LY2510924 / Eli Lilly 
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 2 Diseases   0 Trials   0 Trials   65 News 
  • ||||||||||  ulocuplumab (BMS-936564) / BMS
    Combined CXCR-4 Inhibition with Novel Agent GPC-100 (burixafor) and Beta 2 Adrenergic Receptor Blockade Enhances Cytarabine Response for Acute Myeloid Leukemia Blasts on Stroma (Halls G-H (San Diego Convention Center)) -  Nov 6, 2024 - Abstract #ASH2024ASH_5275;    
    P1
    Clinical trials of CXCR4 inhibitors have been conducted to mobilize AML out of the protected BM niche, including plerixafor with 7+3 or MEC, BL-8040 with cytarabine (araC), LY2510924 with idarubicin/araC, and ulocuplumab (human IgG4 antibody) with MEC...In addition, high throughput drug screening of AML on stroma, but not in suspension or on CXCL12 coated plates, revealed that combination of the CXCR4 inhibitor GPC-100 and beta blocker propranolol, with araC, increased drug sensitivity (reduced IC50 by ?4 to >10 fold) as compared to araC alone for AML cells on HS-5 human stromal cell line or autologous patient mesenchymal stromal cells...Conclusions : These studies support further investigation of whether simultaneous blockade of CXCR4 and ADRB2 may potentiate chemotherapy response in AML, perhaps by disrupting microenvironment mediated chemotherapy protection. Patients with new diagnosis AML may be more susceptible to this approach than R/R AML due to higher CXCR4 expression by both blasts and LSCs.
  • ||||||||||  LY2510924 / Eli Lilly
    Journal, Metastases:  Modeling the SDF-1/CXCR4 protein using advanced artificial intelligence and antagonist screening for Japanese anchovy. (Pubmed Central) -  Feb 19, 2024   
    We earlier found that this signaling is largely conserved in the Japanese anchovy (Engraulis japonicus, EJ), and a mere treatment of CXCR4 antagonist, AMD3100, leads to germ cell depletion and thereafter gonad sterilization...Three potential candidates, AMD3465, WZ811, and LY2510924, were selected and in vivo validation was conducted using Japanese anchovy embryos...The other three antagonists showed various degrees of PGC dispersion, but no significant effect compared to their solvent control at tested concentrations was observed. Cumulatively, our results suggests that AMD3645 might be a better candidate for abnormal PGC migration in Japanese anchovy and warrants further investigation.
  • ||||||||||  LY2510924 / Eli Lilly, mavorixafor (X4P-001) / X4 Pharma
    Biomarker, Journal:  Biological and mutational analyses of CXCR4-antagonist interactions and design of new antagonistic analogs. (Pubmed Central) -  Dec 26, 2023   
    The newly designed analogs displayed significantly increased binding to CXCR4, which supports the notion that negatively charged residues of CXCR4 can engage in interactions with moieties of positive charge of the antagonistic ligands. The results from these mutational, modeling and new analog design studies shed new insight into the molecular mechanisms of different types of antagonists in recognizing CXCR4 and guide the development of new therapeutic agents.
  • ||||||||||  LY2510924 / Eli Lilly
    Journal:  New Insights into the Determinants of Specificity in Human Type I Arginase: Generation of a Mutant That Is Only Active with Agmatine as Substrate. (Pubmed Central) -  Jul 2, 2022   
    Now, the specificity of arginase is completely altered, generating a chimeric species that is only active with agmatine as a substrate, by substituting I129T, N130Y, and T131A together with the elimination of residues P132, L133, and T134...Evidence was also obtained to define the loop B as a structural determinant for substrate affinity. Concretely, the double mutation D181T and V182E generate an enzyme with an essentially unaltered k value, but with a significantly increased K value for arginine and a significant decrease in affinity for its product ornithine.
  • ||||||||||  Review, Journal:  The contributory roles of the CXCL12/CXCR4/CXCR7 axis in normal and malignant hematopoiesis: A possible therapeutic target in hematologic malignancies. (Pubmed Central) -  Apr 8, 2022   
    Plerixafor, BKT140, LY2510924, PF-06747143, ulocuplumab, and NOX-A12 are among the most well-known CXCR4 and CXCL12 modulators that their therapeutic efficacies have been evaluated in different pre-clinical and clinical studies of hematologic malignancies. To have an overview of the importance of CXCL12/CXCR4 and CXCL12/CXCR7 axes in the pathogenesis of leukemia and to gather information about the latest advances as well as challenges in targeting these axes in clinical settings, the present review has begun with a discussion about how aberrant expression of CXCL12/CXCR4 and CXCL12/CXCR7 pathways might regulate leukemogenesis and ended by outlining the key news of preclinical and clinical investigations in leukemia treatment.
