Stanislaw Pikul
- Immune cells in cancer
- Cancer Research and Treatments
- Adenosine and Purinergic Signaling
- Receptor Mechanisms and Signaling
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Nanoplatforms for cancer theranostics
- Monoclonal and Polyclonal Antibodies Research
- Amino Acid Enzymes and Metabolism
- Click Chemistry and Applications
- Cell Adhesion Molecules Research
- S100 Proteins and Annexins
- Inflammatory mediators and NSAID effects
- Cancer-related gene regulation
Pharmacologic inhibition of the controlling immunity pathway enzymes arginases 1 and 2 (ARG1 ARG2) is a promising strategy for cancer immunotherapy. Here, we report discovery development OATD-02, an orally bioavailable, potent inhibitor. The unique pharmacologic properties OATD-02 are evidenced by targeting intracellular ARG1 ARG2, as well long drug-target residence time, moderate to high volume distribution, low clearance, which may jointly provide weapon against arginase-related tumor...
<p>Simulated human plasma concentration time profiles of OATD-02</p>
<p>PK and PD effects after intravenous administration of OATD-02 CB-1158 in Sprague-Dawley rats</p>
<p>The immunosuppressive character of ARG1 and ARG2 in the tumor microenvironment (TME)</p>
<p>Simulated human plasma concentration time profiles of OATD-02</p>
<p>Supplementary Figures 2 - 14 (Synthesis schemes).</p>
<p>Supplementary Materials and Methods not included in the main manuscript</p>
<p>Allometric scaling of human volume distribution (V-SAfu)</p>
<p>Analysis of B16F10 tumor growth in mice treated with OATD-02 all individuals subjected to the study.</p>
<p>Individual body weight changes in animals treated with OATD-02</p>
<p>Crystal structure of OATD-02 bound to hARG1</p>
<div>Abstract<p>Pharmacological inhibition of the controlling immunity pathway enzymes arginases 1 and 2 (ARG1 ARG2) is a promising strategy for cancer immunotherapy. Here, we report discovery development OATD-02, an orally bioavailable, potent inhibitor. The unique pharmacological properties OATD-02 are evidenced by targeting intracellular ARG1 ARG2, as well long drug-target residence time, moderate to high volume distribution, low clearance which may jointly provide weapon...
<p>Supplementary Materials and Methods not included in the main manuscript</p>
<p>Supplementary Figures 2 - 14 (Synthesis schemes).</p>
<p>Allometric scaling of human plasma clearance (CL-ROE)</p>
<p>Allometric scaling of human plasma clearance (CL-NAS)</p>
<p>Simulated human plasma concentration time profiles of OATD-02</p>
<p>Crystal structure of OATD-02 bound to hARG1</p>
<p>Analysis of B16F10 tumor growth in mice treated with OATD-02 all individuals subjected to the study.</p>
<p>PK and PD effects after intravenous administration of OATD-02 CB-1158 in Sprague-Dawley rats</p>
<p>Individual body weight changes in animals treated with OATD-02</p>
<p>The immunosuppressive character of ARG1 and ARG2 in the tumor microenvironment (TME)</p>
<p>Simulated human plasma concentration time profiles of OATD-02</p>
<p>Allometric scaling of human volume distribution (V-SAfu)</p>