A5033698777- HER2/EGFR in Cancer Research
- Monoclonal and Polyclonal Antibodies Research
- Cancer therapeutics and mechanisms
- Receptor Mechanisms and Signaling
- Estrogen and related hormone effects
- Advanced Breast Cancer Therapies
- Medical Imaging and Pathology Studies
- Click Chemistry and Applications
- Radiopharmaceutical Chemistry and Applications
- Glycosylation and Glycoproteins Research
- Amino Acid Enzymes and Metabolism
- Parathyroid Disorders and Treatments
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...
Abstract Background: Folate Receptor alpha (FRa) is a validated cell surface cancer target that prevalently expressed in multiple cancers with high unmet need, including ovarian and other gynecological cancers, while exhibiting minimal expression normal tissues. Due to FRa’s favorable profile, antibody-drug conjugates (ADCs) are being explored this setting. Here we present the preclinical characterization of new anti-FRa ADC, ZW191. ZW191 an antibody drug conjugate (ADC) comprised humanized...
<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>
Abstract Background: Glypican-3 (GPC3) is a cell-surface oncofetal glycoprotein frequently expressed in hepatocellular carcinoma (HCC) with minimal presence normal adult tissues. ZW251 an antibody-drug conjugate (ADC) targeting human GPC3, composed of humanized IgG1 antibody conjugated to novel camptothecin-based topoisomerase 1 inhibitor, ZD06519, via maleimide anchor and glycyl phenylalanyl glycine (GGFG)-aminomethyl (AM) cleavable linker. Materials Methods: Extensive functional...
Abstract Background: NaPi2b is a multi-pass transmembrane sodium-dependent phosphate transport protein encoded by the gene SLC34A2. involved in normal homeostasis and its expression found lung, liver, small intestine. highly expressed ovarian carcinomas, lung adenocarcinomas, colorectal carcinomas. ZW220 an antibody-drug conjugate (ADC) targeting human NaPi2b, wherein humanized IgG1 antibody conjugated to novel camptothecin-based topoisomerase I inhibitor, ZD06519. The drug linker comprised...