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33 News |  |
- | LY2874455 / Eli Lilly
Journal: Selective autophagy of the immunoproteasomes suppresses innate inflammation. (Pubmed Central) - Aug 24, 2024
LY2874455 suppresses inflammation induced by lipopolysaccharide both in vivo and in vitro through autophagic degradation of the immunoproteasomes. In summary, our work uncovers a mechanism of inflammation suppression by autophagy in macrophages.
- | LY2874455 / Eli Lilly
Journal: Design, synthesis and antitumor activity of a novel FGFR2-selective degrader to overcome resistance of the FGFR2V564F gatekeeper mutation based on a pan-FGFR inhibitor. (Pubmed Central) - Jul 10, 2024
In this study, we designed several PROTACs with different E3 ligands based on LY2874455...In summary, we identified 28e as a novel selective degrader of FGFR2 with high potency and high potential to overcome resistance to gatekeeper mutation. The discovery of 28e provides new evidence for the strategy of pan-inhibitor-based development of selective degrading agents.
- | LY2874455 / Eli Lilly
Journal: Pharmacological induction of autophagy reduces inflammation in macrophages by degrading immunoproteasome subunits. (Pubmed Central) - Mar 10, 2024
In mice, LY2874455 protected against LPS-induced acute lung injury and dextran sulfate sodium (DSS)-induced colitis and caused low levels of proinflammatory cytokines and immunoproteasomes. These findings suggested that selective autophagy of the immunoproteasome was a key regulator of signaling via the innate immune system.
- The FGFR axis is a potential radiosensitization target. (LEVEL 2, EXHIBIT HALL D) - Sep 16, 2023 - Abstract #AACRNCIEORTC2023AACR_NCI_EORTC_311;
- | merestinib (LY2801653) / Eli Lilly, LY2874455 / Eli Lilly
Preclinical, Journal: Targeting MET and FGFR in Relapsed or Refractory Acute Myeloid Leukemia: Preclinical and Clinical Findings, and Signal Transduction Correlates. (Pubmed Central) - Mar 2, 2023
These findings suggested that selective autophagy of the immunoproteasome was a key regulator of signaling via the innate immune system. We provide prospective, preliminary evidence that MET and FGFR are biologically active and safely targetable pathways in AML.
- | Journal: Strategies to inhibit FGFR4 V550L-driven rhabdomyosarcoma. (Pubmed Central) - Sep 14, 2022
We provide prospective, preliminary evidence that MET and FGFR are biologically active and safely targetable pathways in AML. Our results pave the way for precision medicine approaches against FGFR4 V550L-driven RMS.
- | LY2874455 / Eli Lilly, Verzenio (abemaciclib) / Eli Lilly
Journal: LY2874455 and Abemaciclib Reverse FGF3/4/19/CCND1 Amplification Mediated Gefitinib Resistance in NSCLC. (Pubmed Central) - Jul 13, 2022
Mechanistically, FGFs/CCND1 activated the MAPK pathway, which was abolished by the combination drugs. Our study provides a rationale for clinical testing of dual targeting FGFR and CCND1 with LY2874455 and abemaciclib in NSCLC patients who harbored FGF3/4/19/CCND1 amplification.
- | LY2874455 / Eli Lilly
Journal: Radiosensitization by the Selective Pan-FGFR Inhibitor LY2874455. (Pubmed Central) - Jun 19, 2022
This is the first report to show the radiosensitizing effect of a selective pan-FGFR inhibitor. These data suggest the potential efficacy of LY2874455 as a radiosensitizer, warranting clinical validation.
- | Iclusig (ponatinib) / Takeda, Otsuka, Incyte, lestaurtinib (CEP-701) / Teva, Kyowa Kirin
Journal: Ponatinib, Lestaurtinib and mTOR/PI3K inhibitors are promising repurposing candidates against Entamoeba histolytica. (Pubmed Central) - Mar 23, 2022
Two classes of compounds are most interesting for further investigations: the Bcr-Abl TK inhibitors, with the ponatinib (EC 0.39) as most potent and mTOR or PI3K inhibitors with 8 compounds in clinical development, of which 4 have nanomolar potency. Overall, these are promising candidates and represent a significant advance for drug development against E. histolytica.
