{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T18:03:03Z","timestamp":1762452183082,"version":"build-2065373602"},"reference-count":57,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T00:00:00Z","timestamp":1756857600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T00:00:00Z","timestamp":1756857600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"name":"Madurai Kamaraj University- Rashtriya Uchchatar Shiksha Abhiyan","award":["007-R2\/MKU\/SOC\/2020-2021"],"award-info":[{"award-number":["007-R2\/MKU\/SOC\/2020-2021"]}]},{"DOI":"10.13039\/501100008762","name":"Tamil Nadu State Council for Higher Education","doi-asserted-by":"crossref","award":["131\/2019A"],"award-info":[{"award-number":["131\/2019A"]}],"id":[{"id":"10.13039\/501100008762","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100018333","name":"Tamil Nadu State Council for Science and Technology","doi-asserted-by":"crossref","award":["TNSCST\/STP\/Covid-19\/2020-21-3682"],"award-info":[{"award-number":["TNSCST\/STP\/Covid-19\/2020-21-3682"]}],"id":[{"id":"10.13039\/100018333","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Department of Science and Technology-Fund for Improvement of S&T Infrastructure in Universities","award":["SR\/FST\/CS-II\/2017\/35(C)"],"award-info":[{"award-number":["SR\/FST\/CS-II\/2017\/35(C)"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Comput Aided Mol Des"],"published-print":{"date-parts":[[2025,12]]},"DOI":"10.1007\/s10822-025-00647-8","type":"journal-article","created":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T01:12:07Z","timestamp":1756861927000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Structure-based design of alicyclic fused pyrazole derivatives for targeting TGF-\u03b2 receptor I kinase: molecular docking and dynamics insights"],"prefix":"10.1007","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-1573-6300","authenticated-orcid":false,"given":"Natarajan","family":"Saravanakumar","sequence":"first","affiliation":[]},{"given":"Arunagiri Sivanesan","family":"Aruna Poorani","sequence":"additional","affiliation":[]},{"given":"Ganesapandian","family":"Latha","sequence":"additional","affiliation":[]},{"given":"Anantha Krishnan","family":"Dhanabalan","sequence":"additional","affiliation":[]},{"given":"Srimari","family":"Srikanth","sequence":"additional","affiliation":[]},{"given":"Venkatasubramanian","family":"Ulaganathan","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2827-8552","authenticated-orcid":false,"given":"Palaniswamy","family":"Suresh","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2025,9,3]]},"reference":[{"key":"647_CR1","doi-asserted-by":"publisher","first-page":"1794","DOI":"10.1021\/acs.jcim.4c00247","volume":"64","author":"Y Tang","year":"2024","unstructured":"Tang Y, Moretti R, Meiler J (2024) Recent advances in automated structure-based DE Novo drug design. J Chem Inf Model 64:1794\u20131805. https:\/\/doi.org\/10.1021\/acs.jcim.4c00247","journal-title":"J Chem Inf Model"},{"key":"647_CR2","doi-asserted-by":"publisher","first-page":"787","DOI":"10.1016\/j.chembiol.2003.09.002","volume":"10","author":"AC Anderson","year":"2003","unstructured":"Anderson AC (2003) The process of structure-based drug design. Chem Biol 10:787\u2013797. https:\/\/doi.org\/10.1016\/j.chembiol.2003.09.002","journal-title":"Chem