Protein / target

C-X-C chemokine receptor type 4

Encoded byCXCR4P61073Homo sapiensSwiss-Prot

UniProt: P61073 Ensembl: ENSG00000121966 HGNC: HGNC:2561 NCBI Gene: 7852

Clinically validated

Therapeutic maturity

Approved medicines

Open Targets target-level

View by indication →

Clinical trials

Small-molecule tractable

Druggability

Approved Drug

Protein at a glance

Biological role

C-X-C motif chemokine 12 receptor

Strongest disease association

WHIM syndrome

Via encoding gene CXCR4 · Genetic evidence · score 0.87

Therapeutic position

Established drug target

Small molecules and antibodies

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function overview

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.

View complete UniProt function annotation

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)

Subcellular location

Cell membraneCell junctionEarly endosomeLate endosomeLysosome

Domains and Gene Ontology detail (45)

Gene Ontology

Canchoring junction
Ccell leading edge
Ccell surface
Ccytoplasm
Ccytoplasmic vesicle
Cearly endosome
Cexternal side of plasma membrane
Cextracellular exosome
Clate endosome
Clysosome
Cplasma membrane
Cprotein-containing complex

352 aa · 40 kDa · 2 isoforms

Biological roles

Reactome v97

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Cell migrationUniProt · GOCell proliferation & survivalUniProtImmune signallingUniProt · GOCell adhesionUniProt · GOG protein-coupled signallingGO

View supporting evidence

Cell migration

·Receptor for the C-X-C chemokine CXCL12/SDF-1 that transduces a signal by increasing int…
·cell chemotaxis
·dendritic cell chemotaxis
·positive regulation of cell migration

Cell proliferation & survival

·Receptor for the C-X-C chemokine CXCL12/SDF-1 that transduces a signal by increasing int…

Immune signalling

·Receptor for the C-X-C chemokine CXCL12/SDF-1 that transduces a signal by increasing int…
·cellular response to cytokine stimulus
·immune response
·inflammatory response

Cell adhesion

·Cell junction
·regulation of cell adhesion

G protein-coupled signalling

·G protein-coupled receptor activity
·adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway
·G protein-coupled receptor signaling pathway

View underlying pathways (7)

Binding and entry of HIV virion

Signaling by ROBO receptors

Chemokine receptors bind chemokines

G alpha (i) signalling events

Formation of definitive endoderm

Specification of primordial germ cells

Developmental Lineage of Multipotent Pancreatic Progenitor Cells

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Interaction neighbourhood

STRING v12.0

Proteins with the strongest functional or physical association. Node size and line weight reflect STRING confidence; hover or select a partner to inspect one association.

10 strongest partners — larger node and heavier line mean higher confidence

Functional and physical associations from STRING v12.0. Only associations with this protein are drawn — partner-to-partner links are not part of this evidence.

Approved medicines with mapped indications

2 medicines · 4 areas

Approved therapies targeting this protein, grouped by what they are approved to treat — the disease-first view of the medicines below. Relationships come from the canonical approved-indication graph (ChEMBL phase-4), the same source as the drug cards.

Lymphoma1 medicine

plerixafor

Lymphoma, Non-Hodgkin's1 medicine

plerixafor

Multiple Myeloma1 medicine

plerixafor

Neoplasms2 medicines

mavorixafor plerixafor

3 medicines meet Open Targets' target-level approved-medicine definition; the 2 shown here are those on this page with a canonical approved disease indication in the graph. Approved indications from ChEMBL (phase-4), via the canonical drug→disease graph.

Drugs targeting this protein

How approved and investigational drugs engage this protein — mechanism and action type, direct vs complex targeting, and how broadly each acts across other targets. A drug-first view (the section above groups the approved ones disease-first); direct binders with few recorded targets are listed first.

plerixafor

Narrow target profileApprovedPartial agonist

C-X-C chemokine receptor type 4 partial agonist

Indicated for Lymphoma, Lymphoma, Non-Hodgkin's, Multiple Myeloma, Neoplasms

Direct interaction with this protein · Only this protein recorded as a target

mavorixafor

Narrow target profileApprovedAntagonist

C-X-C chemokine receptor type 4 antagonist

Indicated for Neoplasms

Direct interaction with this protein · Only this protein recorded as a target

ChEMBL mechanism, action type, target identity and approved indications. Open Targets clinical status.

