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A peptide derived from horseshoe crab blood that, in one injection, empties stem cells out of the bone marrow for collection.
Also known as: BL-8040 · BKT140 · TF14016 · 4F-benzoyl-TN14003 · Aphexda
Part of the Foundational & therapeutic peptides cluster
Overview
Motixafortide (Aphexda, BL-8040) is a synthetic 14-amino-acid CXCR4 antagonist peptide derived from a horseshoe crab protein. By blocking the CXCR4 receptor that anchors haematopoietic stem cells in bone marrow, it mobilises them into the blood; the FDA approved it in September 2023 in combination with filgrastim for stem-cell collection before autologous transplantation in multiple myeloma. It is also being studied in pancreatic cancer, AML and sickle cell disease.
Source & context
Biological / chemical source: Synthetic 14-residue peptide modified from a horseshoe crab protein
Primary research or clinical context: Approved (US FDA, September 2023) with filgrastim for stem-cell mobilisation before autologous transplantation in multiple myeloma; investigational in pancreatic cancer, AML and sickle cell disease
What motixafortide is
Motixafortide is a 14-residue synthetic peptide that antagonises CXCR4, the chemokine receptor that retains haematopoietic stem cells in the bone marrow niche. Its origin is unusual: the sequence was modified from a naturally occurring protein of the horseshoe crab, an animal whose blood has long supplied the endotoxin-detecting reagent used in pharmaceutical quality control. Developed by Biokine Therapeutics and BioLineRx under the codes BKT140 and BL-8040, it was approved by the US FDA on 11 September 2023, under the brand name Aphexda, for use with filgrastim (G-CSF) to mobilise stem cells for collection before autologous transplantation in multiple myeloma (Hoy, Drugs 2023).
Sequence and chemistry
The IUPHAR one-letter record is RRXCYXKKPYRXCR, where X marks residues that are non-canonical; the two cysteines form a disulfide ring, and the PubChem synonym 4F-benzoyl-TN14003 records a 4-fluorobenzoyl group on the N-terminus. The molecular formula, C97H144FN33O19S2, includes that single fluorine. At about 2.2 kDa it is small for a receptor antagonist. In functional assays motixafortide behaves as an inverse agonist at CXCR4 — it does not merely block the receptor's natural ligand CXCL12 but suppresses its baseline signalling (IUPHAR record).
Mechanism: cutting the tether
Haematopoietic stem cells stay in the marrow because CXCR4 on their surface binds CXCL12 (SDF-1) secreted by marrow stromal cells. Stem-cell transplantation needs those cells in the peripheral blood, where they can be collected by apheresis. Filgrastim (G-CSF) mobilises them indirectly and slowly over several days; blocking CXCR4 directly releases them within hours. Motixafortide's long receptor occupancy allowed a single-injection protocol in the pivotal trial, and the same mechanism — releasing cells from a CXCL12-rich niche — is why it is being tested to sensitise leukaemia cells and to improve immune infiltration of solid tumours.
Clinical evidence
The pivotal GENESIS study was a randomised phase 3 trial of motixafortide plus G-CSF versus placebo plus G-CSF for stem-cell mobilisation before autologous transplantation in multiple myeloma (Crees et al., Nature Medicine 2023); on its basis the FDA approved the combination in September 2023. Earlier, the COMBAT trial evaluated BL-8040 with pembrolizumab and chemotherapy in metastatic pancreatic cancer, testing the hypothesis that CXCR4 blockade improves anti-tumour immune responses (Bockorny et al., Nature Medicine 2020). The 2026 ASCO guideline update on white-cell growth factors notes the approval of an additional CXCR4 inhibitor for use with colony-stimulating factors in mobilisation (Gyawali et al., Journal of Clinical Oncology 2026).
Ongoing trials as of September 2026
ClinicalTrials.gov lists ten studies, including a recruiting phase 3 mobilisation trial, phase 1 studies of motixafortide for stem-cell collection in sickle cell disease and for gene-editing programmes that need a patient's own cells, a phase 2 study in acute myeloid leukaemia aimed at sensitising minimal residual disease, and a phase 4 comparison of premedication regimens. CXCR4 remains an active target across haematological malignancies (Korbecki et al., Leukemia 2024).
