centrally authorised medicine of defactinib, ifebemtinib, gsk-2256098, conteltinib, cep-37440, pf-00562271, vs-4718Rule: 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 data download (dated snapshot), 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 defactinib, ifebemtinib, gsk-2256098, conteltinib, cep-37440, pf-00562271, vs-4718Rule: 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 · 3 interventional studies of defactinib, ifebemtinib, gsk-2256098, conteltinib, cep-37440, pf-00562271, vs-4718 include patients under 18; 2 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 7 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.