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene CXCR4

Gene-level evidence surfaced through the gene CXCR4that encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

WHIM syndrome

0.94Well supported

Genetic evidence dominant · Open Targets 0.80

WHIM syndrome 1

0.89Well supported

Genetic evidence dominant · Open Targets 0.77

Multiple Myeloma

0.80Well supported

Clinical evidence dominant · Open Targets 0.66

Lymphoma

0.70Moderately supported

Clinical evidence dominant · Open Targets 0.52

Lymphoma, Non-Hodgkin's

0.69Moderately supported

Clinical evidence dominant · Open Targets 0.55

View evidence synthesis (5)

WHIM syndromeWell supported

0.94

agreement 0.84–1.00

Genetic57%Clinical28%Animal model9%Literature7%Genetic literaturedup

Open Targets aggregate 0.80 · 4 independent evidence families · 1 not counted as duplicate

WHIM syndrome 1Well supported

0.89

agreement 0.79–0.99

Genetic79%Animal model15%Clinical6%Literature0%Genetic literaturedup

Open Targets aggregate 0.77 · 4 independent evidence families · 1 not counted as duplicate

Multiple MyelomaWell supported

0.80

agreement 0.68–0.92

Clinical67%Somatic mutation25%Literature7%

Open Targets aggregate 0.66 · 3 independent evidence families

LymphomaModerately supported

0.70

agreement 0.58–0.82

Clinical61%Somatic mutation24%Literature15%

Open Targets aggregate 0.52 · 3 independent evidence families

Lymphoma, Non-Hodgkin'sModerately supported

0.69

agreement 0.54–0.85

Clinical85%Literature15%

Open Targets aggregate 0.55 · 2 independent evidence families

The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the per-type scores above show the calculation.

Show all associations

WHIM syndrome0.80

WHIM syndrome 10.77

Multiple Myeloma0.66

HIV Infections0.56

Lymphoma, Non-Hodgkin's0.55

Neoplasms0.54

Lymphoma0.52

Severe congenital neutropenia0.46

Precursor Cell Lymphoblastic Leukemia-Lymphoma0.43

Skin Neoplasms0.40

Drug development

8 compounds recorded · 3 approved · 5 in clinical development

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines. Distinct from the 2 drugs that target this protein in Forefront's canonical graph (2 with a mapped approved indication, shown above): these count different sets and are not a subset relation.

View all recorded compounds (8)

BURIXAFORPhase 2

MAVORIXAFORApproval

PLERIXAFORApproval

MSX-122Phase 1

MOTIXAFORTIDEApproval

BALIXAFORTIDEPhase 3

CTCE-9908Phase 1 2

ULOCUPLUMABPhase 3

Open Targets known-drugs universe. Drug name and highest clinical stage only — the disease relationship is NOT read from this slice (it carries trial-context noise); approved indications come from the canonical graph above.

Tractability

Small molecules — Strong

Approved Drug and Structure with Ligand support this modality.

Antibodies — Strong

Advanced Clinical and UniProt loc high conf support this modality.

Protein degraders — Emerging

Feasibility evidence (uniprot ubiquitination and database ubiquitination) — no clinical-stage drug of this modality recorded.

Other modalities — Strong

Advanced Clinical support this modality.

View underlying tractability evidence (14)

SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · High-Quality PocketSM · Druggable FamilyAB · Advanced ClinicalAB · UniProt loc high confAB · GO CC high confAB · UniProt SigP or TMHMMPR · UniProt UbiquitinationPR · Database UbiquitinationPR · Half-life DataPR · Small Molecule BinderOC · Advanced Clinical

Raw Open Targets tractability assessment buckets, by modality.

Clinical trials

Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein. Ranked by active status, then clinical phase and recency, and spread across the targeting drugs.

A Phase 3, Randomized, Double-blind, Placebo-controlled, Multicenter Study of Mavorixafor in Participants With Congenital and Acquired Primary Autoimmune and Idiopathic Chronic Neutropenic Disorders Who Are Experiencing Recurrent and/or Serious InfectionsPHASE3

RECRUITING · via mavorixafor · NCT06056297

Quadruplet Induction Followed by Teclistamab Consolidation and Doublet Maintenance in Patients With Primary Plasma Cell Leukemia: The QUANTUM TrialPHASE2

NOT_YET_RECRUITING · via plerixafor · NCT07605416

A Prospective Trial Evaluating Plerixafor-based Mobilization and Risk of Engraftment Syndrome After Autologous Hematopoietic Stem Cell TransplantationPHASE2