  • ||||||||||  LY2510924 / Eli Lilly
    Preclinical, Journal:  Preclinical Evaluation of [Cu]NOTA-CP01 as a PET Imaging Agent for Metastatic Esophageal Squamous Cell Carcinoma. (Pubmed Central) -  Jan 28, 2022   
    We developed a copper-64 (t = 12.7 h, 19% beta) labeling route of NOTA-CP01 derived from LY2510924, a cyclopeptide-based CXCR4 potent antagonist, in an attempt to noninvasively visualize CXCR4 expression in metastatic ESCC...The immunofluorescence and immunohistochemistry confirmed the positive expression of CXCR4 in the EC109 tumor and ESCC and metastatic lymph nodes of patients, respectively. We concluded that [Cu]NOTA-CP01 possessed a very high target engagement for CXCR4-positive ESCC and could be a potential candidate in the clinical detection of metastatic ESCC.
  • ||||||||||  LY2510924 / Eli Lilly
    Journal:  High-Contrast CXCR4-Targeted F-PET Imaging Using a Potent and Selective Antagonist. (Pubmed Central) -  Oct 7, 2021   
    We, therefore, aimed to develop a high-contrast CXCR4-targeting radiotracer by incorporating a hydrophilic linker and trifluoroborate radioprosthesis to LY2510924, a known CXCR4 antagonist...Based on high tumor-to-organ ratios, [F]BL08 may prove a valuable new tool for CXCR4-targeted PET imaging with potential for translation. The use of a PepBF moiety is a new approach for the orthogonal conjugation of organotrifluoroborates for F-labeling of peptides.
  • ||||||||||  Review, Journal:  Relevance of the CXCR4/CXCR7-CXCL12 axis and its effect in pathophysiological conditions. (Pubmed Central) -  Sep 3, 2021   
    It is therefore of great interest to investigate CXCR4/CXCR7/CXCL12 modulators in clinical development, with several CXCR4 and CXCL12 modulators such as plerixafor, ulocuplumab, balixafortide, and olaptesed pegol having already reached this stage...Contrary to CXCR4 and CXCL12 modulators, CXCR7 modulators have, thus far, not been extensively studied. Therefore, more (pre)clinical investigations are needed.
  • ||||||||||  LY2510924 / Eli Lilly, Tafinlar (dabrafenib) / Novartis
    Journal, Checkpoint inhibition, PD(L)-1 Biomarker, IO biomarker:  Manipulating immune system using nanoparticles for an effective cancer treatment: Combination of targeted therapy and checkpoint blockage miRNA. (Pubmed Central) -  Jul 9, 2021   
    The cationic PCL-PEI core containing Dab- and miR-200c- were coated with poly-L-glutamic acid conjugated with LY2510924, a CXCR-4 antagonist peptide, (PGA-pep) to obtain miR@PCL-PEI/Dab@PGA-pep nanoformulation...More importantly, effector T cells were increasingly infiltrated into the tumor, whereas the immunosuppressive factors like PD-L1 expression and regulatory T cells were significantly reduced. They, all together, promote the immune responses against the tumor, indicating the therapeutic efficiency of the current strategy in cancer treatment.
  • ||||||||||  Clinical, Review, Journal:  At the bedside: Profiling and treating patients with CXCR4-expressing cancers. (Pubmed Central) -  May 6, 2021   
    To date, Sanofi Genzyme's plerixafor is the only marketed CXCR4 inhibitor (i.e., Food and Drug Administration-approved in 2008 for stem cell mobilization)...These small molecules, peptides, and Abs include balixafortide (POL6326, Polyphor), mavorixafor (X4P-001, X4 Pharmaceuticals), motixafortide (BL-8040, BioLineRx), LY2510924 (Eli Lilly), and ulocuplumab (Bristol-Myers Squibb)...Biol. xx: xx-xx; 2020.
  • ||||||||||  LY2510924 / Eli Lilly, Vanflyta (quizartinib) / Daiichi Sankyo
    Clinical, Journal:  CXCR4 Inhibition Enhances Efficacy of FLT3 Inhibitors in FLT3-Mutated AML Augmented by Suppressed TGF-b Signaling. (Pubmed Central) -  Jul 8, 2020   
    In co-culture experiments of FLT3-ITD-AML and stromal cells, both silencing of TGF-b in stromal cells or TGF-b-receptor kinase inhibitor enhanced apoptosis by combined treatment. Disruption of the CXCL12/CXCR4 axis in FLT3-ITD-AML by LY2510924 and its negligible effects on normal immunocytes could safely enhance the potency of quizartinib, which may be further improved by blockade of TGF-b signaling.
