Motixafortide
Identification
- Summary
Motixafortide is a peptide inhibitor of CXCR4 used to mobilize hematopoietic stem cells prior to collection and autologous transplantation in multiple myeloma patients.
- Brand Names
- Aphexda
- Generic Name
- Motixafortide
- DrugBank Accession Number
- DB14939
- Background
Motixafortide is a cyclic peptide hematopoietic stem cell mobilizer used to improve stem cell collection prior to autologous transplantation.3 Hematopoietic stem cell transplantation (HSCT) is commonly employed in the context of hematologic cancers - high-dose chemotherapy regimens destroy cancerous blood cells, which are then replaced via infusion of the patient's own stem cells (i.e. an autologous transplant).4 Similar in mechanism to the previously approved plerixafor, motixafortide is an inhibitor of C-X-C Motif Chemokine Receptor 4 (CXCR4), a protein that helps to anchor stem cells to bone marrow matrix.3 When administered alongside filgrastim, another agent used to aid in stem cell collection, motixafortide enabled the collection of an adequate number of stem cells in ~92% of patients within two apheresis procedures, compared to ~26% of patients receiving only filgrastim.1
Motixafortide was approved by the FDA in September 2023, in combination with filgrastim, for use in stem cell mobilization prior to autologous stem cell transplant in patients with multiple myeloma.5 It has also been investigated alongside pembrolizumab for the treatment of pancreatic cancer.2
- Type
- Biotech
- Groups
- Approved, Investigational
- Biologic Classification
- Protein Based Therapies
Peptides - Protein Chemical Formula
- C97H144FN33O19S2
- Protein Average Weight
- 2159.6 Da
- Sequences
>Motixafortide sequence RRXCYXKKPYRXCR
Download FASTA FormatReferences:
- FDA Approved Drug Products: Aphexda (motixafortide) for subcutaneous injection [Link]
- Synonyms
- Motixafortide
- External IDs
- 4F-benzoyl-TN-14003
- BKT-140
- BKT140
- BL-8040
Pharmacology
- Indication
Motixafortide is indicated for use in combination with filgrastim to mobilize hematopoietic stem cells to the peripheral blood for collection and subsequent autologous transplantation in patients with multiple myeloma.3
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- Contraindications & Blackbox Warnings
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- Pharmacodynamics
In vitro studies have shown motixafortide to have an IC50 towards CXCR4 of 0.42 – 4.5 nM, with a binding affinity and dissociation rate that allows receptor occupancy to be maintained >72 hours.3 In healthy volunteers administered motixafortide monotherapy, CD34+ cell counts increased over time and reached maximal levels at 16 hours postdose.3 In the GENESIS study, motixafortide in combination with filgrastim mobilized significantly greater CD34+ HSPC numbers within two apheresis procedures compared to filgrastim with placebo, while preferentially mobilizing increased numbers of immunophenotypically and transcriptionally primitive HSPCs.1
- Mechanism of action
Motixafortide is an inhibitor of C-X-C Motif Chemokine Receptor 4 (CXCR4) that blocks the binding of its ligand, stromal-derived factor-1α (SDF-1α)/C-X-C Motif Chemokine Ligand 12 (CXCL12).3 Both CXCR4 and SDF-1α play a role in the trafficking of hematopoietic stem cells to the bone marrow compartment, with CXCR4 helping to anchor stem cells to the marrow matrix (via SDF-1α or the induction of other adhesion molecules).3 The inhibition of CXCR4 thus results in elevations in circulating hematopoietic stem and progenitor cells into the peripheral circulation, facilitating their collection for the purposes of autologous transplantation.
Target Actions Organism AC-X-C chemokine receptor type 4 inhibitorHumans - Absorption
Following subcutaneous injection, motixafortide Tmax ranged from 0.25 to 1.17 hours.3
- Volume of distribution
In a typical patient, the estimated volume of distribution to the central compartment is 27 liters.3
- Protein binding
Motixafortide is extensively (>99%) bound to human plasma proteins,3 although the specific protein(s) to which it may bind are unclear.
- Metabolism
Motixafortide is broken down via non-specific catabolic processes to smaller peptides and amino acids.3
- Route of elimination
In animal studies in which radiolabeled motixafortide was administered, approximately 80% of the radioactive material was excreted in the urine. No parent drug was detected in the urine, and no single metabolite exceeded 30% of the total clearance.3
- Half-life
The effective half-life of motixafortide in human plasma is approximately 2 hours.3
- Clearance
In a typical patient, the apparent total clearance of motixafortide is 46.5 L/h.3
- Adverse Effects
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- Toxicity
There are no data regarding overdosage with motixafortide.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.Not Available
- Food Interactions
- No interactions found.
