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
References:
  1. FDA Approved Drug Products: Aphexda (motixafortide) for subcutaneous injection [Link]
Download FASTA Format
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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Associated Therapies
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.

TargetActionsOrganism
AC-X-C chemokine receptor type 4
inhibitor
Humans
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

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Product Ingredients
IngredientUNIICASInChI Key
Motixafortide acetate3ZPX60DV8A2639893-42-6GMUZYOKQKWMETH-AQDOTSTFSA-N
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
AphexdaInjection, powder, lyophilized, for solution62 mg/1.7mLSubcutaneousBioconnection B.V.2023-09-08Not applicableUS flag
AphexdaInjection, powder, lyophilized, for solution62 mg/1.7mLSubcutaneousBioLineRx USA Inc2023-09-08Not applicableUS flag

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
  1. 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]
  2. 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]
  3. FDA Approved Drug Products: Aphexda (motixafortide) for subcutaneous injection [Link]
  4. National Cancer Institute: Motixafortide May Improve Stem Cell Transplants for People with Multiple Myeloma [Link]
  5. FiercePharma: BioLineRx's Aphexda scores FDA nod to help myeloma patients undergo stem cell transplants [Link]
ChemSpider
64854351
RxNav
2664896
ChEBI
145536
Wikipedia
Motixafortide

Clinical Trials

Clinical Trials

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Injection, powder, lyophilized, for solutionSubcutaneous62 mg/1.7mL
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available

Targets

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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
  1. FDA Approved Drug Products: Aphexda (motixafortide) for subcutaneous injection [Link]

Drug created at May 20, 2019 14:36 / Updated at March 18, 2024 19:41