linifanib (ABT-869) / AbbVie 
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  • ||||||||||  Biomarker, Journal:  Development and Validation of a Comprehensive Prognostic and Depression Risk Index for Gastric Adenocarcinoma. (Pubmed Central) -  Oct 16, 2024   
    With the Genomics of Drug Sensitivity in Cancer database, we found that the gastric adenocarcinoma patients with high risk-score may be sensitive to Pazopanib, XMD8.85, Midostaurin, HG.6.64.1, Elesclomol, Linifanib, AP.24534, Roscovitine, Cytarabine, and Axitinib. The gene signature consisting of the NDUFA4L2, ANKRD45, and AQP3 genes is a promising biomarker to distinguish the prognosis, the molecular and immune characteristics, the depressive risk, and the therapy candidates for gastric adenocarcinoma patients.
  • ||||||||||  linifanib (ABT-869) / AbbVie
    Journal:  The VEGFR/PDGFR tyrosine kinase inhibitor, ABT-869, blocks necroptosis by targeting RIPK1 kinase. (Pubmed Central) -  May 17, 2023   
    We applied a suite of cellular, biochemical and biophysical analyses to pinpoint the apical necroptotic kinase, RIPK1, as the target of ABT-869 inhibition. Our study adds to the repertoire of established protein kinase inhibitors that additionally target RIPK1 and raises the prospect that serendipitous targeting of necroptosis signalling may contribute to their clinical efficacy in some settings.
  • ||||||||||  linifanib (ABT-869) / AbbVie
    Journal:  Dual-Bioorthogonal Catalysis by a Palladium Peptide Complex. (Pubmed Central) -  Mar 11, 2023   
    Our work shows how a palladium-peptide homogeneous catalyst can simultaneously mediate two types of chemistry to synthesize anticancer drugs in human cells. Methyl salicylate palladium LLEYLKR peptide (2-Pd) succeeded to simultaneously produce paclitaxel by depropargylation, and linifanib by Suzuki-Miyaura cross-coupling in cell culture, thereby achieving combination therapy on non-small-cell lung cancer (NSCLC) A549 cells.
  • ||||||||||  linifanib (ABT-869) / AbbVie
    Journal:  Repositioning linifanib as a potent anti-necroptosis agent for sepsis. (Pubmed Central) -  Feb 12, 2023   
    Our preclinical evidence using an integrated in silico and experimental drug repositioning approach supports the potential clinical utility of linifanib in septic patients. Further clinical validation is now warranted.
  • ||||||||||  Efficacy and safety of frontline systemic therapy for advanced hepatocellular carcinoma (aHCC): A network meta-analysis of landmark phase III trials. (Available On Demand; Poster Board No. D1) -  Dec 13, 2022 - Abstract #ASCOGI2023ASCO_GI_439;    
    These tested respectively: sorafenib (S) vs placebo (SHARP and Asia Pacific), sunitinib (Sun) vs S, brivanib (Bri) vs S, linifanib (Lin) vs S, lenvatinib (L) vs S, nivolumab (Nivo) vs S, atezolizumab+bevacizumab (A+B) vs S, sintilimab+IBI-305 vs S, durvalumab+tremelimumab (D+T) vs S, atezolizumab+cabozantinib (A+C) vs S, donafenib vs S, camrelizumab plus rivoceranib (C+R) vs S, pembrolizumab plus lenvatinib (P+L) vs L, and tislelizumab (TS) vs S as first line treatments for aHCC... Combination of ICI + anti-VEGF antibodies leads to the greatest OS benefit compared to sorafenib, whereas ICI + kinase inhibitor regimens are associated with greater PFS benefit at the cost of higher toxicity rates.
  • ||||||||||  Biomarker, Journal, Tumor Mutational Burden, Pan tumor:  A Pan-Cancer Analysis Reveals CLEC5A as a Biomarker for Cancer Immunity and Prognosis. (Pubmed Central) -  Aug 22, 2022   
    CLEC5A overexpresses in multiple cancers in contrast to normal tissues, and high CLEC5A expression predicts poor prognosis of patients and immune infiltration. CLEC5A is a potential prognostic biomarker of diverse cancers and a target for anti-tumor therapy.
