brilanestrant (GDC-0810) / Roche 
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  • ||||||||||  brilanestrant (GDC-0810) / Roche
    Journal:  Tuning Bottlebrush Polymer Architecture and Composition of Poly(acrylic acid) Improves GDC-0810 Drug Solubility Maintenance. (Pubmed Central) -  Dec 8, 2025   
    The ASDs containing 40 wt % GDC-0810 exhibited a linear performance trend, correlating improved performance to increased carboxylic acid content in bottlebrush polymers, indicating the importance of electrostatic repulsions with the weak acid API on dissolution efficacy. This work demonstrates the importance of architecture, placement, and amount of carboxylate groups in excipient performance.
  • ||||||||||  brilanestrant (GDC-0810) / Roche
    Journal:  Drug-Polymer Nanodroplet Formation and Morphology Drive Solubility Enhancement of GDC-0810. (Pubmed Central) -  Apr 18, 2024   
    This is likely due to strong polymer-drug noncovalent interactions and the compaction of GDC-0810 along the PVPVA bottlebrush backbone. Overall, it was observed that the most effective formulations had a hydrodynamic radius less than 25 nm with tightly compacted nanodroplet morphologies.
  • ||||||||||  brilanestrant (GDC-0810) / Roche
    Journal:  Utilizing Molecular Simulations to Examine Nanosuspension Stability. (Pubmed Central) -  Jan 23, 2024   
    To test these ideas prospectively, we applied our model to an uncharacterized drug compound, GDC-0810...To avoid computationally expensive simulations in the future, we extended our model by showing that simple, two-dimensional properties of single drug molecules can be used to rationalize nanosuspension designs without simulations. In all, our work demonstrates how computational tools can provide molecular insight into drug-excipient interactions and aid in rational formulation design.
  • ||||||||||  Journal:  Development of an assay pipeline for the discovery of novel small molecule inhibitors of human glutathione peroxidases GPX1 and GPX4. (Pubmed Central) -  Jun 7, 2023   
    Two compounds (metamizole sodium and isoniazid sodium methanesulfate) inhibited all three GPXs but not TXNRD1, while 2,3-dimercaptopropanesulfonate, PI4KIII beta inhibitor 3, SCE-2174 and cefotetan sodium inhibited all tested selenoproteins (but not GR)...With this approach, we could indeed identify novel GPX1/GPX2- or GPX4-specific inhibitors, thus presenting a validated pipeline for future identification of specific selenoprotein-targeting agents. Our study also identified GPX1/GPX2, GPX4 and/or TXNRD1 as targets for several previously developed pharmacologically active compounds.
  • ||||||||||  brilanestrant (GDC-0810) / Roche
    End-Group Modified Bottlebrush Copolymers to Deliver Active Pharmaceutical Ingredients (In-Person Room (Virtual Room)) -  Jan 28, 2022 - Abstract #ACSSp2022ACS_Sp_9887;    
    Therefore, we thoroughly characterized the phenotype of amorphous nanostructures formed in solution during ASD dissolution between an orally administered breast cancer therapeutic, GDC-0810, and a library of commercial linear polymer and end-group modified bottlebrush copolymer excipients. The resulting insight was then used to interpret the differences in bioavailability observed through in vivo pharmacokinetic studies and in vitro permeation assays as a function of nanostructure formation.
  • ||||||||||  brilanestrant (GDC-0810) / Roche
    Journal:  Bioactivation of α,β-Unsaturated Carboxylic Acids Through Acyl Glucuronidation. (Pubmed Central) -  Sep 15, 2021   
    Significance Statement Acyl glucuronidation of the α,β-unsaturated carboxylic acid in GDC-0810 activates the conjugated alkene towards nucleophilic addition by GSH or other reactive thiols. This is the first example that a bioactivation mechanism could lead to protein covalent binding to α,β-unsaturated carboxylic acid compounds.
  • ||||||||||  tamoxifen / Generic mfg.
    [VIRTUAL] Bottlebrush polymer excipients to improve the solubility and delivery of an orally administered breast cancer therapeutic (Room: Zoom Room 21) -  Aug 13, 2021 - Abstract #ACSFall2021ACS_Fall_1956;    
    Beyond solubility enhancement, by synthetically controlling the surface functionality of unimolecular drug-loaded micelle-like nanoparticles, we investigated how mucoadhesive versus non-mucoadhesive end-groups affected the delivery of GDC-0810 with in vivo studies. A thorough understanding of excipient-drug interactions in vitro and in vivo will be key to optimize the sequestration, solubilization, and delivery of future impactful active payloads.
  • ||||||||||  Livalo (pitavastatin) / Kowa, Eli Lilly
    [VIRTUAL] Targeting ESR1 in breast cancer treatment: Repurposing of statins () -  Jul 22, 2021 - Abstract #ESMO2021ESMO_1586;    
    The study indicates that the drugs, simvastatin, lovastatin and mevastatin could be effective drugs in breast cancer treatment. However, further studies including in vitro and in vivo tests will be required to investigate their safety, efficacy and dosing profiles.
  • ||||||||||  GDC-9545 / Roche
    [VIRTUAL] GDC-9545: Discovery of an oral estrogen receptor antagonist, degrader, and immobilizer for the treatment of ER+ breast cancer patients (Virtual Meeting: All Session Times Are U.S. EDT) -  Apr 13, 2020 - Abstract #AACRI2020AACR-I_82;    
    These endocrine resistant tumors often continue to depend on ERα for growth and survival, as evidenced by their sensitivity to the selective estrogen receptor antagonist and degrader, fulvestrant...We have reported previously of our first and second generations of orally available ERα ligands, GDC-0810 and GDC-0927 respectively...It is orally bioavailable and has high safety margins in preclinical species. GDC-9545 is currently in active clinical testing.