- Preclinical evaluation of a panel of FGFR inhibitors for their normal brain and brain tumor distribution (E-Poster Website) - Mar 9, 2022 - Abstract #AACR2022AACR_6890;
The predictive parameters of brain penetration calculated based on physico-chemical properties have been estimated and shown not to correlate with the experimentally obtained neuro-pharmacokinetic values. In summary, our study provides comprehensive evaluation of neuro-pharmacokinetic behavior of seven FGFR inhibitors and delivers rationale for selection of most optimal candidates for future investigation in brain tumor clinical trials.
- | LY2874455 / Eli Lilly
Journal: Molecular mechanisms of the anti-cancer drug, LY2874455, in overcoming the FGFR4 mutation-based resistance. (Pubmed Central) - Nov 17, 2021
Interestingly, 6LF binding causes the rigidity of hinge and αD helix regions, which results in overcoming V550L induced resistance. Collectively, the results of this study would be informative for designing more efficient TKIs for more effective targeting of the FGFR signaling pathway.
- || Review, Journal: The role of fibroblast growth factor receptor (FGFR) protein-tyrosine kinase inhibitors in the treatment of cancers including those of the urinary bladder. (Pubmed Central) - Jan 6, 2021
Nintedanib, pazopanib, pemigatinib, rogaratinib, fisogatinib, and PRN1371 are FGFR inhibitors lacking drug-enzyme crystal structures...The development of FGFR inhibitors has lagged behind those of other receptor protein-tyrosine kinases. However, the FDA approval of erdafitinib for the treatment of urinary bladder cancers may stimulate additional work targeting the many other FGFR-driven neoplasms.
- || merestinib (LY2801653) / Eli Lilly, LY2874455 / Eli Lilly
Trial completion, Enrollment change, Combination therapy: Combination Merestinib and LY2874455 for Patients With Relapsed or Refractory Acute Myeloid Leukemia (clinicaltrials.gov) - Jun 30, 2020
P1, N=16, Completed, Sponsor: Jacqueline Garcia, MD
However, the FDA approval of erdafitinib for the treatment of urinary bladder cancers may stimulate additional work targeting the many other FGFR-driven neoplasms. Recruiting --> Completed | N=31 --> 16
- Erbitux (cetuximab) / Eli Lilly, EMD Serono
Drivers of secondary resistance to anti-EGFR therapy in metastatic colorectal cancer (Virtual Meeting II: E-Posters) - May 16, 2020 - Abstract #AACRII2020AACR-II_3956;
Lastly, when subjecting a Cmab SR pdx model with high endogenous overexpression of FGF13 and FGF19 to a Pan-FGF inhibitor (LY2874455) in combination with Cmab, we observed a conversion of the SR into partial response.Taken together, these results support a role of IGF2 and FGFs as candidate proteins conferring SR in an autocrine fashion in the setting of KRAS wild-type mCRC under chronic anti-EGFR treatment. Importantly, these results also suggest that potential combination therapies of Cmab and an IGF2 or FGF inhibitor could prevent establishment of SR through these pathways and offer new treatment opportunities for patients with SR mCRC.
- | LY2874455 / Eli Lilly
Journal: FGFR Signaling as a Candidate Therapeutic Target for Cancers Resistant to Carbon Ion Radiotherapy. (Pubmed Central) - Feb 8, 2020
Inhibition of FGFR using the clinically available pan-FGFR inhibitor LY2874455 sensitized multiple cancer cell lines to carbon ions at 3 Gy (RBE: relative biological effectiveness), the daily dose prescribed to the patient...Our data indicate the potential usefulness of the analytical pipeline employed in this pilot study to identify targetable mutations associated with resistance to CIRT, and of LY21874455 as a sensitizer for CIRT-resistant cancers. The results warrant validation in larger cohorts.
- Erbitux (cetuximab) / Eli Lilly, EMD Serono
Drivers of Secondary Resistance to Anti-Egfr Therapy in Metastatic Colorectal Cancer (atrium) - Jan 25, 2020 - Abstract #DKK2020DKK_2417;
Taken together, these results support a role of IGF2 and FGFs as candidate proteins conferring SR in an autocrine fashion in the setting of KRAS wild-type mCRC under chronic anti-EGFR treatment. Importantly, these results also suggest that potential combination therapies of Cmab and an IGF2 or FGF inhibitor could prevent establishment of SR and offer new treatment opportunities for patients with SR mCRC.
