CXCR4 C-X-C motif chemokine receptor 4
ENSG00000121966 · protein coding · Open Targets profile
Receptor for the C-X-C chemokine CXCL12/SDF-1 that transduces a signal by increasing intracellular calcium ion levels and enhancing MAPK1/MAPK3 activation (PubMed:10074102, PubMed:10452968, PubMed:10644702, PubMed:10825158, PubMed:18799424, PubMed:20048153, PubMed:20505072, PubMed:24912431, PubMed:28978524, PubMed:8752280, PubMed:8752281). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors, such as adenylate cyclase (PubMed:16725153, PubMed:17197449, PubMed:18799424, PubMed:39093700). CXCR4 is coupled to G(i) G alpha proteins and mediates inhibition of adenylate cyclase (PubMed:17197449, PubMed:39093700). Involved in the AKT signaling cascade (PubMed:24912431). Plays a role in regulation of cell migration, e.g. during wound healing (PubMed:28978524). Also acts as a receptor for extracellular ubiquitin; leading to enhanced intracellular calcium ions and reduced cellular cAMP levels (PubMed:20228059). Binds bacterial lipopolysaccharide (LPS) et mediates LPS-induced inflammatory response, including TNF secretion by monocytes (PubMed:11276205). Involved in hematopoiesis and in cardiac ventricular septum formation (By similarity). Also plays an essential role in vascularization of the gastrointestinal tract, probably by regulating vascular branching and/or remodeling processes in endothelial cells (By similarity). Involved in cerebellar development; in the CNS, could mediate hippocampal-neuron surviva (By similarity). {ECO:0000250|UniProtKB:P70658, ECO:0000269|PubMed:10074102, ECO:0000269|PubMed:10452968, ECO:0000269|PubMed:10644702, ECO:0000269|PubMed:10825158, ECO:0000269|PubMed:11276205, ECO:0000269|PubMed:16725153, ECO:0000269|PubMed:17197449, ECO:0000269|PubMed:18799424, ECO:0000269|PubMed:20048153, ECO:0000269|PubMed:20228059, ECO:0000269|PubMed:20505072, ECO:0000269|PubMed:24912431, ECO:0000269|PubMed:28978524, ECO:0000269|PubMed:39093700, ECO:0000269|PubMed:8752280, ECO:0000269|PubMed:8752281}.
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 Withdrawn means the drug was pulled from the market or from development.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
- Advanced Clinical, UniProt loc high conf, GO CC high conf, UniProt SigP or TMHMM
- PROTAC
- UniProt Ubiquitination, Database Ubiquitination, Half-life Data, Small Molecule Binder
- Other modalities
- Advanced Clinical
gnomAD loss of function constraint: o/e 0.26809000968933105 (upper bound 0.5291399955749512). 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 72 registry trials, updated in the last three years, of the most advanced drugs against CXCR4 (mavorixafor, plerixafor, motixafortide, balixafortide, ulocuplumab, burixafor), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- Suk S De RavinNational Institute of Allergy and Infectious Diseases (NIAID) · 3 of 3 trials Phase 2+
- Anjulika Chawlabluebird bio, Inc. · 2 of 2 trials Phase 2+
- David H McDermottNational Institute of Allergy and Infectious Diseases (NIAID) · 2 of 2 trials Phase 2+
- Akshay SharmaSt. Jude Children's Research Hospital · 1 of 2 trials Phase 2+
- Dolores GrossoSidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University · 1 of 1 trials Phase 2+
- Douglas W SborovAlliance for Clinical Trials in Oncology · 1 of 1 trials Phase 2+
- Dung LeJohns Hopkins Medical Institution · 1 of 1 trials Phase 2+
- Elizabeth L BuddeCity of Hope Medical Center · 1 of 1 trials Phase 2+
- Fabio CiceriOspedale San Raffaele · 1 of 1 trials Phase 2+
- Franco LocatelliOspedale Pediatrico Bambino Gesù · 1 of 1 trials Phase 2+
- Gulam ManjiColumbia University · 1 of 1 trials Phase 2+
- Irini SeretiNational Institute of Allergy and Infectious Diseases (NIAID) · 1 of 1 trials Phase 2+
- James ShapiroUniversity of Alberta · 1 of 1 trials Phase 2+
- Jean - Antoine RIBEILHôpital Necker - Enfants Malades, Public Hospitals of Paris · 1 of 1 trials Phase 2+
- Ji Hyun LeeMagenta Therapeutics · 1 of 1 trials Phase 2+
Registry trials of mavorixafor, plerixafor, motixafortide, balixafortide, ulocuplumab, burixafor 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; 63 of 69 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. 3 trials list no sites and are left out. Source: ClinicalTrials.gov, fetched live.
47 trials of drugs against CXCR4 were stopped early; 5 give no reason
Terminated, withdrawn and suspended interventional trials of mavorixafor, plerixafor, motixafortide, balixafortide, ulocuplumab, burixafor, CTCE-9908, MSX-122, 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.
- terminated · 2025-07-25 · Ensoma · Plerixafor“This study was voluntarily terminated due to a business decision not to proceed, and not due to any safety issue.”