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- Product Ingredients
Ingredient UNII CAS InChI Key Motixafortide acetate 3ZPX60DV8A 2639893-42-6 GMUZYOKQKWMETH-AQDOTSTFSA-N - Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Aphexda Injection, powder, lyophilized, for solution 62 mg/1.7mL Subcutaneous Bioconnection B.V. 2023-09-08 Not applicable US Aphexda Injection, powder, lyophilized, for solution 62 mg/1.7mL Subcutaneous BioLineRx USA Inc 2023-09-08 Not applicable US
Categories
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- Not Available
- Kingdom
- Organic Compounds
- Super Class
- Organic Acids
- Class
- Carboxylic Acids and Derivatives
- Sub Class
- Amino Acids, Peptides, and Analogues
- Direct Parent
- Peptides
- Alternative Parents
- Not Available
- Substituents
- Not Available
- Molecular Framework
- Not Available
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- DA9G065962
- CAS number
- 664334-36-5
References
- General References
- Crees ZD, Rettig MP, Jayasinghe RG, Stockerl-Goldstein K, Larson SM, Arpad I, Milone GA, Martino M, Stiff P, Sborov D, Pereira D, Micallef I, Moreno-Jimenez G, Mikala G, Coronel MLP, Holtick U, Hiemenz J, Qazilbash MH, Hardy N, Latif T, Garcia-Cadenas I, Vainstein-Haras A, Sorani E, Gliko-Kabir I, Goldstein I, Ickowicz D, Shemesh-Darvish L, Kadosh S, Gao F, Schroeder MA, Vij R, DiPersio JF: Motixafortide and G-CSF to mobilize hematopoietic stem cells for autologous transplantation in multiple myeloma: a randomized phase 3 trial. Nat Med. 2023 Apr;29(4):869-879. doi: 10.1038/s41591-023-02273-z. Epub 2023 Apr 17. [Article]
- Bockorny B, Semenisty V, Macarulla T, Borazanci E, Wolpin BM, Stemmer SM, Golan T, Geva R, Borad MJ, Pedersen KS, Park JO, Ramirez RA, Abad DG, Feliu J, Munoz A, Ponz-Sarvise M, Peled A, Lustig TM, Bohana-Kashtan O, Shaw SM, Sorani E, Chaney M, Kadosh S, Vainstein Haras A, Von Hoff DD, Hidalgo M: BL-8040, a CXCR4 antagonist, in combination with pembrolizumab and chemotherapy for pancreatic cancer: the COMBAT trial. Nat Med. 2020 Jun;26(6):878-885. doi: 10.1038/s41591-020-0880-x. Epub 2020 May 25. [Article]
- FDA Approved Drug Products: Aphexda (motixafortide) for subcutaneous injection [Link]
- National Cancer Institute: Motixafortide May Improve Stem Cell Transplants for People with Multiple Myeloma [Link]
- FiercePharma: BioLineRx's Aphexda scores FDA nod to help myeloma patients undergo stem cell transplants [Link]
- External Links
- ChemSpider
- 64854351
- 2664896
- ChEBI
- 145536
- Wikipedia
- Motixafortide
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 3 Active Not Recruiting Treatment Multiple Myeloma (MM) 1 2 Completed Treatment Acute Lymphoblastic Leukemia (ALL) / Acute Myeloid Leukemia / Chronic Myelogenous Leukemia (CML) / Hodgkins Disease (HD) / Multiple Myeloma (MM) / Myelodysplastic Syndrome / Myeloproliferative Neoplasms (MPNs) / Non-Hodgkin's Lymphoma (NHL) 1 2 Completed Treatment Acute Myeloid Leukemia 1 2 Completed Treatment Aplastic Anemia / Hypo-Plastic Myelodysplastic Syndrome (MDS) 1 2 Completed Treatment Pancreatic Adenocarcinoma Metastatic 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection, powder, lyophilized, for solution Subcutaneous 62 mg/1.7mL - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
- Not Available
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Virus receptor activity
- Specific Function
- 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. Acts as a receptor for extracellular ubiq...
- Gene Name
- CXCR4
- Uniprot ID
- P61073
- Uniprot Name
- C-X-C chemokine receptor type 4
- Molecular Weight
- 39745.055 Da
References
- FDA Approved Drug Products: Aphexda (motixafortide) for subcutaneous injection [Link]
Drug created at May 20, 2019 14:36 / Updated at May 20, 2024 12:05