  • ||||||||||  LY2510924 / Eli Lilly
    Journal:  [68Ga]Ga/[177Lu]Lu-BL01, a Novel Theranostic Pair for Targeting C-X-C Chemokine Receptor 4. (Pubmed Central) -  Jun 4, 2020   
    Disruption of the CXCL12/CXCR4 axis in FLT3-ITD-AML by LY2510924 and its negligible effects on normal immunocytes could safely enhance the potency of quizartinib, which may be further improved by blockade of TGF-b signaling. [68Ga]Ga-BL01 and [177Lu]Lu-BL01 are a promising theranostic pair for imaging and endoradiotherapy of CXCR4-expressing malignancies.
  • ||||||||||  LY2510924 / Eli Lilly
    Journal:  CDK12 and PAK2 as novel therapeutic targets for human gastric cancer. (Pubmed Central) -  Jun 3, 2020   
    We further identified FDA approved clinical drug procaterol can serve as an effective CDK12 inhibitor, leading to dramatic restriction of cancer cell proliferation and tumor growth in human gastric cancer cells and PDXs. Our data highlight the potential of CDK12/PAK2 as therapeutic targets for patients with gastric cancer, and we propose procaterol treatment as a novel therapeutic strategy for human gastric cancer.
  • ||||||||||  LY2510924 / Eli Lilly
    Journal:  β2AR-HIF-1α-CXCL12 signaling of osteoblasts activated by isoproterenol promotes migration and invasion of prostate cancer cells. (Pubmed Central) -  Apr 10, 2020   
    Our data highlight the potential of CDK12/PAK2 as therapeutic targets for patients with gastric cancer, and we propose procaterol treatment as a novel therapeutic strategy for human gastric cancer. These findings demonstrated that β2AR-HIF-1α-CXCL12 signaling in osteoblasts facilitates migration and invasion as well as EMT of prostate cancer cells, and may play a potential role in affecting bone metastasis of prostate cancer.
  • ||||||||||  LY2510924 / Eli Lilly
    Trial completion, Trial completion date, Trial primary completion date:  LY2510924, Idarubicin and Cytarabine in Patients With Relapsed or Refractory Acute Myeloid Leukemia (clinicaltrials.gov) -  Nov 15, 2019   
    P1b,  N=36, Completed, 
    Myeloid zinc finger-1 phosphorylation in mesenchymal stem cells drives the osteopontin-mediated cancer-associated fibroblast phenotype, which then increases the cancer cell stemness profile. Active, not recruiting --> Completed | Trial completion date: May 2022 --> Jul 2019 | Trial primary completion date: May 2021 --> Jul 2019
  • ||||||||||  LY2510924 / Eli Lilly
    Trial termination, Combination therapy, Metastases:  A Study of LY2510924 and Durvalumab in Participants With Solid Tumors (clinicaltrials.gov) -  Nov 17, 2017   
    P1a/1b,  N=45, Terminated, 
    Trial completion date: May 2021 --> May 2022 Active, not recruiting --> Terminated
  • ||||||||||  LY2510924 / Eli Lilly
    Trial primary completion date, Combination therapy, Metastases:  A Study of LY2510924 and Durvalumab in Participants With Solid Tumors (clinicaltrials.gov) -  Aug 22, 2017   
    P1a/1b,  N=45, Active, not recruiting, 
    LY2510924 did not improve efficacy but had an acceptable toxicity profile when added to SOC for ED-SCLC. Trial primary completion date: Mar 2018 --> Nov 2017
  • ||||||||||  LY2510924 / Eli Lilly
    Enrollment closed, Combination therapy, Metastases:  A Study of LY2510924 and Durvalumab in Participants With Solid Tumors (clinicaltrials.gov) -  Jul 28, 2017   
    P1a/1b,  N=45, Active, not recruiting, 
    Trial primary completion date: Mar 2018 --> Nov 2017 Recruiting --> Active, not recruiting
  • ||||||||||  LY2510924 / Eli Lilly
    Trial initiation date, Combination therapy, Metastases:  A Study of LY2510924 and Durvalumab in Participants With Solid Tumors (clinicaltrials.gov) -  Jul 5, 2016   
    P1a/1b,  N=45, Not yet recruiting, 
    Not yet recruiting --> Recruiting Initiation date: Jun 2016 --> Sep 2016
  • ||||||||||  LY2510924 / Eli Lilly
    Phase classification, Combination therapy, Metastases:  A Study of LY2510924 and Durvalumab in Participants With Solid Tumors (clinicaltrials.gov) -  Jun 1, 2016   
    P1a/1b,  N=45, Not yet recruiting, 
    Phase classification: P1 --> P1b Phase classification: P1 --> P1a/1b