A5102941075- HER2/EGFR in Cancer Research
- Monoclonal and Polyclonal Antibodies Research
- Cancer therapeutics and mechanisms
- Estrogen and related hormone effects
- Receptor Mechanisms and Signaling
- Radiopharmaceutical Chemistry and Applications
- Chemical Synthesis and Analysis
- Click Chemistry and Applications
Zymeworks (Canada)
2023-2024
Abstract In recent years, the field of antibody drug conjugates (ADC) has seen a resurgence, largely driven by clinical benefit observed in patients treated with ADCs incorporating camptothecin-based topoisomerase I inhibitor payloads. Herein, we present development novel camptothecin ZD06519 (FD1), which been specifically designed for its application as an ADC payload. A panel analogs different substituents at C-7 and C-10 positions core was prepared tested vitro. Selected compounds...
Abstract Background: Folate Receptor alpha (FRα) is a validated cancer target that prevalently expressed in multiple cancers with high unmet need, including ovarian and other gynecological cancers, NSCLC, endometrial TNBC. Due to FRα’s favorable expression profile, antibody-drug conjugates (ADCs) are being explored this setting. Here we present the preclinical characterization of new anti-FRα ADC, ZW191. ZW191 bystander active antibody drug conjugate (ADC) comprised humanized IgG1 conjugated...
Synthetic analogs based on the DNA bis-intercalating natural product peptides sandramycin and quinaldopeptin were investigated as antibody drug conjugate (ADC) payloads. Synthesis, biophysical characterization, in vitro potency of 34 new are described. Conjugation an initial drug-linker derived from a novel peptide produced ADC that was hydrophobic prone to aggregation. Two strategies employed improve physiochemical properties: addition solubilizing group linker use enzymatically cleavable...
<p>Supplementary Figure S2 shows the chemical stability of FD1 (ZD06519)</p>
<p>Supplementary Figure S3 shows the in vitro cytotoxicity assessment of trastuzumab-ADCs both two-dimensional (2D) and three-dimensional (3D) spheroid assays</p>
<p>Synthesis and characterization of free drugs drug-linkers</p>
<p>Supplementary Figure S4 shows the pharmacokinetic analysis of ADCs (total antibody PK) from tolerability study in rats</p>
<p>Supplementary Figure S4 shows the pharmacokinetic analysis of ADCs (total antibody PK) from tolerability study in rats</p>
<p>Synthesis and characterization of free drugs drug-linkers</p>
<p>HPLC-HIC, LC-MS, HPLC-SEC, residual free drug analysis, and endotoxin levels of ADCs</p>
<div>Abstract<p>In recent years, the field of antibody drug conjugates (ADC) has seen a resurgence, largely driven by clinical benefit observed in patients treated with ADCs incorporating camptothecin-based topoisomerase I inhibitor payloads. Herein, we present development novel camptothecin ZD06519 (FD1), which been specifically designed for its application as an ADC payload. A panel analogs different substituents at C-7 and C-10 positions core was prepared tested <i>in...
<p>Supplementary Figure S3 shows the in vitro cytotoxicity assessment of trastuzumab-ADCs both two-dimensional (2D) and three-dimensional (3D) spheroid assays</p>
<p>Supplementary Figure S1 shows the murine plasma stability of T-DL4 and T-DL13</p>
<p>Supplementary Figure S1 shows the murine plasma stability of T-DL4 and T-DL13</p>
<div>Abstract<p>In recent years, the field of antibody drug conjugates (ADC) has seen a resurgence, largely driven by clinical benefit observed in patients treated with ADCs incorporating camptothecin-based topoisomerase I inhibitor payloads. Herein, we present development novel camptothecin ZD06519 (FD1), which been specifically designed for its application as an ADC payload. A panel analogs different substituents at C-7 and C-10 positions core was prepared tested <i>in...
<p>HPLC-HIC, LC-MS, HPLC-SEC, residual free drug analysis, and endotoxin levels of ADCs</p>
<p>Supplementary Figure S2 shows the chemical stability of FD1 (ZD06519)</p>