SRC SRC proto-oncogene, non-receptor tyrosine kinase
ENSG00000197122 · protein coding · Open Targets profile
Non-receptor protein tyrosine kinase which is activated following engagement of many different classes of cellular receptors including immune response receptors, integrins and other adhesion receptors, receptor protein tyrosine kinases, G protein-coupled receptors as well as cytokine receptors (PubMed:34234773). Participates in signaling pathways that control a diverse spectrum of biological activities including gene transcription, immune response, cell adhesion, cell cycle progression, apoptosis, migration, and transformation. Due to functional redundancy between members of the SRC kinase family, identification of the specific role of each SRC kinase is very difficult. SRC appears to be one of the primary kinases activated following engagement of receptors and plays a role in the activation of other protein tyrosine kinase (PTK) families. Receptor clustering or dimerization leads to recruitment of SRC to the receptor complexes where it phosphorylates the tyrosine residues within the receptor cytoplasmic domains. Plays an important role in the regulation of cytoskeletal organization through phosphorylation of specific substrates such as AFAP1. Phosphorylation of AFAP1 allows the SRC SH2 domain to bind AFAP1 and to localize to actin filaments. Cytoskeletal reorganization is also controlled through the phosphorylation of cortactin (CTTN) (Probable). When cells adhere via focal adhesions to the extracellular matrix, signals are transmitted by integrins into the cell resulting in tyrosine phosphorylation of a number of focal adhesion proteins, including PTK2/FAK1 and paxillin (PXN) (PubMed:21411625). In addition to phosphorylating focal adhesion proteins, SRC is also active at the sites of cell-cell contact adherens junctions and phosphorylates substrates such as beta-catenin (CTNNB1), delta-catenin (CTNND1), and plakoglobin (JUP). Another type of cell- cell junction, the gap junction, is also a target for SRC, which phosphorylates connexin-43 (GJA1). SRC is implicated in regulation of pre-mRNA-processing and phosphorylates RNA-binding proteins such as KHDRBS1 (Probable). Phosphorylates PKP3 at 'Tyr-195' in response to reactive oxygen species, which may cause the release of PKP3 from desmosome cell junctions into the cytoplasm (PubMed:25501895). Also plays a role in PDGF-mediated tyrosine phosphorylation of both STAT1 and STAT3, leading to increased DNA binding activity of these transcription factors (By similarity). Involved in the RAS pathway through phosphorylation of RASA1 and RASGRF1 (PubMed:11389730). Plays a role in EGF-mediated calcium-activated chloride channel activation (PubMed:18586953). Required for epidermal growth factor receptor (EGFR) internalization through phosphorylation of clathrin heavy chain (CLTC and CLTCL1) at 'Tyr-1477'. Involved in beta-arrestin (ARRB1 and ARRB2) desensitization through phosphorylation and activation of GRK2, leading to beta-arrestin phosphorylation and internalization. Has a critical role in the stimulation of the CDK20/MAPK3 mitogen-activated protein kinase cascade by epidermal growth factor (Probable). Might be involved not only in mediating the transduction of mitogenic signals at the level of the plasma membrane but also in controlling progression through the cell cycle via interaction with regulatory proteins in the nucleus (PubMed:7853507). Plays an important role in osteoclastic bone resorption in conjunction with PTK2B/PYK2. Both the formation of a SRC- PTK2B/PYK2 complex and SRC kinase activity are necessary for this function. Recruited to activated integrins by PTK2B/PYK2, thereby phosphorylating CBL, which in turn induces the activation and recruitment of phosphatidylinositol 3-kinase to the cell membrane in a signaling pathway that is critical for osteoclast function (PubMed:14585963, PubMed:8755529). Upon activation of the G(q)- dependent KISS1/KISS1R signaling pathway, active SRC is recruited, together with the phosphatase DUSP18, to the KISS1R C-terminus (PubMed:38346942). This leads to DUSP18-mediated SRC dephosphorylation and inactivation, down-regulation of osteoclast differentiation and activity, and consequently suppression of bone resorption (By similarity). Promotes energy production in osteoclasts by activating mitochondrial cytochrome C oxidase (PubMed:12615910). Phosphorylates DDR2 on tyrosine residues, thereby promoting its subsequent autophosphorylation (PubMed:16186108). Phosphorylates RUNX3 and COX2 on tyrosine residues, TNK2 on 'Tyr-284' and CBL on 'Tyr-731' (PubMed:20100835, PubMed:21309750). Enhances RIGI-elicited antiviral signaling (PubMed:19419966). Phosphorylates PDPK1 at 'Tyr-9', 'Tyr-373' and 'Tyr-376' (PubMed:14585963). Phosphorylates BCAR1 at 'Tyr-128' (PubMed:22710723). Phosphorylates CBLC at multiple tyrosine