- |||||||||| NEO2734 / Epigenetix, inobrodib (CCS1477) / CellCentric
Review, Journal: Characteristics of anticancer activity of CBP/p300 inhibitors - Features of their classes, intracellular targets and future perspectives of their application in cancer treatment. (Pubmed Central) - Apr 15, 2024
However, none of the described inhibitors is perfectly specific to CBP/p300 since they share similarity of a key functional domains with other enzymes, which are critically associated with cancer progression and their antagonists demonstrate remarkable clinical efficacy in cancer therapy. Therefore, we revise the possible and clinically relevant off-targets of CBP/p300 inhibitors that can be blocked simultaneously with CBP/p300 thereby improving the anticancer potential of CBP/p300 inhibitors and pharmacokinetic predicting data such as absorption, distribution, metabolism, excretion (ADME) and toxicity.
- |||||||||| NEO2734 / Epigenetix
Journal: Co-targeting BET, CBP, and p300 inhibits neuroendocrine signalling in androgen receptor-null prostate cancer. (Pubmed Central) - Apr 5, 2024
Therefore, we revise the possible and clinically relevant off-targets of CBP/p300 inhibitors that can be blocked simultaneously with CBP/p300 thereby improving the anticancer potential of CBP/p300 inhibitors and pharmacokinetic predicting data such as absorption, distribution, metabolism, excretion (ADME) and toxicity. A combined inhibitor of these three proteins, NEO2734, reduced the growth of both AR-positive and AR-null organoids, as measured by changes in viability, size, and composition..
- |||||||||| NEO2734 / Epigenetix
The interaction of radiotherapy and dual inhibition of BET and HAT/p300 in colorectal cancer. (Level 1, West Hall; Poster Bd # J12) - Dec 6, 2023 - Abstract #ASCOGI2024ASCO_GI_791;
EP31670 enhanced RT-induced growth arrest, reduced proliferation, and enhanced cell death in HCT116 CRC cells in synergy with the RT. Additional preclinical studies, in vivo studies, and eventual clinical studies can be conducted to further exploit this synergistic interaction.
- |||||||||| NEO2734 / Epigenetix
Targeting Oncogenic Enhancers in ASXL1-Mutant Chronic Myelomonocytic Leukemia (Halls G-H (San Diego Convention Center)) - Nov 3, 2023 - Abstract #ASH2023ASH_1820;
In a model system, the disruption of an enhancer predicted to govern the expression of the leukemogenic driver HOXA9, led to a significant down-regulation of HOXA9 expression. Pharmacologically disrupting the oncogenic interaction at such enhancers with EP31670 in primary patient samples led to significant therapeutic effects at nanomolar drug concentrations in a genotype-specific manner.
- |||||||||| NEO2734 / adMare BioInnovations, Epigenetix, linsitinib (ASP7487) / Sling Therap
Journal: Automation, live-cell imaging, and endpoint cell viability for prostate cancer drug screens. (Pubmed Central) - Oct 14, 2023
In addition, we found that insulin-like growth factor-1 receptor (IGF-1R) inhibitor linsitinib is a potential pharmacological agent against highly lethal and drug-resistant NEPC NCI-H660 cells. This protocol can be employed across other cancer types and represents an adaptable strategy to optimize assay-specific cell growth conditions and simultaneously assess drug efficacy across multiple cell lines.
- |||||||||| NEO2734 / adMare BioInnovations, Epigenetix
Enrollment open, Trial initiation date, Metastases: Dual BET and CBP/p300 Inhibitor in Patients With Targeted Advanced Solid Tumors (clinicaltrials.gov) - Feb 8, 2023
P1, N=50, Recruiting,
AR-V-mediated SLC7A11 expression represents a mechanism coupling ferroptosis resistance to PCa progression. Not yet recruiting --> Recruiting | Initiation date: Sep 2022 --> Dec 2022
- |||||||||| GW842166 / GSK, ART27.13 / Artelo Biosci, adMare BioInnovations
Review, Journal: Cannabis and orofacial pain: a systematic review. (Pubmed Central) - Jun 29, 2022
Further research is warranted to explore and substantiate the therapeutic role of CBPMs in the context of orofacial pain and inflammation. As evidence supporting their use expands, healthcare professionals should pay close attention to outcomes and changes to legislation that may impact and potentially benefit their patients.
