ArticleBlood2007
MLN3897, a novel CCR1 inhibitor, impairs osteoclastogenesis and inhibits the interaction of multiple myeloma cells and osteoclasts.
Article in Blood, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 150 citations in OpenAlex.
- Spatial transcriptomic atlas of aggressive osteosarcomas reveals shared immune landscape and targetable surface markers.Nature communications · 2026Article
- Exhausted CD8⁺ T cells promote ovarian cancer immunosuppression via CCL3-Driven M2 macrophage polarization.Cell death & disease · 2026Article
- MAFB: a key regulator of myeloid commitment involved in hematological diseases.Cell death discovery · 2025Review
- Complement C3a promotes the formation of osteoclasts by inhibiting Sirt1 to activate the PI3K/PDK1/SGK3 pathway in patients with multiple myeloma.Journal of translational medicine · 2025Article
- Fluorophore-Labeled Pyrrolones Targeting the Intracellular Allosteric Binding Site of the Chemokine Receptor CCR1.ACS pharmacology & translational science · 2024Article
- Favorable impact of PD1/PD-L1 antagonists on bone remodeling: an exploratory prospective clinical study and ex vivo validation.Journal for immunotherapy of cancer · 2024Article
- Research progress of the chemokine/chemokine receptor axes in the oncobiology of multiple myeloma (MM).Cell communication and signaling : CCS · 2024Review
- CCL3 in the bone marrow microenvironment causes bone loss and bone marrow adiposity in aged mice.JCI insight · 2023Article
- Pathogenesis and Treatment of Myeloma-Related Bone Disease.International journal of molecular sciences · 2022Review
- Targeting Chemokine Receptor CCR1 as a Potential Therapeutic Approach for Multiple Myeloma.Frontiers in endocrinology · 2022Review
- Expression of the chemokine receptor CCR1 promotes the dissemination of multiple myeloma plasma cellsHaematologica · 2021Article
- Pathogenesis and treatment of multiple myeloma bone disease.The Japanese dental science review · 2021Review
- Review
- Modulation of the chemokine/chemokine receptor axis as a novel approach for glioma therapy.Pharmacology & therapeutics · 2021Review
- Chemokines orchestrate tumor cells and the microenvironment to achieve metastatic heterogeneity.Cancer metastasis reviews · 2021Review
- Management of Myeloma Bone Lesions.International journal of molecular sciences · 2021Review
- Tumour Dissemination in Multiple Myeloma Disease Progression and Relapse: A Potential Therapeutic Target in High-Risk Myeloma.Cancers · 2020Review
- Curcumin inhibits the migration of osteoclast precursors and osteoclastogenesis by repressing CCL3 production.BMC complementary medicine and therapies · 2020Article
- Selective Allosteric Modulation of N-Terminally Cleaved, but Not Full Length CCL3 in CCR1.ACS pharmacology & translational science · 2019Article
- Chemokines and Chemokine Receptors: New Targets for Cancer Immunotherapy.Frontiers in immunology · 2019Review
1 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
21 authors at 4 institutions in 2 countries.
Funding
Abstract
The interaction between osteoclasts (OCs) and multiple myeloma (MM) cells plays a key role in the pathogenesis of MM-related osteolytic bone disease (OBD). MM cells promote OC formation and, in turn, OCs enhance MM cell proliferation. Chemokines are mediators of MM effects on bone and vice versa; in particular, CCL3 enhances OC formation and promotes MM cell migration and survival. Here, we characterize the effects of MLN3897, a novel specific antagonist of the chemokine receptor CCR1, on both OC formation and OC-MM cell interactions. MLN3897 demonstrates significant impairment of OC formation (by 40%) and function (by 70%), associated with decreased precursor cell multinucleation and down-regulation of c-fos signaling. OCs secrete high levels of CCL3, which triggers MM cell migration; conversely, MLN3897 abrogates its effects by inhibiting Akt signaling. Moreover, MM cell-to-OC adhesion was abrogated by MLN3897, thereby inhibiting MM cell survival and proliferation. Our results therefore show novel biologic sequelae of CCL3 and its inhibition in both osteoclastogenesis and MM cell growth, providing the preclinical rationale for clinical trials of MLN3897 to treat OBD in MM.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.