residues, phosphorylation at 'Tyr-341' activates CBLC E3 activity (PubMed:20525694). Phosphorylates synaptic vesicle protein synaptophysin (SYP) (By similarity). Involved in anchorage-independent cell growth (PubMed:19307596). Required for podosome formation (By similarity). Mediates IL6 signaling by activating YAP1-NOTCH pathway to induce inflammation-induced epithelial regeneration (PubMed:25731159). Phosphorylates OTUB1, promoting deubiquitination of RPTOR (PubMed:35927303). Phosphorylates caspase CASP8 at 'Tyr-380' which negatively regulates CASP8 processing and activation, down-regulating CASP8 proapoptotic function (PubMed:16619028). Mediates laminin-induced activation of RAC1 signaling through phosphorylation of syntrophin (By similarity). {ECO:0000250|UniProtKB:P05480, ECO:0000250|UniProtKB:Q9WUD9, ECO:0000269|PubMed:11389730, ECO:0000269|PubMed:12615910, ECO:0000269|PubMed:14585963, ECO:0000269|PubMed:16186108, ECO:0000269|PubMed:16619028, ECO:0000269|PubMed:18586953, ECO:0000269|PubMed:19307596, ECO:0000269|PubMed:19419966, ECO:0000269|PubMed:20100835, ECO:0000269|PubMed:20525694, ECO:0000269|PubMed:21309750, ECO:0000269|PubMed:21411625, ECO:0000269|PubMed:22710723, ECO:0000269|PubMed:25501895, ECO:0000269|PubMed:25731159, ECO:0000269|PubMed:34234773, ECO:0000269|PubMed:35927303, ECO:0000269|PubMed:38346942, ECO:0000269|PubMed:7853507, ECO:0000269|PubMed:8755529, ECO:0000269|PubMed:8759729, ECO:0000305|PubMed:11964124, ECO:0000305|PubMed:8672527, ECO:0000305|PubMed:9442882}.
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, Human Protein Atlas loc
- PROTAC
- Literature, UniProt Ubiquitination, Database Ubiquitination, Half-life Data, Small Molecule Binder
gnomAD loss of function constraint: o/e 0.20654000341892242 (upper bound 0.3283799886703491). 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 45 registry trials, updated in the last three years, of the most advanced drugs against SRC (bosutinib, vandetanib, tirbanibulin, saracatinib, ilorasertib, ENMD-981693, TG100-801), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- Alberto LecchiAlmirall, srl · 1 of 1 trials Phase 2+
- Annetine GelijnsData and Clinical Coordinating Center- InCHOIR · 1 of 1 trials Phase 2+
- Daniel J RenoufBCCA - Vancouver Cancer Centre, Vancouver BC, Canada · 1 of 1 trials Phase 2+
- Danielle Antin-OzerkisYale University · 1 of 1 trials Phase 2+
- Edward LainAustin Institute for Clinical Research · 1 of 1 trials Phase 2+
- Elias JabbourM.D. Anderson Cancer Center · 1 of 1 trials Phase 2+
- Elisabeth MW EekhoffAmsterdam University Medical Center · 1 of 1 trials Phase 2+
- Fabrice ANDREGustave Roussy, Villejuif · 1 of 1 trials Phase 2+
- Fabrice BARLESICHU Hopital Nord Marseille · 1 of 1 trials Phase 2+
- Fernando L PaganGeorgetown Univeristy · 1 of 1 trials Phase 2+
- Gary MiddletonRoyal Surrey County Hospital NHS Foundation Trust · 1 of 1 trials Phase 2+
- Gregory DowneyNational Jewish Health · 1 of 1 trials Phase 2+
- Haruhisa InoueKyoto University · 1 of 1 trials Phase 2+
- Henrik Hjorth-HansenSt. Olavs Hospital · 1 of 1 trials Phase 2+
- Javier Pinilla-IbarzH. Lee Moffitt Cancer Center and Research Institute · 1 of 1 trials Phase 2+
Registry trials of bosutinib, vandetanib, tirbanibulin, saracatinib, 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; 24 of 41 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. 4 trials list no sites and are left out. Source: ClinicalTrials.gov, fetched live.
47 trials of drugs against SRC were stopped early; 7 give no reason
Terminated, withdrawn and suspended interventional trials of bosutinib, vandetanib, tirbanibulin, saracatinib, ilorasertib, ENMD-981693, TG100-801, XL-228, JNJ-26483327, AZD-0424, 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 47.
- withdrawn · 2024-05-30 · Medical University of Graz · Tirbanibulin“lack of ressources”
- terminated · 2024-03-19 · Fundacion Espanola para la Curacion de la Leucemia Mieloide Cronica · Bosutinib 400 MG Monotherapy, Bosutinib 400 MG + Atezolizumab 840 MG in 14 ML Injection“The study has been prematurely terminated due to the onset of 2 dose limiting toxicities in 2 patients.”
- withdrawn · 2024-01-05 · Hoffmann-La Roche · Vandetanib“Due to several logistical challenges during start-up which could not be overcome study was withdrawn.”
- terminated · 2023-07-17 · M.D. Anderson Cancer Center · Ilorasertib“Study terminated due to company's decision to discontinue drug development”
- terminated · 2022-07-01 · Milton S. Hershey Medical Center · matched by the registry's drug synonyms“Product complaint”
- withdrawn · 2022-06-09 · City of Hope Medical Center · Bosutinib Monohydrate“Drug availability”
- terminated · 2021-12-30 · Pfizer · BosutinibNo reason given
- terminated · 2021-11-01 · Ronald Weigel · Vandetanib“Drugs unavailable”
- terminated · 2021-09-27 · Pfizer · Bosutinib“See termination reason in detailed description.”