- withdrawn · 2025-06-22 · Minovia Therapeutics Ltd. · matched by the registry's drug synonyms“No recruitment”
- terminated · 2024-11-06 · Ensoma · Plerixafor“This study was voluntarily terminated due to a business decision not to proceed and not due to any safety issue”
- terminated · 2024-09-05 · BioLineRx, Ltd. · matched by the registry's drug synonyms“Due to lack of enrollment”
- terminated · 2024-05-17 · Fred Hutchinson Cancer Center · Plerixafor“Study ended early due to end of funding.”
- terminated · 2024-05-03 · Dana-Farber Cancer Institute · Ulocuplumab“Sponsor decision to end follow-up early”
- terminated · 2024-04-12 · Children's Hospital Medical Center, Cincinnati · matched by the registry's drug synonyms“Sponsor decision due to funding”
- terminated · 2023-11-01 · Jonsson Comprehensive Cancer Center · Plerixafor“slow accrual”
- terminated · 2023-11-01 · Spexis AG · Balixafortide“The study was halted early due to failure to meet the primary endpoint.”
- withdrawn · 2023-04-10 · 4Living Biotech · Plerixafor 20 MG/ML [Mozobil]“No participants Enrolled”
- withdrawn · 2023-04-07 · St. Jude Children's Research Hospital · Plerixafor“The safety and efficacy of plerixafor in adult and pediatric SCD patients was an unknown when we started. A lot more data from therapeutic trials is available. We feel that recruiting patients without a therapeutic option isn't ethically justifiable.”
- withdrawn · 2023-03-20 · MedSIR · matched by the registry's drug synonyms“Funder decision”
- terminated · 2023-01-30 · Dana-Farber Cancer Institute · Plerixafor“Slow accrual and futility”
- terminated · 2022-12-29 · X4 Pharmaceuticals · matched by the registry's drug synonyms“Due to low enrollment, the study was terminated early.”
- withdrawn · 2022-10-14 · Albert Einstein College of Medicine · matched by the registry's drug synonyms“Study withdrawn before any participants could be enrolled. Issues being able to effectively recruit participants into the study.”
- terminated · 2022-05-18 · Fred Hutchinson Cancer Center · Plerixafor“Terminated due to loss in funding.”
- terminated · 2021-09-16 · Bristol-Myers Squibb · matched by the registry's drug synonyms“Business objectives have changed, slow accrual, the standard of care for the patient population changed and we were unable to accrue any longer.”
- terminated · 2021-06-18 · CSL Behring · matched by the registry's drug synonyms“Unanticipated delays, not for safety reasons”
- terminated · 2021-05-19 · Reproductive Medicine Associates of New Jersey · matched by the registry's drug synonyms“low enrollment”
- terminated · 2020-10-20 · Washington University School of Medicine · matched by the registry's drug synonyms“Toxicity. Only enrolled patients in phase I portion of trial.”
- withdrawn · 2020-09-07 · Massachusetts General Hospital · matched by the registry's drug synonyms“Funding Withdrawn”
- withdrawn · 2020-07-24 · Jonsson Comprehensive Cancer Center · Plerixafor“No Participants Enrolled”
- terminated · 2020-03-02 · Weill Medical College of Cornell University · Plerixafor“terminated due to slow accrual”
- terminated · 2019-12-19 · Gian Paolo Fadini · Plerixafor“Safety reasons”
- withdrawn · 2019-12-11 · University of Maryland, Baltimore · Plerixafor“subject recruitment not feasible due to standard care changes”
Paediatric incentives and obligations for CXCR4's drugs
For mavorixafor, plerixafor, motixafortide, balixafortide, ulocuplumab, burixafor, CTCE-9908, MSX-122: 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 · CXCR4 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 · EMEA-002490-PIP01-18 (mavorixafor, Treatment of WHIM (warts, hypogammaglobulinemia, infections, and myelokathexis) syndrome): P: decision agreeing on a investigation plan, with or without partial waiver(s) and or deferral(s), 23 May 2024; EMEA-002718-PIP02-20 (balixafortide, Treatment of breast cancer): W: decision granting a waiver in all age groups for all conditions or indications, 12 Aug 2020; EMEA-000174-PIP01-07-M03 (Plerixafor, Myelosuppression caused by chemotherapy to treat malignant disorders, which requires an autologous haematopoietic stem cell transplant): PM: decision on the application for modification of an agreed PIP, 29 Oct 2013; compliance positive 26 Jan 2018Rule: 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/3/19/2183 positive 25 Jul 2019: Treatment of WHIM syndrome; EU/3/24/2899 positive 19 Feb 2024: Treatment of acute respiratory distress syndrome (ARDS); EU/3/23/2885 positive 12 Jan 2024: Treatment of patients undergoing haematopoietic stem cell transplantation; EU/3/04/227 expired 20 Oct 2004: Treatment to mobilize progenitor cells prior to stem cell transplantation; +4 moreRule: 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 · Xolremdi: authorised since 27 Apr 2026, orphan medicine, exceptional circumstances; Plerixafor Accord: authorised since 16 Dec 2022; Mozobil: authorised since 30 Jul 2009Rule: 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 mavorixafor, plerixafor, motixafortide, balixafortide, ulocuplumab, burixafor, ctce-9908, msx-122Rule: 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 · 40 interventional studies of mavorixafor, plerixafor, motixafortide, balixafortide, ulocuplumab, burixafor, ctce-9908, msx-122 include patients under 18; 11 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.