Relation to other peptides on this site
Motixafortide is a receptor antagonist, the pharmacological opposite of most peptides in this directory. The closest structural relatives on the site are the cyclic, disulfide-stabilised hormone analogues — octreotide, lanreotide, ziconotide — which share its strategy of locking a short chain into a rigid ring. Its therapeutic neighbours are pegcetacoplan and zilucoplan, peptides that also act by blocking a protein rather than mimicking a hormone.
Sequence
One-letter sequence commonly cited for Motixafortide (educational; isoforms and modifications may differ):
RRXCYXKKPYRXCR
X = non-canonical residue in the IUPHAR one-letter record (the peptide carries a 4-fluorobenzoyl N-terminal group and modified residues). X marks a non-canonical residue — see the structure block below. (Plotted as alanine on the wheel.)
Residues plotted ~100° apart around an α-helix — clustering of one color reveals an amphipathic face.
Structure & chemistry
Molecular identity & reference confidence
Source-supported reference
Reference values are taken from the cited molecular record or curated profile. A database match is not independent laboratory verification; modifications, counter-ions, and formulations can change the measured mass.
- Molecular form
- 14-residue polypeptide modified from a naturally occurring horseshoe crab protein, with a Cys–Cys disulfide; N-terminally 4-fluorobenzoylated (synonym 4F-benzoyl-TN14003)
- Species
- Not established by this molecular identity audit
- Termini (N / C)
- Not specified / Not specified
Average reference mass
Reference policy updated: 2026-10-05
- IUPHAR/BPS source snapshot · 2026-10-01
- PubChem molecular record · 2026-10-01
- Molecular formula
- C97H144FN33O19S2
- Average reference mass
- ≈ 2,159.5
- Receptors
- CXCR4 (C-X-C motif chemokine receptor 4); acts as an inverse agonist in [35S]GTPγS binding assays (IUPHAR record)
- Backbone
- 14-residue polypeptide modified from a naturally occurring horseshoe crab protein, with a Cys–Cys disulfide; N-terminally 4-fluorobenzoylated (synonym 4F-benzoyl-TN14003)
- Status
- Approved: US FDA, 11 September 2023, with filgrastim for HSC mobilisation in multiple myeloma. Orphan drug designations held
- PubChem CID: 91865076
- IUPHAR ligand: 10679
- CAS RN: 664334-36-5
- UNII: DA9G065962
Chemistry values: curated profile, PubChem, IUPHAR/BPS Guide to Pharmacology · fetched 2026-10-01.
Clinical development snapshot
ClinicalTrials.gov lists 10 registered studies with “Motixafortide” as an intervention (snapshot 2026-10-01). A registry footprint is not evidence of efficacy or approval.
| NCT | Title | Phase | Status | Updated |
|---|---|---|---|---|
| NCT04543071 | Chemo4METPANC Combination Chemokine Inhibitor, Immunotherapy, and Chemotherapy in Pancreatic Adenocarcinoma | Phase 2 | active not recruiting | 2026-09-21 |
| NCT06514508 | Mobilization of Stem Cells With Motixafortide (BL-8040) in Combination With G-CSF in Multiple Myeloma Patients | Phase 3 | recruiting | 2026-09-14 |
| NCT06442761 | SCD Stem Cell Mobilization and Apheresis Using Motixafortide | Phase 1 | recruiting | 2026-09-08 |
| NCT07392970 | Motixafortide for MRD Sensitization in AML | Phase 2 | recruiting | 2026-07-24 |
| NCT07101445 | Evaluating Premedication Regimens (Methylprednisolone vs Dexamethasone-based) for the Prevention of Systemic a | Phase 4 | recruiting | 2026-07-23 |
| NCT06506461 | Gene Editing For Sickle Cell Disease | Phase 1 | recruiting | 2026-05-05 |
Motixafortide — reconstitution calculator
Enter how much peptide is in the vial and how much diluent (e.g. bacteriostatic water) is added. The tool returns the resulting solution concentration — and, for any amount you type, the volume it corresponds to. This is educational arithmetic, not a dosing recommendation.