Biol"},{"key":"647_CR3","doi-asserted-by":"publisher","first-page":"3143","DOI":"10.1021\/jm070129k","volume":"50","author":"D-K Kim","year":"2007","unstructured":"Kim D-K, Jang Y, Lee HS, Park H-J, Yoo J (2007) Synthesis and biological evaluation of 4(5)-(6-alkylpyridin-2-yl)imidazoles as transforming growth factor-beta type 1 receptor kinase inhibitors. J Med Chem 50:3143\u20133147. https:\/\/doi.org\/10.1021\/jm070129k","journal-title":"J Med Chem"},{"key":"647_CR4","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1159\/000327776","volume":"48","author":"Y Tang","year":"2011","unstructured":"Tang Y, Yang X, Friesel RE, Vary CPH, Liaw L (2011) Mechanisms of TGF-\u03b2-induced differentiation in human vascular smooth muscle cells. J Vasc Res 48:485\u2013494. https:\/\/doi.org\/10.1159\/000327776","journal-title":"J Vasc Res"},{"key":"647_CR5","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1111\/micc.12099","volume":"21","author":"L Jonker","year":"2014","unstructured":"Jonker L (2014) TGF-\u03b2 & BMP receptors endoglin and ALK1: overview of their functional role and status as antiangiogenic targets. Microcirculation 21:93\u2013103. https:\/\/doi.org\/10.1111\/micc.12099","journal-title":"Microcirculation"},{"key":"647_CR6","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1016\/s0092-8674(03)00432-x","volume":"113","author":"Y Shi","year":"2003","unstructured":"Shi Y, Massagu\u00e9 J (2003) Mechanisms of TGF-beta signaling from cell membrane to the nucleus. Cell 113:685\u2013700. https:\/\/doi.org\/10.1016\/s0092-8674(03)00432-x","journal-title":"Cell"},{"key":"647_CR7","doi-asserted-by":"publisher","first-page":"786728","DOI":"10.3389\/fcell.2021.786728","volume":"9","author":"M Zhang","year":"2021","unstructured":"Zhang M, Zhang YY, Chen Y, Wang J, Wang Q, Lu H (2021) TGF-\u03b2 signaling and resistance to cancer therapy. Front Cell Dev Biol 9:786728. https:\/\/doi.org\/10.3389\/fcell.2021.786728","journal-title":"Front Cell Dev Biol"},{"key":"647_CR8","doi-asserted-by":"publisher","first-page":"3099","DOI":"10.3390\/cancers12113099","volume":"12","author":"VW Xue","year":"2020","unstructured":"Xue VW, Chung JY-F, C\u00f3rdoba CAG, Cheung AH-K, Kang W, Lam EW-F, Leung K-T, To K-F, Lan H-Y, Tang PM-K (2020) Transforming growth factor-\u03b2: A multifunctional regulator of cancer immunity. Cancers (Basel) 12:3099. https:\/\/doi.org\/10.3390\/cancers12113099","journal-title":"Cancers (Basel)"},{"key":"647_CR9","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1016\/s0197-0186(01)00046-8","volume":"39","author":"E Masliah","year":"2001","unstructured":"Masliah E, Ho G, Wyss-Coray T (2001) Functional role of TGF beta in alzheimer\u2019s disease microvascular injury: lessons from Transgenic mice. Neurochem Int 39:393\u2013400. https:\/\/doi.org\/10.1016\/s0197-0186(01)00046-8","journal-title":"Neurochem Int"},{"key":"647_CR10","doi-asserted-by":"publisher","first-page":"1020","DOI":"10.1016\/j.autrev.2014.08.028","volume":"13","author":"Z Yan","year":"2014","unstructured":"Yan Z, Kui Z, Ping Z (2014) Reviews and prospectives of signaling pathway analysis in idiopathic pulmonary fibrosis. Autoimmun Rev 13:1020\u20131025. https:\/\/doi.org\/10.1016\/j.autrev.2014.08.028","journal-title":"Autoimmun Rev"},{"key":"647_CR11","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1016\/j.matbio.2018.04.006","volume":"68\u201369","author":"D