- |||||||||| NEO2734 / adMare BioInnovations, Epigenetix
Journal: Targeting CDCP1 gene transcription coactivated by BRD4 and CBP/p300 in castration-resistant prostate cancer. (Pubmed Central) - Jun 9, 2022
Our biochemical and structural analyses further showed that NEO2734, a dual-inhibitor targeting BRD4 and p300 bromodomains exhibits greater efficacy than single inhibitors for BRD4 or CBP/p300 in suppressing CDCP1 transcriptional expression and its downstream signaling pathways in CRPC cell proliferation and metastasis. Our study illustrates that targeting CDCP1 through dual-inhibition of BRD4 and CBP/p300 represents a synergistic therapeutic strategy for new treatment of CRPC.
- |||||||||| NEO2734 / adMare BioInnovations, Epigenetix, Ibrance (palbociclib) / Pfizer
Journal: HDAC5 loss impairs RB repression of pro-oncogenic genes and confers CDK4/6 inhibitor resistance in cancer. (Pubmed Central) - Jun 30, 2021
HDAC5 loss also conferred resistance to CDK4/6 inhibitors such as Palbociclib in prostate and breast cancer cells in vitro and prostate tumors in vivo, but this effect was overcome by the BET-CBP/p300 dual inhibitor NEO2734. Our findings reveal an unknown role of HDAC5 in RB-mediated histone deacetylation and gene repression and define a new mechanism modulating CDK4/6 inhibitor therapeutic sensitivity in cancer cells.
- |||||||||| NEO2734 / adMare BioInnovations, Epigenetix, CBP/P300 inhibitor / adMare BioInnovations, Epigenetix
Journal: Antitumor activity of the dual BET and CBP/EP300 inhibitor NEO2734. (Pubmed Central) - May 15, 2021
However, NEO2734 was more potent than single-agent BET or CBP/EP300 inhibitors alone. In conclusion, NEO2734 is a novel antitumor compound that shows preferential activity in lymphomas, leukemias, and prostate cancers.
- |||||||||| enzalutamide capsule / Generic mfg.
Journal: A noncanonical AR addiction drives enzalutamide resistance in prostate cancer. (Pubmed Central) - Apr 7, 2021
Consistent with the finding that ARBS-gained loci are highly enriched with H3K27ac modification, ENZ-resistant PCa cells, organoids, xenografts and PDXs are hyper-sensitive to NEO2734, a dual inhibitor of BET and CBP/p300 proteins. These results not only reveal a noncanonical AR function in acquisition of ENZ resistance, but also posit a treatment strategy to target this vulnerability in ENZ-resistant CRPC.
- |||||||||| NEO1132 / EPIGeNE, Epigenetix, etoposide IV / Generic Mfg.
Novel dual BET/p300 bromodomain inhibitors therapeutically inhibit BRD4-NUT driven NUT Carcinomas (Board 14: Level 2 - Hall D) - Sep 18, 2019 - Abstract #AACRNCIEORTC2019AACR_NCI_EORTC_236;
These data support our hypothesis that p300 recruitment is necessary for the oncogenic functions of BRD4-NUT and dual targeting of BET and p300 BDs represents a promising therapeutic option for NC patients. Future studies are necessary to determine the relative contribution of BET versus p300 BD inhibition to preventing NC growth by NEO compounds.
- |||||||||| NEO1132 / EPIGeNE, Epigenetix, JQ-1 / Roche, molibresib (GSK525762) / GSK
NEO2734, a novel dual BET and P300/CBP bromodomain inhibitor, is more active in NUT midline carcinoma than single agent BET or P300/CBP inhibitors (Board 8: Level 2 - Hall D) - Sep 18, 2019 - Abstract #AACRNCIEORTC2019AACR_NCI_EORTC_231;
ResultConsidering the important roles of BET proteins and P300 in NMC, two NMC-cell lines (1015 and 14169, C. French: Brigham and Women’s Hospital) were treated with dual BET and P300/CBP inhibitors NEO2734 and NEO1131 (Epigene Therapeutics Inc), BET inhibitors JQ1 and iBET155 (GSK525762) (Sigma-Aldrich) and P300/CBP inhibitor CPI-637 (MedChem Express) for comparison...We also observed the presence of two different cell populations (adherent and suspension cells) in both NMC cell lines with adherent cells being more resistant to NEO2734, Differences in the responses to NEO2734 in NMC are being studied to molecularly identify biomarkers of resistance. These data support the inclusion of patients with NMC in clinical studies of NEO2734.
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