  • ||||||||||  Systemic Therapy in Advanced Hepatocellular Carcinoma : Where are we heading? () -  May 30, 2022 - Abstract #SIR2022SIR_2038;    
    After Sorafenib demonstrated improved overall survival (OS) in SHARP and Asia Pacific trials over placebo (8,9) many other phase lll trials have been conducted with other multi kinase inhibitors like sunitinib, brivanib and linifanib; none of which yielded significant results compared to sorafenib (10-12)...Tyrosine kinase inhibitors Regorafenib and Cabozantinib have shown significant improvement in survival, in RESORCE and CELESTIAL trials respectively as second line treatment after sorafenib failures, radiological progression or intolerance in patients. While a lot of progress has been made in increasing survival of patients with advanced HCC, the ongoing trials will further change the treatment paradigm significantly for HCC.
  • ||||||||||  Inlyta (axitinib) / Pfizer, linifanib (ABT-869) / AbbVie, Gilotrif (afatinib) / Boehringer Ingelheim
    Enrollment change, Trial completion date, Trial withdrawal, Trial primary completion date:  ELTA: Safety, Tolerability and Efficacy of Vaginal Suppositories for Treatment of the Endometriosis (clinicaltrials.gov) -  Oct 29, 2021   
    P1/2,  N=0, Withdrawn, 
    More prospective randomized study designs comparing type 1 and 2 inhibitors in the R/R and de novo setting are needed. N=94 --> 0 | Trial completion date: Jan 2023 --> Oct 2021 | Suspended --> Withdrawn | Trial primary completion date: Dec 2022 --> Oct 2021
  • ||||||||||  Journal:  Systemic therapy for advanced hepatocellular carcinoma: targeted therapies. (Pubmed Central) -  Oct 22, 2021   
    Since the United States Food and Drug Administration (US FDA) approval of sorafenib in 2008, targeted therapies such as sunitinib, tivantinib, brivanib, erlotinib, and linifanib; monoclonal antibody- bevacizumab showed no meaningful improvement in treatment of HCC...Targeted therapy with lenvatinib, cabozantinib, and regorafenib; monoclonal antibody ramucirumab; immunotherapies nivolumab and pembrolizumab have demonstrated promising results in the clinical trials. The current work outlines the molecular mechanisms and tumorigenesis of HCC, a detailed discussion of the trial results of the approved therapies in HCC, future perspectives and potential options to overcome the challenges of systemic therapy in HCC.
  • ||||||||||  Nexavar (sorafenib) / Bayer, Amgen
    Journal:  Nitrogen Containing Heterocycles as Anticancer Agents: An Overview. (Pubmed Central) -  Jun 8, 2021   
    As per FDA databases nitrogen-based heterocycles in the drug design is almost 60% of unique smallmolecule drugs. Some of the nitrogen containing heterocyclic anti-cancer drugs are Axitinib, Bosutinib, Cediranib, Dasatanib (Sprycel®), Erlotinib (Tarceva®), Gefitinib (Iressa®), Imatinib (Gleevec®), Lapatinib (Tykerb®), Linifanib, Sorafenib (Nexavar®), Sunitinib (Sutent®), Tivozanib etc. In the present review, we shall focus on the overview of nitrogen containing heterocyclic active compounds as anti-cancer agents.
  • ||||||||||  Opdivo (nivolumab) / Ono Pharma, BMS, Cabometyx (cabozantinib tablet) / Takeda, Exelixis, Ipsen
    [VIRTUAL] Systemic Therapy in Advanced Hepatocellular Carcinoma : Where are we heading? () -  Feb 24, 2021 - Abstract #SIR2021SIR_865;    
    After Sorafenib demonstrated improved overall survival (OS) in SHARP and Asia Pacific trials over placebo (8,9) many other phase lll trials have been conducted with other multi kinase inhibitors like sunitinib, brivanib and linifanib; none of which yielded significant results compared to sorafenib (10-12)...Tyrosine kinase inhibitors Regorafenib and Cabozantinib have shown significant improvement in survival, in RESORCE and CELESTIAL trials respectively as second line treatment after sorafenib failures, radiological progression or intolerance in patients. While a lot of progress has been made in increasing survival of patients with advanced HCC, the ongoing trials will further change the treatment paradigm significantly for HCC.