Schuppan","year":"2018","unstructured":"Schuppan D, Ashfaq-Khan M, Yang AT, Kim YO (2018) Liver fibrosis: direct antifibrotic agents and targeted therapies. Matrix Biol 68\u201369:435\u2013451. https:\/\/doi.org\/10.1016\/j.matbio.2018.04.006","journal-title":"Matrix Biol"},{"key":"647_CR12","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1016\/j.canlet.2016.03.033","volume":"379","author":"LH Katz","year":"2016","unstructured":"Katz LH, Likhter M, Jogunoori W, Belkin M, Ohshiro K, Mishra L (2016) TGF-\u03b2 signaling in liver and Gastrointestinal cancers. Cancer Lett 379:166\u2013172. https:\/\/doi.org\/10.1016\/j.canlet.2016.03.033","journal-title":"Cancer Lett"},{"key":"647_CR13","doi-asserted-by":"publisher","first-page":"1010","DOI":"10.1016\/j.molmed.2019.06.007","volume":"25","author":"J Chen","year":"2019","unstructured":"Chen J, Gingold JA, Su X (2019) Immunomodulatory TGF-\u03b2 signaling in hepatocellular carcinoma. Trends Mol Med 25:1010\u20131023. https:\/\/doi.org\/10.1016\/j.molmed.2019.06.007","journal-title":"Trends Mol Med"},{"key":"647_CR14","doi-asserted-by":"publisher","first-page":"4479","DOI":"10.2147\/DDDT.S86621","volume":"9","author":"S Herbertz","year":"2015","unstructured":"Herbertz S, Sawyer JS, Stauber AJ, Gueorguieva I, Driscoll KE, Estrem ST, Cleverly AL, Desaiah D, Guba SC, Benhadji KA, Slapak CA, Lahn MM (2015) Clinical development of Galunisertib (LY2157299 monohydrate), a small molecule inhibitor of transforming growth factor-beta signaling pathway. Drug Des Devel Ther 9:4479\u20134499. https:\/\/doi.org\/10.2147\/DDDT.S86621","journal-title":"Drug Des Devel Ther"},{"key":"647_CR15","doi-asserted-by":"publisher","first-page":"737","DOI":"10.1158\/1535-7163.737.3.6","volume":"3","author":"MD Hjelmeland","year":"2004","unstructured":"Hjelmeland MD, Hjelmeland AB, Sathornsumetee S, Reese ED, Herbstreith MH, Laping NJ, Friedman HS, Bigner DD, Wang X-F, Rich JN (2004) SB-431542, a small molecule transforming growth factor-\u03b2-receptor antagonist, inhibits human glioma cell line proliferation and motility. Mol Cancer Ther 3:737\u2013745. https:\/\/doi.org\/10.1158\/1535-7163.737.3.6","journal-title":"Mol Cancer Ther"},{"key":"647_CR16","doi-asserted-by":"publisher","first-page":"744","DOI":"10.1124\/mol.65.3.744","volume":"65","author":"S DaCosta Byfield","year":"2004","unstructured":"DaCosta Byfield S, Major C, Laping NJ, Roberts AB (2004) SB-505124 is a selective inhibitor of transforming growth factor-beta type I receptors ALK4, ALK5, and ALK7. Mol Pharmacol 65:744\u2013752. https:\/\/doi.org\/10.1124\/mol.65.3.744","journal-title":"Mol Pharmacol"},{"key":"647_CR17","doi-asserted-by":"publisher","first-page":"7954","DOI":"10.1158\/0008-5472","volume":"64","author":"M Uhl","year":"2004","unstructured":"Uhl M, Aulwurm S, Wischhusen J, Weiler M, Ma JY, Almirez R, Mangadu R, Liu Y-W, Platten M, Herrlinger U, Murphy A, Wong DH, Wick W, Higgins LS, Weller M (2004) SD-208, a novel transforming growth factor beta receptor I kinase inhibitor, inhibits growth and invasiveness and enhances immunogenicity of murine and human glioma cells in vitro and in vivo. Cancer Res 64:7954\u20137961. https:\/\/doi.org\/10.1158\/0008-5472","journal-title":"Cancer Res"},{"key":"647_CR18","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1016\/j.ejphar.2014.03.045","volume":"734","author":"H