RECRUITING · via plerixafor · NCT07188090

Phase 1/2 Base-Edited Hematopoietic Stem/Progenitor Cell X-Linked Severe Combined Immunodeficiency Gene TherapyPHASE1/PHASE2

ENROLLING_BY_INVITATION · via plerixafor · NCT06851767

View all trials (26)

Allogeneic Hematopoietic Stem Cell Transplant for Patients With High Risk Hemoglobinopathies and Other Red Cell Transfusion Dependent DisordersPHASE2

RECRUITING · via plerixafor · NCT06872333

A Phase I/II Pilot Study of Memory-like NK Cells to Consolidate TCRαβ T Cell Depleted Haploidentical Transplant in High-risk AMLPHASE1/PHASE2

RECRUITING · via plerixafor · NCT06158828

Pre-transplant Purging and Post-transplant MRD-guided Maintenance Therapy With Elranatamab in Patients With High-risk Multiple MyelomaPHASE2

RECRUITING · via plerixafor · NCT06207799

Phase 1/2 Trial of Base Editing for Mutation Repair in Hematopoietic Stem & Progenitor Cells for X-linked Chronic Granulomatous DiseasePHASE1/PHASE2

RECRUITING · via plerixafor · NCT06325709

A Phase I/II Trial of Allogeneic Reduced-Intensity, HLA-Haploidentical Allogeneic Hematopoietic Cell Transplantation Followed by GVHD Prophylaxis With Cyclophosphamide, Bortezomib and Maraviroc for Hematologic Malignancies in People Living With HIV (PLWH)PHASE1/PHASE2

RECRUITING · via plerixafor · NCT05470491

Addition of JSP191 (C-kit Antibody) to Non-myeloablative Hematopoietic Cell Transplantation For Sickle Cell Disease and Beta-ThalassemiaPHASE1/PHASE2

ACTIVE_NOT_RECRUITING · via plerixafor · NCT05357482

A Multicentric, Exploratory, Non-randomised, Non-controlled, Prospective, Open-label Phase II Study Evaluating Safety and Efficacy of IBU, G-CSF and Plerixafor as Stem Cell Mobilization Regimen in Patients Affected by X-CGDPHASE2

RECRUITING · via plerixafor · NCT03055247

A Multi-center Randomized Phase II Study of the Impact of CD34+ Cell Dose on Absolute Lymphocyte Count Following High-Dose Therapy and Autologous Stem Cell Transplantation for Relapsed and Refractory Diffuse Large B-cell Lymphoma (DLBCL)PHASE2

ACTIVE_NOT_RECRUITING · via plerixafor · NCT02570542

Hematopoietic Stem Cell Mobilization in Idiopathic CD4 Lymphocytopenia Patients and Healthy Controls for the Study of T Cell Maturation and Trafficking in Murine ModelsPHASE2

RECRUITING · via plerixafor · NCT02015013

Phase I/II Study of Cellular Immunotherapy Using Central Memory-Enriched CD8+ T Cells Lentivirally Transduced to Express A CD19-Specific Chimeric Immunoreceptor Following Peripheral Blood Stem Cell Transplantation for Patients With High-Risk Intermediate Grade B-Lineage Non-Hodgkin LymphomaPHASE1/PHASE2

ACTIVE_NOT_RECRUITING · via plerixafor · NCT01318317

A Phase I Study of MozobilTM in the Treatment of Patients With WHIMSPHASE1/PHASE2

RECRUITING · via plerixafor · NCT00967785

Stem Cell Mobilization and Apheresis for Life-threatening Blood DisordersPHASE1

NOT_YET_RECRUITING · via plerixafor · NCT07585136

St. Jude Autologous Genome Edited Stem Cells For Sickle Cell Disease-1PHASE1

RECRUITING · via plerixafor · NCT06506461

Protocol Title: Safety and Feasibility of Autologous CD34+ Hematopoietic Stem Cells Mobilization and Apheresis in Participants With RUNX1 Familial Platelet DisorderPHASE1

RECRUITING · via plerixafor · NCT06414889

Bone Marrow Derived Stem Cells Mobilization for Treatment of Asherman's Syndrome, Atrophic Endometrium, and Recurrent Implantation FailureEARLY_PHASE1

RECRUITING · via plerixafor · NCT05343572

Phase 1 Trial for Patients With Advanced Hematologic Malignancies Undergoing Reduced Intensity Allogeneic HCT With a T-cell Depleted Graft With Infusion of Conventional T-cells and Regulatory T-cellsPHASE1