Reference form: 14-residue polypeptide modified from a naturally occurring horseshoe crab protein, with a Cys–Cys disulfide; N-terminally 4-fluorobenzoylated (synonym 4F-benzoyl-TN14003)Average reference mass: 2,159.5 Da
Enter an amount to see the volume it corresponds to.
Educational concentration mathematics only. This tool does not recommend a dose, amount, or protocol, and nothing here is medical advice. Many peptides are not authorized by Health Canada for human use — see our reconstitution and bacteriostatic-water guides for context.
Change log
Dated observations from the data pipeline (registry flags, trial footprints, identifiers) and editorial reviews of this profile.
- IdentifiersCross-linked to IUPHAR ligand 10679 and PubChem CID 91865076.
- TrialsClinicalTrials.gov snapshot added: 10 registered studies, highest phase 4.
- EditorialProfile content reviewed and updated by the editorial team.
FAQ about Motixafortide
What is Motixafortide?+
Motixafortide (Aphexda, BL-8040) is a synthetic 14-amino-acid CXCR4 antagonist peptide derived from a horseshoe crab protein. By blocking the CXCR4 receptor that anchors haematopoietic stem cells in bone marrow, it mobilises them into the blood; the FDA approved it in September 2023 in combination with filgrastim for stem-cell collection before autologous transplantation in multiple myeloma. It is also being studied in pancreatic cancer, AML and sickle cell disease.
What Canadian product status is recorded for Motixafortide?+
Canadian product status for Motixafortide has not been verified in this profile. No verified record here does not mean no authorization exists. Status depends on the product, formulation and use; consult Health Canada's product records.
What is the typical length of Motixafortide?+
Motixafortide is commonly described as approximately 14 amino acids (CXCR4 antagonist peptide).
What is motixafortide?+
A synthetic 14-amino-acid CXCR4 antagonist peptide (Aphexda, BL-8040) that mobilises stem cells from bone marrow into the blood. FDA-approved in September 2023 with filgrastim for stem-cell collection in multiple myeloma.
How does motixafortide work?+
It blocks CXCR4, the receptor that anchors stem cells to marrow stroma via CXCL12, releasing them into the circulation for apheresis. In assays it acts as an inverse agonist.
Where does motixafortide come from?+
Its sequence was modified from a naturally occurring horseshoe crab protein, then synthesised with a 4-fluorobenzoyl N-terminus and a disulfide ring.
Is motixafortide approved?+
Yes, by the US FDA on 11 September 2023 for use with filgrastim in multiple myeloma stem-cell mobilisation. It holds orphan designations and is investigational in other cancers.
Is motixafortide used in cancer treatment itself?+
It has been tested with pembrolizumab and chemotherapy in pancreatic cancer (COMBAT trial) and is in a phase 2 AML trial, but its approval is for stem-cell mobilisation only.
Related peptides
References & further reading
- 1.Hoy SM (2023). Motixafortide: First Approval. Drugs
- 2.Crees ZD et al. (2023). Motixafortide and G-CSF to mobilize hematopoietic stem cells for autologous transplantation in multiple myeloma: a randomized phase 3 trial. Nature Medicine
- 3.Bockorny B et al. (2020). BL-8040, a CXCR4 antagonist, in combination with pembrolizumab and chemotherapy for pancreatic cancer: the COMBAT trial. Nature Medicine
- 4.Gyawali B et al. (2026). WBC Growth Factors: ASCO Guideline Update. Journal of Clinical Oncology
- 5.Korbecki J et al. (2024). CXCR4 as a therapeutic target in acute myeloid leukemia. Leukemia
- 6.PubChem — Motixafortide (CID 91865076)