Terashima","year":"2014","unstructured":"Terashima H, Kato M, Ebisawa M, Kobayashi H, Suzuki K, Nezu Y, Sada T (2014) R-268712, an orally active transforming growth factor-\u03b2 type I receptor inhibitor, prevents glomerular sclerosis in a Thy1 nephritis model. Eur J Pharmacol 734:60\u201366. https:\/\/doi.org\/10.1016\/j.ejphar.2014.03.045","journal-title":"Eur J Pharmacol"},{"key":"647_CR19","doi-asserted-by":"publisher","first-page":"112354","DOI":"10.1016\/j.ejmech.2020.112354","volume":"198","author":"G Xu","year":"2020","unstructured":"Xu G, Zhang Y, Wang H, Guo Z, Wang X, Li X, Chang S, Sun T, Yu Z, Xu T, Zhao L, Wang Y, Yu W (2020) Synthesis and biological evaluation of 4-(pyridin-4-oxy)-3-(3,3-difluorocyclobutyl)-pyrazole derivatives as novel potent transforming growth factor-\u03b2 type 1 receptor inhibitors. Eur J Med Chem 198:112354. https:\/\/doi.org\/10.1016\/j.ejmech.2020.112354","journal-title":"Eur J Med Chem"},{"key":"647_CR20","doi-asserted-by":"publisher","first-page":"2277","DOI":"10.1016\/j.bmcl.2009.02.087","volume":"19","author":"F Gellibert","year":"2009","unstructured":"Gellibert F, Fouchet M-H, Nguyen V-L, Wang R, Krysa G, de Gouville A-C, Huet S, Dodic N (2009) Design of novel Quinazoline derivatives and related analogues as potent and selective ALK5 inhibitors. Bioorg Med Chem Lett 19:2277\u20132281. https:\/\/doi.org\/10.1016\/j.bmcl.2009.02.087","journal-title":"Bioorg Med Chem Lett"},{"key":"647_CR21","doi-asserted-by":"publisher","first-page":"7901","DOI":"10.1021\/jm900807w","volume":"52","author":"FW Goldberg","year":"2009","unstructured":"Goldberg FW, Ward RA, Powell SJ, Debreczeni JE, Norman RA, Roberts NJ, Dishington AP, Gingell HJ, Wickson KF, Roberts AL (2009) Rapid generation of a high quality lead for transforming growth factor-beta (TGF-beta) type I receptor (ALK5). J Med Chem 52:7901\u20137905. https:\/\/doi.org\/10.1021\/jm900807w","journal-title":"J Med Chem"},{"key":"647_CR22","doi-asserted-by":"publisher","first-page":"4090","DOI":"10.3390\/ijms20174090","volume":"20","author":"J-H Jiang","year":"2019","unstructured":"Jiang J-H, Deng P (2019) Discovery of new inhibitors of transforming growth factor-beta type 1 receptor by utilizing Docking and structure-activity relationship analysis. Int J Mol Sci 20:4090. https:\/\/doi.org\/10.3390\/ijms20174090","journal-title":"Int J Mol Sci"},{"key":"647_CR23","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1016\/j.compbiolchem.2018.07.002","volume":"76","author":"W Li","year":"2018","unstructured":"Li W, Liu X, Muhammad S, Shi J, Meng Y, Wang J (2018) Computational investigation of TGF-\u03b2 receptor inhibitors for treatment of idiopathic pulmonary fibrosis: Field-based QSAR model and molecular dynamics simulation. Comput Biol Chem 76:139\u2013150. https:\/\/doi.org\/10.1016\/j.compbiolchem.2018.07.002","journal-title":"Comput Biol Chem"},{"key":"647_CR24","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1016\/j.compbiolchem.2018.07.011","volume":"76","author":"TV Ajay Kumar","year":"2018","unstructured":"Ajay Kumar TV, Athavan AAS, Loganathan C, Saravanan K, Kabilan S, Parthasarathy V (2018) Design, 3D QSAR modeling and Docking of TGF-\u03b2 type I inhibitors to target cancer. Comput Biol Chem 76:232\u2013244. https:\/\/doi.org\/10.1016\/j.compbiolchem.2018.07.011","journal-title":"Comput