- Xalkori (crizotinib) / Pfizer, merestinib (LY2801653) / Eli Lilly, LY2874455 / Eli Lilly
Targeting MET and FGFR in Relapsed or Refractory Acute Myeloid Leukemia: Preclinical, Clinical, and Correlative Studies (Hall B, Level 2 (Orange County Convention Center)) - Nov 7, 2019 - Abstract #ASH2019ASH_3718;
Preliminary clinical data suggest that merestinib is tolerable and the safety of adding dose-escalated LY2874455 is under investigation . Correlative studies to evaluate the significance of changes in HGF production and in STAT3/5 target genes are on-going.
- | LY2874455 / Eli Lilly
Journal, IO Biomarker: Fibroblast Growth Factor Receptor Inhibition induces loss of matrix MCL1 and necrosis in Cholangiocarcinoma. (Pubmed Central) - Sep 18, 2019
Cellular depletion of MCL1 results in cell death of the cancer cells by a process characterized by cell rupture. Cell death by this process can stimulate the immune system and has implications for combination therapy employing receptor inhibition with immunotherapy.
- LY2874455 / Eli Lilly
FGF19 promotes esophageal squamous cell carcinoma progression by inhibiting autophagy (Poster Area (Hall 4)) - Sep 11, 2019 - Abstract #ESMO2019ESMO_2670;
Using FGFR inhibitor may represent an effective strategy to suppress FGF19 amplificated ESCC development and progression. Legal entity responsible for the study: The authors.
- merestinib (LY2801653) / Eli Lilly, LY2874455 / Eli Lilly
Enrollment open, Trial initiation date, Combination therapy: Combination Merestinib and LY2874455 for Patients With Relapsed or Refractory Acute Myeloid Leukemia (clinicaltrials.gov) - Aug 11, 2017
P1, N=31, Recruiting, Sponsor: Jacqueline Garcia, MD
Legal entity responsible for the study: The authors. Not yet recruiting --> Recruiting | Initiation date: May 2017 --> Aug 2017
- | merestinib (LY2801653) / Eli Lilly, LY2874455 / Eli Lilly
New P1 trial, Combination therapy: Combination Merestinib and LY2874455 for Patients With Relapsed or Refractory Acute Myeloid Leukemia (clinicaltrials.gov) - Apr 24, 2017
P1, N=31, Not yet recruiting, Sponsor: Jacqueline Garcia, MD
- ||| LY2874455 / Eli Lilly
Trial completion, Metastases: A Phase 1 Study of LY2874455 in Participants With Advanced Cancer (clinicaltrials.gov) - Feb 27, 2015
P1, N=94, Completed, Sponsor: Eli Lilly and Company
Not yet recruiting --> Recruiting | Initiation date: May 2017 --> Aug 2017 Active, not recruiting --> Completed
- || LY2874455 / Eli Lilly
Trial primary completion date, Metastases: A Phase 1 Study of LY2874455 in Participants With Advanced Cancer (clinicaltrials.gov) - May 11, 2014
P1, N=100, Active, not recruiting, Sponsor: Eli Lilly and Company
Active, not recruiting --> Completed Trial primary completion date: Jun 2014 --> Sep 2014
- | LY2874455 / Eli Lilly
Trial completion date, Metastases: A Phase 1 Study of LY2874455 in Participants With Advanced Cancer (clinicaltrials.gov) - May 11, 2014
P1, N=100, Active, not recruiting, Sponsor: Eli Lilly and Company
Trial primary completion date: Jun 2014 --> Sep 2014 Trial completion date: Nov 2014 --> Sep 2014
- || LY2874455 / Eli Lilly
Enrollment closed, Metastases: A Phase 1 Study of LY2874455 in Participants With Advanced Cancer (clinicaltrials.gov) - Mar 18, 2014
P1, N=100, Active, not recruiting, Sponsor: Eli Lilly and Company
Trial completion date: Nov 2014 --> Sep 2014 Recruiting --> Active, not recruiting