Computational Screening and Experimental Validation on Multicomponent Crystals of a New Class of Janus Kinase (JAK) Inhibitor Drug with Improved Solubility
Developing multicomponent crystal forms, especially cocrystals and salts, is becoming a promising pathway to improve the solubility and bioavailability of drugs. Herein, new multicomponent crystals of SHR0302, a new generation of Janus Kinase (JAK) inhibitor that suffers from poor solubility, were d...
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| Format: | Article |
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MDPI AG
2022-11-01
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| Series: | Crystals |
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| Online Access: | https://www.mdpi.com/2073-4352/12/12/1722 |
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| author | Yujiang Xie Genpei Shi Jie Sun Si Li Wei Gao Yimin Hu Chang Zu Weiwei Tang Junbo Gong |
| author_facet | Yujiang Xie Genpei Shi Jie Sun Si Li Wei Gao Yimin Hu Chang Zu Weiwei Tang Junbo Gong |
| author_sort | Yujiang Xie |
| collection | DOAJ |
| description | Developing multicomponent crystal forms, especially cocrystals and salts, is becoming a promising pathway to improve the solubility and bioavailability of drugs. Herein, new multicomponent crystals of SHR0302, a new generation of Janus Kinase (JAK) inhibitor that suffers from poor solubility, were developed based on a cooperative approach of computational and experimental coformer screenings. Virtual screening methods, including the conductor-like screening model for realistic solvents (COSMO-RS) and molecular complementary (MC) analysis, were employed to predict the binding affinity between SHR0302 and selected coformers. The developed screening method was capable of reducing the screening database to 30 coformers from a total of 42 proposed coformers. The proof-of-concept experimental screening study was performed to demonstrate the efficiency of computational screening, wherein three new multicomponent crystalline forms were found and fully characterized by powder X-ray diffraction, thermal analysis, and IR and <sup>1</sup>H-NMR spectroscopy. Further, the measurements of the solubility property of these new multicomponent crystal forms reveal an apparent promotion compared with the drug alone. Finally, the receiver operator characteristic (ROC) curve was used to assess the prediction performance of the COSMO-RS model. It was found that the established screening model can effectively shorten the experimental screening time and efforts. |
| first_indexed | 2024-03-09T17:10:03Z |
| format | Article |
| id | doaj.art-1e2b057e93bc4c65b2b479d51294e8f0 |
| institution | Directory Open Access Journal |
| issn | 2073-4352 |
| language | English |
| last_indexed | 2024-03-09T17:10:03Z |
| publishDate | 2022-11-01 |
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| record_format | Article |
| series | Crystals |
| spelling | doaj.art-1e2b057e93bc4c65b2b479d51294e8f02023-11-24T14:09:50ZengMDPI AGCrystals2073-43522022-11-011212172210.3390/cryst12121722Computational Screening and Experimental Validation on Multicomponent Crystals of a New Class of Janus Kinase (JAK) Inhibitor Drug with Improved SolubilityYujiang Xie0Genpei Shi1Jie Sun2Si Li3Wei Gao4Yimin Hu5Chang Zu6Weiwei Tang7Junbo Gong8School of Chemical Engineering and Technology, State Key Laboratory of Chemical Engineering, The Co-Innovation Center of Chemistry and Chemical Engineering of Tianjin, Tianjin University, Tianjin 300072, ChinaSchool of Chemical Engineering and Technology, State Key Laboratory of Chemical Engineering, The Co-Innovation Center of Chemistry and Chemical Engineering of Tianjin, Tianjin University, Tianjin 300072, ChinaSchool of Chemical Engineering and Technology, State Key Laboratory of Chemical Engineering, The Co-Innovation Center of Chemistry and Chemical Engineering of Tianjin, Tianjin University, Tianjin 300072, ChinaSchool of Chemical Engineering and Technology, State Key Laboratory of Chemical Engineering, The Co-Innovation Center of Chemistry and Chemical Engineering of Tianjin, Tianjin University, Tianjin 300072, ChinaJiangsu Hengrui Pharmaceuticals Co., Ltd., Lianyungang 222000, ChinaJiangsu Hengrui Pharmaceuticals Co., Ltd., Lianyungang 222000, ChinaJiangsu Hengrui Pharmaceuticals Co., Ltd., Lianyungang 222000, ChinaSchool of Chemical Engineering and Technology, State Key Laboratory of Chemical Engineering, The Co-Innovation Center of Chemistry and Chemical Engineering of Tianjin, Tianjin University, Tianjin 300072, ChinaSchool of Chemical Engineering and Technology, State Key Laboratory of Chemical Engineering, The Co-Innovation Center of Chemistry and Chemical Engineering of Tianjin, Tianjin University, Tianjin 300072, ChinaDeveloping multicomponent crystal forms, especially cocrystals and salts, is becoming a promising pathway to improve the solubility and bioavailability of drugs. Herein, new multicomponent crystals of SHR0302, a new generation of Janus Kinase (JAK) inhibitor that suffers from poor solubility, were developed based on a cooperative approach of computational and experimental coformer screenings. Virtual screening methods, including the conductor-like screening model for realistic solvents (COSMO-RS) and molecular complementary (MC) analysis, were employed to predict the binding affinity between SHR0302 and selected coformers. The developed screening method was capable of reducing the screening database to 30 coformers from a total of 42 proposed coformers. The proof-of-concept experimental screening study was performed to demonstrate the efficiency of computational screening, wherein three new multicomponent crystalline forms were found and fully characterized by powder X-ray diffraction, thermal analysis, and IR and <sup>1</sup>H-NMR spectroscopy. Further, the measurements of the solubility property of these new multicomponent crystal forms reveal an apparent promotion compared with the drug alone. Finally, the receiver operator characteristic (ROC) curve was used to assess the prediction performance of the COSMO-RS model. It was found that the established screening model can effectively shorten the experimental screening time and efforts.https://www.mdpi.com/2073-4352/12/12/1722multicomponent crystalscocrystalsCOSMO-RScocrystal predictionsolubility enhancement |
| spellingShingle | Yujiang Xie Genpei Shi Jie Sun Si Li Wei Gao Yimin Hu Chang Zu Weiwei Tang Junbo Gong Computational Screening and Experimental Validation on Multicomponent Crystals of a New Class of Janus Kinase (JAK) Inhibitor Drug with Improved Solubility Crystals multicomponent crystals cocrystals COSMO-RS cocrystal prediction solubility enhancement |
| title | Computational Screening and Experimental Validation on Multicomponent Crystals of a New Class of Janus Kinase (JAK) Inhibitor Drug with Improved Solubility |
| title_full | Computational Screening and Experimental Validation on Multicomponent Crystals of a New Class of Janus Kinase (JAK) Inhibitor Drug with Improved Solubility |
| title_fullStr | Computational Screening and Experimental Validation on Multicomponent Crystals of a New Class of Janus Kinase (JAK) Inhibitor Drug with Improved Solubility |
| title_full_unstemmed | Computational Screening and Experimental Validation on Multicomponent Crystals of a New Class of Janus Kinase (JAK) Inhibitor Drug with Improved Solubility |
| title_short | Computational Screening and Experimental Validation on Multicomponent Crystals of a New Class of Janus Kinase (JAK) Inhibitor Drug with Improved Solubility |
| title_sort | computational screening and experimental validation on multicomponent crystals of a new class of janus kinase jak inhibitor drug with improved solubility |
| topic | multicomponent crystals cocrystals COSMO-RS cocrystal prediction solubility enhancement |
| url | https://www.mdpi.com/2073-4352/12/12/1722 |
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