Biol Chem"},{"key":"647_CR25","doi-asserted-by":"publisher","first-page":"112042","DOI":"10.1016\/j.ejmech.2020.112042","volume":"189","author":"H Wu","year":"2020","unstructured":"Wu H, Sun Y, Wong WL, Cui J, Li J, You X, Yap LF, Huang Y, Hong W, Yang X, Paterson IC, Wang H (2020) The development of a novel transforming growth factor-\u03b2 (TGF-\u03b2) inhibitor that disrupts ligand-receptor interactions. Eur J Med Chem 189:112042. https:\/\/doi.org\/10.1016\/j.ejmech.2020.112042","journal-title":"Eur J Med Chem"},{"key":"647_CR26","doi-asserted-by":"publisher","first-page":"961","DOI":"10.1016\/j.ejmech.2017.08.023","volume":"139","author":"M Murahari","year":"2017","unstructured":"Murahari M, Prakash KV, Peters GJ, Mayur YC (2017) Acridone-pyrimidine hybrids- design, synthesis, cytotoxicity studies in resistant and sensitive cancer cells and molecular Docking studies. Eur J Med Chem 139:961\u2013981. https:\/\/doi.org\/10.1016\/j.ejmech.2017.08.023","journal-title":"Eur J Med Chem"},{"key":"647_CR27","unstructured":"Schr\u00f6dinger Release 2024-2: Induced Fit Docking protocol; Glide, Schr\u00f6dinger, LLC, New York, NY (2024) ; Prime, Schr\u00f6dinger, LLC, New York, NY, 2024"},{"key":"647_CR28","doi-asserted-by":"publisher","first-page":"e2100240","DOI":"10.1002\/minf.202100240","volume":"41","author":"K Sankar","year":"2022","unstructured":"Sankar K, Trainor K, Blazer LL, Adams JJ, Sidhu SS, Day T, Meiering E, Maier JKX (2022) A descriptor set for quantitative structure-property relationship prediction in biologics. Mol Inf 41:e2100240. https:\/\/doi.org\/10.1002\/minf.202100240","journal-title":"Mol Inf"},{"key":"647_CR29","doi-asserted-by":"publisher","first-page":"3581","DOI":"10.1016\/j.bmcl.2004.04.007","volume":"14","author":"JS Sawyer","year":"2004","unstructured":"Sawyer JS, Beight DW, Britt KS, Anderson BD, Campbell RM, Goodson T, Herron DK, Li H-Y, McMillen WT, Mort N, Parsons S, Smith ECR, Wagner JR, Yan L, Zhang F, Yingling JM (2004) Synthesis and activity of new aryl- and heteroaryl-substituted 5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole inhibitors of the transforming growth factor-\u03b2 type I receptor kinase domain. Bioorg Med Chem Lett 14:3581\u20133584. https:\/\/doi.org\/10.1016\/j.bmcl.2004.04.007","journal-title":"Bioorg Med Chem Lett"},{"key":"647_CR30","volume-title":"Protein Preparation workflow; epik, schr\u00f6dinger","author":"Schr\u00f6dinger Release 2024-2","year":"2024","unstructured":"Schr\u00f6dinger Release 2024-2 (2024) Protein Preparation workflow; epik, schr\u00f6dinger. LLC, New York, NY"},{"key":"647_CR31","unstructured":"OPLS4 Improving Force Field Accuracy on Challenging Regimes of Chemical Space - PubMed. https:\/\/pubmed.ncbi.nlm.nih.gov\/34096718\/"},{"key":"647_CR32","doi-asserted-by":"publisher","unstructured":"Bowers, K. J., Chow, D. E., Xu, H., Dror, R. O., Eastwood, M. P., Gregersen, B. A.,\u2026 Shaw, D. E. (2006). Scalable Algorithms for Molecular Dynamics Simulations on Commodity Clusters. In ACM\/IEEE SC 2006 Conference (SC\u201906) (pp. 43\u201343). IEEE. https:\/\/doi.org\/10.1109\/SC.2006.54","DOI":"10.1109\/SC.2006.54"},{"key":"647_CR33","doi-asserted-by":"publisher","unstructured":"Banks, J. L., Beard, H. S., Cao, Y., Cho, A. E., Damm, W., Farid, R., \u2026 Levy, R. M.