  • ||||||||||  Inlyta (axitinib) / Pfizer, linifanib (ABT-869) / AbbVie, Gilotrif (afatinib) / Boehringer Ingelheim
    Trial completion date, Trial suspension, Trial primary completion date:  ELTA: Safety, Tolerability and Efficacy of Vaginal Suppositories for Treatment of the Endometriosis (clinicaltrials.gov) -  Feb 21, 2021   
    P1/2,  N=94, Suspended, 
    While a lot of progress has been made in increasing survival of patients with advanced HCC, the ongoing trials will further change the treatment paradigm significantly for HCC. Trial completion date: Jan 2022 --> Jan 2023 | Not yet recruiting --> Suspended | Trial primary completion date: Dec 2021 --> Dec 2022
  • ||||||||||  linifanib (ABT-869) / AbbVie
    Preclinical, Journal:  The Influence of Liquid Intake on the Performance of an Amorphous Solid Dispersion in Rats. (Pubmed Central) -  Feb 7, 2021   
    The aim of this rat study was to investigate the effect of liquid intake on the oral bioavailability of an amorphous solid dispersion (ASD) containing the poorly water-soluble compound ABT-869...Yet, our findings emphasize that the amount of liquid co-administered with oral enabling formulations can have an impact on the bioavailability. The administration regime used in animal studies should therefore be considered carefully.
  • ||||||||||  linifanib (ABT-869) / AbbVie, Tafinlar (dabrafenib) / Novartis
    Journal:  Feature selection strategies for drug sensitivity prediction. (Pubmed Central) -  Dec 16, 2020   
    Extending the drug-dependent features with gene expression signatures yields the most predictive models for 60 drugs, with the best performing example of Dabrafenib...Small feature sets selected using prior knowledge are more predictive for drugs targeting specific genes and pathways, while models with wider feature sets perform better for drugs affecting general cellular mechanisms. Appropriate feature selection strategies facilitate the development of interpretable models that are indicative for therapy design.
  • ||||||||||  linifanib (ABT-869) / AbbVie
    Biomarker, Journal:  OncomiR-10b hijacks the small molecule inhibitor linifanib in human cancers. (Pubmed Central) -  Oct 25, 2019   
    In conclusion, our study describes an effective strategy to screen for small molecule inhibitors of miRNAs. We further propose that miR-10b expression levels, due to the newly described "hijacking" effect, may be used as a biomarker to select patients for linifanib treatment.
  • ||||||||||  Inlyta (axitinib) / Pfizer, linifanib (ABT-869) / AbbVie, Gilotrif (afatinib) / Boehringer Ingelheim
    Trial completion date, Trial primary completion date:  ELTA: Safety, Tolerability and Efficacy of Vaginal Suppositories for Treatment of the Endometriosis (clinicaltrials.gov) -  Jul 23, 2019   
    P1/2,  N=94, Not yet recruiting, 
    We further propose that miR-10b expression levels, due to the newly described "hijacking" effect, may be used as a biomarker to select patients for linifanib treatment. Trial completion date: Sep 2018 --> Jan 2022 | Trial primary completion date: Aug 2018 --> Dec 2021
  • ||||||||||  linifanib (ABT-869) / AbbVie, Nexavar (sorafenib) / Bayer, Amgen
    Preclinical, Journal, PARP Biomarker, IO Biomarker:  Cytotoxic and apoptotic effects of novel pyrrolo[2,3-d]pyrimidine derivatives containing urea moieties on cancer cell lines. (Pubmed Central) -  Jun 28, 2019   
    Compound 10b and 93 showed the strong cytotoxic activity against MCF-7 and A549 cells with IC50 value of 1.66 µM and 4.55 µM, respectively.Flow cytometry data suggest that the cytotoxic activity of the compounds on cancer cells might be mediated by apoptosis revealing a significant increase in the percentage of late apoptotic cells and causing a cell cycle arrest at different stages. .Western blot analysis of apoptosis marker demonstrated that these compounds induce apoptosis through the intrinsic pathway.