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. 2021 Oct 18;12:6055. doi: 10.1038/s41467-021-26239-2

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© The Author(s) 2021

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 5 — A Chemical structure of conversion of prodrug PF-07304814 to the active moiety PF-00835231 by alkaline phosphatase. B Dose feasibility matrix illustrating the ability to achieve higher target exposures with increasing solubility and the limitations of dosing PF-00835231. with dosing either aqueous PF-00835231, clinically formulated PF-00835231, or aqueous PF-07304814 (prodrug). The infeasible limit (red) is assumed to be 1 L per day with a 2x potential benefit with a Cyp inhibitor (orange). Any dose under that is considered feasible (green).