(2005). Integrated Modeling Program, Applied Chemical Theory (IMPACT). Journal of Computational Chemistry, 26(16), 1752\u20131780. https:\/\/doi.org\/10.1002\/jcc.20292","DOI":"10.1002\/jcc.20292"},{"issue":"1","key":"647_CR34","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1002\/wcms.3","volume":"1","author":"P Larsson","year":"2011","unstructured":"Larsson P, Hess B, Lindahl E (2011) Algorithm improvements for molecular dynamics simulations. WIREs Comput Mol Sci 1(1):93\u2013108. https:\/\/doi.org\/10.1002\/wcms.3","journal-title":"WIREs Comput Mol Sci"},{"issue":"8","key":"647_CR35","doi-asserted-by":"publisher","first-page":"4069","DOI":"10.1063\/1.449071","volume":"83","author":"DJ Evans","year":"1985","unstructured":"Evans DJ, Holian BL (1985) The Nose\u2013Hoover thermostat. J Chem Phys 83(8):4069\u20134074. https:\/\/doi.org\/10.1063\/1.449071","journal-title":"J Chem Phys"},{"issue":"5","key":"647_CR36","doi-asserted-by":"publisher","first-page":"4177","DOI":"10.1063\/1.467468","volume":"101","author":"GJ Martyna","year":"1994","unstructured":"Martyna GJ, Tobias DJ, Klein ML (1994) Constant pressure molecular dynamics algorithms. J Chem Phys 101(5):4177\u20134189. https:\/\/doi.org\/10.1063\/1.467468","journal-title":"J Chem Phys"},{"key":"647_CR37","doi-asserted-by":"publisher","first-page":"1147","DOI":"10.1002\/prot.25594","volume":"86","author":"K Sankar","year":"2018","unstructured":"Sankar K, Krystek SR Jr, Carl SM, Day T, Maier JKX (2018) AggScore: prediction of aggregation-prone regions in proteins based on the distribution of surface patches. Proteins 86:1147\u20131156. https:\/\/doi.org\/10.1002\/prot.25594","journal-title":"Proteins"},{"key":"647_CR38","doi-asserted-by":"publisher","first-page":"1451","DOI":"10.1021\/cr9903205","volume":"101","author":"FD Proft","year":"2001","unstructured":"Proft FD, Geerlings P (2001) Chem Rev 101:1451\u20131464. https:\/\/doi.org\/10.1021\/cr9903205","journal-title":"Chem Rev"},{"key":"647_CR39","unstructured":"Frisch A (2009) gaussian 09\u00a0W Reference, Wallingford, USA, 25, 470"},{"key":"647_CR40","unstructured":"Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, Scalmani G, Barone V, Mennucci B, Petersson GA, Nakatsuji H Gaussian 09, Revision D. 01, Gaussian, Inc https:\/\/gaussian.com\/g09citation\/"},{"key":"647_CR41","doi-asserted-by":"publisher","first-page":"3953","DOI":"10.1021\/jm0205705","volume":"46","author":"JS Sawyer","year":"2003","unstructured":"Sawyer JS, Anderson BD, Beight DW, Campbell RM, Jones ML, Herron DK, Lampe JW, McCowan JR, McMillen WT, Mort N, Parsons S, Smith ECR, Vieth M, Weir LC, Yan L, Zhang F, Yingling JM (2003) Synthesis and activity of new aryl- and heteroaryl-substituted pyrazole inhibitors of the transforming growth factor-beta type I receptor kinase domain. J Med Chem 46:3953\u20133956. https:\/\/doi.org\/10.1021\/jm0205705","journal-title":"J Med Chem"},{"key":"647_CR42","doi-asserted-by":"publisher","first-page":"4355","DOI":"10.1016\/j.bmcl.2003.09.028","volume":"13","author":"J Singh","year":"2003","unstructured":"Singh J, Chuaqui CE, Boriack-Sjodin PA, Lee W-C, Pontz T, Corbley MJ, Cheung H-K, Arduini RM, Mead JN, Newman MN, Papadatos JL, Bowes S, Josiah S, Ling LE (2003) Successful shape-Based virtual screening: the discovery of a potent inhibitor of the type I TGF\u03b2 receptor kinase (T\u03b2RI). Bioorg Med Chem Lett 