Motixafortide

Specification

• Cat#: THP-1105
• Product Name: Motixafortide
• Description: Motixafortide is a peptide inhibitor of CXCR4 used to mobilize hematopoietic stem cells prior to collection and autologous transplantation in multiple myeloma patients.
• Sequences: >Motixafortide sequence RRXCYXKKPYRXCR
• Species: Human
• Molecular Weight: 2159.6 Da
• Introduction: Motixafortide is a cyclic peptide hematopoietic stem cell mobilizer used to improve stem cell collection prior to autologous transplantation. 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). 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. 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. 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. It has also been investigated alongside pembrolizumab for the treatment of pancreatic cancer.
• Cas No: 664334-36-5
• Formula: C97H144FN33O19S2
• Biologic Classification: Protein Based Therapies Peptides
• Physical Appearance: Solid

Pharmaceutical Information

• 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. In healthy volunteers administered motixafortide monotherapy, CD34+ cell counts increased over time and reached maximal levels at 16 hours postdose. 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.
• 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). 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). 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.
• Affected organisms: Humans and other mammals
• Targets: 1. C-X-C chemokine receptor type 4