Motixafortide: First Approval

Hoy, Sheridan M.

doi:10.1007/s40265-023-01962-w

Cited by 18 publications

(7 citation statements)

References 20 publications

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“…Motixafortide is a 14-mer cyclic peptide amide that acts as a selective chemokine receptor 4 (CXCR4) inhibitor. It comprises a disulfide bridge between Cys 4 and Cys 13 (blue) ( Figure 7 ) [ 34 ]. Motixafortide is used with filgrastim (G-CSF) to mobilize hematopoietic stem cells (HSCs) in patients with multiple myeloma [ 35 ].…”

Section: Peptidesmentioning

confidence: 99%

“…Motixafortide is used with filgrastim (G-CSF) to mobilize hematopoietic stem cells (HSCs) in patients with multiple myeloma [ 35 ]. However, the FDA previously approved two small molecules (maraviroc and plerixafor) and one monoclonal antibody (mogamulizumab); motixafortide is the first peptide-based drug to be approved as a chemokine antagonist [ 36 ] and was granted an orphan drug designation [ 34 ]. It’s noteworthy that a cyclic peptide, balixafortide, functions similarly to motixafortide, but it fell short of meeting the co-primary endpoint related to the objective response rate (ORR) [ 36 ].…”

Section: Peptidesmentioning

confidence: 99%

“…Clinical studies are ongoing for the mobilization of CD34+ HSCs for gene therapy in patients with sickle cell disease [ 34 , 36 ]. In phase I, motixafortide was able to rapidly mobilize CD34+ cells and immune cells in healthy volunteers [ 37 , 38 , 39 ].…”

Section: Peptidesmentioning

confidence: 99%

“…Biokine Therapeutics acquired motixafortide from Kyoto University, and then the former entered into an exclusive worldwide license agreement with BioLineRx for its development and commercialization. It was approved by the FDA (in combination with filgrastim) on 08 September 2023 [ 34 ].…”

Section: Peptidesmentioning

confidence: 99%

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2023 FDA TIDES (Peptides and Oligonucleotides) Harvest

Al Shaer,

Al Musaimi,

Albericio

et al. 2024

Pharmaceuticals

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A total of nine TIDES (pepTIDES and oligonucleoTIDES) were approved by the FDA during 2023. The four approved oligonucleotides are indicated for various types of disorders, including amyotrophic lateral sclerosis, geographic atrophy, primary hyperoxaluria type 1, and polyneuropathy of hereditary transthyretin-mediated amyloidosis. All oligonucleotides show chemically modified structures to enhance their stability and therapeutic effectiveness as antisense or aptamer oligomers. Some of them demonstrate various types of conjugation to driving ligands. The approved peptides comprise various structures, including linear, cyclic, and lipopeptides, and have diverse applications. Interestingly, the FDA has granted its first orphan drug designation for a peptide-based drug as a highly selective chemokine antagonist. Furthermore, Rett syndrome has found its first-ever core symptoms treatment, which is also peptide-based. Here, we analyze the TIDES approved in 2023 on the basis of their chemical structure, medical target, mode of action, administration route, and common adverse effects.

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Section: Peptidesmentioning

confidence: 99%

Section: Peptidesmentioning

confidence: 99%

Section: Peptidesmentioning

confidence: 99%

Section: Peptidesmentioning

confidence: 99%

See 2 more Smart Citations

2023 FDA TIDES (Peptides and Oligonucleotides) Harvest

Al Shaer,

Al Musaimi,

Albericio

et al. 2024

Pharmaceuticals

View full text Add to dashboard Cite

show abstract

“…Motixafortide is a selective CXCR4 inhibitor that acts as a hematopoietic stem cell mobilizer (Crees et al 2023a ). Motixafortide was approved for use in combination with filgrastim to mobilize hematopoietic stem cells to the peripheral blood in patients with multiple myeloma (Hoy 2023d ). Motixafortide was found to be well tolerated, with the most frequent AE being transient injection-site reactions (pain, erythema, and pruritis) and systemic reactions (flushing, pruritis, urticaria, and erythema) (Crees et al 2023b ).…”