- terminated · 2021-07-14 · H. Lee Moffitt Cancer Center and Research Institute · Vandetanib“Lack of efficacy”
- terminated · 2021-01-26 · National Cancer Institute (NCI) · Vandetanib, Vandetanib/Metformin“Vandetanib is no longer available as Sanofi has decided not to provide additional drug. All subjects are off-study.”
- terminated · 2020-11-19 · M.D. Anderson Cancer Center · Bosutinib“Terminated per PI's request at the time of CR. Study was closed due to low/slow accrual due to other competing studies.”
- terminated · 2020-07-30 · Baylor College of Medicine · saracatinibNo reason given
- terminated · 2020-05-11 · M.D. Anderson Cancer Center · Bosutinib“Terminated per PI's request due to competing priorities.”
- terminated · 2020-01-18 · Sarcoma Alliance for Research through Collaboration · Saracatinib“The Data Safety Monitoring Board (DSMB) recommended study termination for slow accrual and futility.”
- terminated · 2019-08-20 · National Cancer Institute (NCI) · saracatinib“The study was terminated after all enrolled participants progressed.”
- terminated · 2019-03-26 · Barbara Ann Karmanos Cancer Institute · matched by the registry's drug synonymsNo reason given
- terminated · 2018-11-29 · National Cancer Institute (NCI) · Vandetanib“Terminated due to slow accrual,primary endpoint reached \& investigator left NIH.”
- terminated · 2018-11-14 · M.D. Anderson Cancer Center · matched by the registry's drug synonyms“Sponsor withdrew support.”
- terminated · 2018-02-05 · Cancer Research UK · matched by the registry's drug synonyms“Single agent phase completed, insufficient supportive preclinical data to proceed with combination phase”
- withdrawn · 2017-04-24 · SWOG Cancer Research Network · vandetanib“Withdrawn because SWOG no longer pursuing this study at this time”
- terminated · 2017-02-07 · Stanford University · Vandetanib“Low accrual”
- terminated · 2016-12-21 · Genzyme, a Sanofi Company · vandetanib“Slow recruitment”
- terminated · 2016-12-05 · Genzyme, a Sanofi Company · ZD6474 (Vandetanib at the dose of 100 mg), Placebo to match ZD6474 (Vandetanib at the dose of 100 mg), ZD6474 (Vandetanib at the dose of 300 mg), Placebo to match ZD6474 (Vandetanib at the dose of 300 mg)No reason given
- terminated · 2016-10-10 · Genzyme, a Sanofi Company · Vandetanib“Recruitment stopped according to early stopping rule (by protocol)”
Paediatric incentives and obligations for SRC's drugs
For bosutinib, vandetanib, tirbanibulin, saracatinib, ilorasertib, ENMD-981693, TG100-801, XL-228, JNJ-26483327, AZD-0424: 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 · SRC 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-000727-PIP01-09-M07 (Bosutinib, Treatment of chronic myeloid leukaemia (CML)): PM: decision on the application for modification of an agreed PIP, 7 Aug 2023; compliance positive 15 Dec 2023; EMEA-000052-PIP01-07-M03 (vandetanib, Treatment of medullary thyroid carcinoma): PM: decision on the application for modification of an agreed PIP, 30 Nov 2013; compliance positive 20 Jun 2014Rule: An EMA PIP decision (agreement, modification or waiver) lists the drug as its active substance, exact name. Source: EMA data download (dated snapshot), 2026-11-11
- EU orphan designation: yes · EU/3/25/3194 positive 9 Jan 2026: Treatment of fibrodysplasia ossificans progressiva; EU/3/10/762 withdrawn 4 Aug 2010: Treatment of chronic myeloid leukaemia; EU/3/05/344 withdrawn 24 Jan 2006: Treatment of medullary thyroid 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 data download (dated snapshot), 2026-11-11
- Authorised in the EU: yes · Caprelsa: authorised since 16 Feb 2012; Klisyri: authorised since 16 Jul 2021; Bosulif: authorised since 27 Mar 2013; Zactima: application withdrawnRule: 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: yes · Bosutinib [Bosulif], 26 Sept 2023: Treatment of adult and pediatric patients 1 year of age and older with chronic phase (CP) Philadelphia chromosome-positive chronic myelogenous leukemia (Ph+ CML), newly-diagnosed or resistant or intolerant to prior therapyRule: FDA's Pediatric Oncology Drug Approvals table names the drug. Source: FDA Pediatric Oncology Drug Approvals (content current as of 2026-03-03), 2026-11-12
- Registered studies open to children: yes · 19 interventional studies of bosutinib, vandetanib, tirbanibulin, saracatinib, ilorasertib, enmd-981693, tg100-801, xl-228, jnj-26483327, azd-0424 include patients under 18; 4 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, 2026-11-12
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 11 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.