  • ||||||||||  OP-1250, an oral complete estrogen receptor antagonist (CERAN) that shrinks ER-positive breast tumors in xenograft models (Atrium) -  Feb 28, 2020 - Abstract #BOP2020BOP_79;    
    Fulvestrant (FASLODEX) is the most effective endocrine therapy for estrogen receptor positive (ER+) metastatic breast cancer (MBC)...In contrast to CERANs, selective estrogen receptor modulators (SERMs) such as tamoxifen efficiently shut off AF2 signaling (turned on by estradiol), but incompletely antagonize AF1, a function that is turned on by multiple cell signaling pathways and shown to play a role in the development of endocrine resistance...In our assay several SERDs under clinical investigation, including AZD9496 and GDC-0810, were identified as SERMs that exhibited ER-mediated agonism on genes dependent on AF1 activity...These results suggest that OP-1250 has potential to be a superior compound to treat ER+ MBC, especially in patients whose tumors allow high activity of AF1 and including those with activating mutations ins ESR1. We expect to bring OP-1250 into the clinic shortly.
  • ||||||||||  brilanestrant (GDC-0810) / Roche
    Biomarker, Clinical, PK/PD data, Journal:  Effect of OATP1B1/1B3 Inhibitor GDC-0810 on the Pharmacokinetics of Pravastatin and Coproporphyrin I/III in Healthy Female Subjects. (Pubmed Central) -  Dec 6, 2019   
    Based on the magnitude of change in this drug-drug interaction study, dose adjustments for pravastatin (and other OATP1B1/1B3 substrates) were not considered necessary when administered with GDC-0810. Retrospectively, the endogenous biomarkers of OATP1B1/1B3, coproporphyrin I and III, were also measured and showed changes comparable to those of pravastatin, indicating their utility in detecting weak inhibition of OATP1B1/1B3 in the clinical setting.
  • ||||||||||  rifampicin / generics
    Biomarker, Journal:  Quantitative prediction of OATP-mediated drug-drug interactions with model-based analysis of endogenous biomarker kinetics. (Pubmed Central) -  Oct 29, 2019   
    Clinical DDIs between pravastatin and these inhibitors were predicted using physiologically-based pharmacokinetic (PBPK) models coupled with the estimated in vivo K and predicted magnitude matched well with the observed DDIs. In conclusion, model-based analysis of the CPI profile has the potential to quantitatively predict liability of a new molecular entity (NME) as an OATP1B inhibitor early in drug development.
  • ||||||||||  AZD9496 / AstraZeneca, brilanestrant (GDC-0810) / Roche, Faslodex (fulvestrant) / AstraZeneca
    Preclinical development of OP-1250, an oral complete estrogen receptor antagonist (CERAN) that shrinks ER-positive breast tumors in xenograft models (Hall 1 - Poster Session 5) -  Sep 25, 2019 - Abstract #SABCS2019SABCS_634;    
    Fulvestrant (FASLODEX) is the most effective endocrine therapy for estrogen receptor positive (ER+) metastatic breast cancer (MBC)...In our assay several SERDs under clinical investigation, including AZD9496 and GDC-0810, were identified as SERMs that exhibited ER-mediated agonism on genes dependent on AF1 activity...These results suggest that OP-1250 has potential to be a superior compound to treat ER+ MBC, especially in patients whose tumors allow high activity of AF1 and including those with activating mutations ins ESR1. We expect to bring OP-1250 into the clinic shortly.
  • ||||||||||  brilanestrant (GDC-0810) / Roche
    Journal:  Synthesis of Selective Estrogen Receptor Degrader GDC-0810 via Stereocontrolled Assembly of a Tetrasubstituted All-Carbon Olefin. (Pubmed Central) -  Sep 8, 2019   
    We report an efficient synthesis of GDC-0810 based on a sequence involving a highly stereoselective lithium tert-butoxide mediated enolization-tosylation (≥95:5 E:Z) and a Pd-catalyzed Suzuki‒Miyaura cross-coupling as key steps. Global deprotection, pyrrolidine salt formation, and final active pharmaceutical ingredient (API) form control / isolation produced GDC-0810 free acid in a 40% overall yield with >99.0% purity as ascertained by HPLC analysis.
  • ||||||||||  Journal:  Novel Selective Estrogen Receptor Downregulators (SERDs) Developed Against Treatment-Resistant Breast Cancer. (Pubmed Central) -  Jun 19, 2017   
    Treatment-resistant (TR) ER+ cell lines (MCF-7:5C and MCF-7:TAM1) were used for optimization, followed by validation in the parent endocrine-dependent cell line (MCF-7:WS8), in 2D and 3D cultures, using ERα in-cell westerns, ERE-luciferase, and cell viability assays, with 2 (GDC-0810/ARN-810) used for comparison. Two BT SERDs with superior in vitro activity to 2 were studied for bioavailability and shown to cause regression of a TR, endocrine-independent ER+ xenograft superior to 2.
  • ||||||||||  brilanestrant (GDC-0810) / Roche
    Enrollment open, Trial initiation date:  Study to Investigate the Effect of Formulation and Food on the Pharmacokinetics of GDC-0810 (clinicaltrials.gov) -  Apr 27, 2016   
    P1,  N=48, Recruiting, 
    Phase classification: P2 --> P1a/1b | N=141 --> 195 | Trial primary completion date: Jul 2017 --> Dec 2017 Not yet recruiting --> Recruiting | Initiation date: Jun 2016 --> Dec 2015