Section: Hematologymentioning

confidence: 99%

A year in pharmacology: new drugs approved by the US Food and Drug Administration in 2023

Kayki-Mutlu,

Aksoyalp,

Wojnowski

et al. 2024

Naunyn-Schmiedeberg's Arch Pharmacol

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With 54 new drugs and seven cellular and gene therapy products, the approvals by the US Food and Drug Administration (FDA) recovered 2023 from the 2022 dent back to the levels of 2020–2021. As in previous years of this annual review, we assign these new drugs to one of three levels of innovation: first drug against a condition (“first-in-indication”), first drug using a novel molecular mechanism (“first-in-class”), and “next-in-class,” i.e., a drug using an already exploited molecular mechanism. We identify four (7%) “first-in-indication,” 22 (36%) “first-in-class,” and 35 (57%) “next-in-class” drugs. By treatment area, rare diseases (54%) and cancer drugs (23%) were once again the most prevalent (and partly overlapping) therapeutic areas. Other continuing trends were the use of accelerated regulatory approval pathways and the reliance on biopharmaceuticals (biologics). 2023 marks the approval of a first therapy based on CRISPR/Cas9 gene editing.

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CXCR4 up‐regulation mediated by USP1 deubiquitination promotes the tumorigenesis and immune escape in esophageal squamous‐cell carcinoma

Xiao,

Xu,

et al. 2024

J Biochem & Molecular Tox

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CXC chemokine receptor 4 (CXCR4) and ubiquitin specific protease 1 (USP1) have been reported to involve in the tumorigenesis of esophageal squamous‐cell carcinoma (ESCC). Here, we investigated whether USP1 induced CXCR4 deubiquitination in regulating ESCC progression. MTT assay, 5‐ethynyl‐2'‐deoxyuridine assay, flow cytometry, transwell assay and ELISA analysis were used to detect cell oncogenic phenotypes, macrophage phenotypes, inflammatory cytokines production, the cytotoxicity of cytokine‐induced killer (CIK) cells and CD8 + T cell apoptosis. Protein interaction was determined by immunoprecipitation assay. Cellular ubiquitination detected the ubiquitination effect on CXCR4. A mouse xenograft model was established for in vivo experiments. CXCR4 was highly expressed in ESCC tissues and cells. Functionally, CXCR4 silencing suppressed ESCC cell proliferation, invasion, and induced cell apoptosis. Moreover, CXCR4 deficiency suppressed cancer cell immune escape by suppressing macrophage M2 polarization, elevating inflammatory cytokines produced by PBMCs, enhancing the cytotoxicity of CIK cells, and suppressing CD8 + T cell apoptosis. A high USP1 expression was observed in ESCC, USP1 interacted with CXCR4 and enhanced its protein stability through deubiquitination. USP1 silencing suppressed ESCC cell proliferation, invasion, and immune escape, which were reversed by CXCR4 overexpression. In vivo assay showed that USP1 deficiency impeded tumor growth by regulating CXCR4. Besides, fused in sarcoma (FUS) was confirmed to bind to USP1 and stabilized its mRNA expression, and could regulate CXCR4 via USP1. In conclusion, USP1 stabilized CXCR4 by removing ubiquitination on CXCR4, thereby promoting ESCC cell proliferation, invasion, and immune escape in vitro, and tumor growth in vivo.

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Motixafortide: First Approval

Cited by 18 publications

References 20 publications

2023 FDA TIDES (Peptides and Oligonucleotides) Harvest

2023 FDA TIDES (Peptides and Oligonucleotides) Harvest

A year in pharmacology: new drugs approved by the US Food and Drug Administration in 2023

CXCR4 up‐regulation mediated by USP1 deubiquitination promotes the tumorigenesis and immune escape in esophageal squamous‐cell carcinoma

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