ACTIVE_NOT_RECRUITING · via plerixafor · NCT05088356

A Pilot Study To Evaluate The Safety And Feasibility of Hematopoietic Progenitor Cell Mobilization With Plerixafor as Part of a Gene Therapy Strategy in Sickle Cell DiseasePHASE1

ACTIVE_NOT_RECRUITING · via plerixafor · NCT03664830

GCSF Plus Plerixafor as First-line Treatment for Autologous Stem Cells Harvest in Children With Malignant Diseases in Need for High-dose Chemotherapy With Stem Cell Rescue.PHASE4

UNKNOWN · via plerixafor · NCT02006225

Mobilization Test of BM Progenitor Cells With Plerixafor / AMD3100: Controlled Parallel Group Comparison Between Diabetic and Non Diabetic SubjectsPHASE4

COMPLETED · via plerixafor · NCT02056210

A Phase 4, Multicenter, Randomized, Comparator Trial Evaluating the Standard Weight-Based Dose (0.24 mg/kg) Compared to a Fixed Dose (20 mg) of Plerixafor Injection in Combination With G-CSF to Mobilize and Collect ≥5 x 10^6 CD34+ Cells/kg in ≤4 Days and to Evaluate the Difference in Total Systemic Exposure in Patients With Non-Hodgkin's Lymphoma Weighing ≤70 kgPHASE4

COMPLETED · via plerixafor · NCT01164475

A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study of Mavorixafor in Patients With WHIM Syndrome With Open-Label ExtensionPHASE3

COMPLETED · via mavorixafor · NCT03995108

A Phase III Double-Blind Randomized Crossover Study of Plerixafor Versus G-CSF in the Treatment of Patients With WHIM Syndrome.PHASE2/PHASE3

COMPLETED · via plerixafor · NCT02231879

A Phase 3 Multicenter, Randomized, Double-Blind, Placebo-Controlled, Comparative Trial of Plerixafor (0.24 mg/kg) Plus G CSF (10 µg/kg) Versus G CSF (10 µg/kg) Plus Placebo to Mobilize and Collect ≥5 × 106 CD34+ Cells/kg in Non-Hodgkin's Lymphoma (NHL) Patients for Autologous TransplantationPHASE3

COMPLETED · via plerixafor · NCT01767714

Comparison of Plerixafor and G-CSF Versus G-CSF Alone for Stem Cell Mobilization in Patients With Multiple Myeloma Previously Treated With LenalidomidePHASE3

TERMINATED · via plerixafor · NCT01301963

A Prospective Randomized Trial Comparing Three Different Peripheral Stem Cell Mobilization Regimens in Patients With Symptomatic Multiple Myeloma or LymphomaPHASE3

COMPLETED · via plerixafor · NCT01146834

A Single Arm Study of Using Plerixafor Plus Donor Lymphocyte Infusion in the Treatment of Patients With Relapsed Acute Leukemia After Allogeneic Hematopoietic Stem Cell TransplantationPHASE2

UNKNOWN · via plerixafor · NCT06141304

ClinicalTrials.gov via the drug-target graph.

What's happening now

Recent therapeutic activity around this target — regulatory actions, clinical trials and safety signals for 2 drugs that target this protein, plus publications where such a drug is a genuine subject. Every item is reached indirectly through the drug, not the protein itself; incidental mentions (a paper that merely measures a drug) and press items are excluded.

Trial status changed2026-07-15
An Open-label, Non-randomized Study to Evaluate the Pharmacokinetics (PK), Safety and Tolerability of a Single Dose of Mavorixafor in Participants With Hepatic Impairment (HI) Compared to Matched Healthy Volunteers With Normal Hepatic Function
Status changed to Completed · ClinicalTrials.gov · via mavorixafor
Regulatory approval2026-04-27
Approval: Xolremdi (EMA)
ema · regulatory · ema · via mavorixafor
New publication2023-10-02
A phase III randomized crossover trial of plerixafor versus G-CSF for treatment of WHIM syndrome.
The Journal of clinical investigation · 2023 · 35 citations · Europe PMC · via plerixafor
Regulatory approval2022-12-16
Approval: Plerixafor Accord (EMA)
ema · regulatory · ema · via plerixafor
Regulatory approval2009-07-30
Approval: Mozobil (EMA)
ema · regulatory · ema · via plerixafor

Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.