13:4355\u20134359. https:\/\/doi.org\/10.1016\/j.bmcl.2003.09.028","journal-title":"Bioorg Med Chem Lett"},{"key":"647_CR43","doi-asserted-by":"publisher","first-page":"2302","DOI":"10.1021\/jm701199p","volume":"51","author":"H-Y Li","year":"2008","unstructured":"Li H-Y, McMillen WT, Heap CR, McCann DJ, Yan L, Campbell RM, Mundla SR, King C-HR, Dierks EA, Anderson BD, Britt KS, Huss KL, Voss MD, Wang Y, Clawson DK, Yingling JM, Sawyer JS (2008) Optimization of a Dihydropyrrolopyrazole series of transforming growth factor-beta type I receptor kinase domain inhibitors: discovery of an orally bioavailable transforming growth factor-beta receptor type I inhibitor as antitumor agent. J Med Chem 51:2302\u20132306. https:\/\/doi.org\/10.1021\/jm701199p","journal-title":"J Med Chem"},{"key":"647_CR44","doi-asserted-by":"publisher","first-page":"6617","DOI":"10.1021\/jo049274l","volume":"69","author":"AR Katritzky","year":"2004","unstructured":"Katritzky AR, Wang Z, Wang M, Wilkerson CR, Hall CD, Akhmedov NG (2004) Preparation of beta-keto esters and beta-diketones by C-acylation\/deacetylation of acetoacetic esters and acetonyl ketones with 1-acylbenzotriazoles. J Org Chem 69:6617\u20136622. https:\/\/doi.org\/10.1021\/jo049274l","journal-title":"J Org Chem"},{"key":"647_CR45","unstructured":"Xiangyu F, Zhaozhong D, Lihong H, Shuhui C (2020) Double Pyrazole Compound as TGF-\u03b2R1 Kinase Inhibitor, 2020088526:A1"},{"key":"647_CR46","unstructured":"Hick A, Gobert B, Riguet E (2021) Polyaromatic urea derivatives and their use in the treatment of muscle diseases, 2021013712:A1"},{"key":"647_CR47","doi-asserted-by":"publisher","first-page":"3860","DOI":"10.1039\/c8sc01016a","volume":"9","author":"JM Quibell","year":"2018","unstructured":"Quibell JM, Perry GJP, Cannas DM, Larrosa I (2018) Transition-metal-free decarboxylative bromination of aromatic carboxylic acids. Chem Sci 9:3860\u20133865. https:\/\/doi.org\/10.1039\/c8sc01016a","journal-title":"Chem Sci"},{"key":"647_CR48","doi-asserted-by":"publisher","first-page":"6001","DOI":"10.1016\/j.tetlet.2014.09.040","volume":"55","author":"K Harada","year":"2014","unstructured":"Harada K, Arioka C, Miyakita A, Kubo M, Fukuyama Y (2014) Efficient synthesis of neurotrophic Honokiol using Suzuki\u2013Miyaura reactions. Tetrahedron Lett 55:6001\u20136003. https:\/\/doi.org\/10.1016\/j.tetlet.2014.09.040","journal-title":"Tetrahedron Lett"},{"key":"647_CR49","doi-asserted-by":"publisher","first-page":"113763","DOI":"10.1016\/j.ejmech.2021.113763","volume":"225","author":"A Kharbanda","year":"2021","unstructured":"Kharbanda A, Tran P, Zhang L, Leung Y-K, Li H-Y, Frett B (2021) Discovery of 4-aminoquinolines as highly selective TGF\u03b2R1 inhibitors with an attenuated MAP4K4 profile for potential applications in immuno-oncology. Eur J Med Chem 225:113763. https:\/\/doi.org\/10.1016\/j.ejmech.2021.113763","journal-title":"Eur J Med Chem"},{"key":"647_CR50","doi-asserted-by":"publisher","first-page":"4846","DOI":"10.1021\/acs.orglett.5b02413","volume":"17","author":"AS Henderson","year":"2015","unstructured":"Henderson AS, Medina S, Bower JF, Galan MC (2015) Nucleophilic aromatic substitution (SNAr) as an approach to challenging carbohydrate-aryl ethers. Org Lett 17:4846\u20134849. https:\/\/doi.org\/10.1021\/acs.orglett.5b02413","journal-title":"Org Lett"},{"key":"647_CR51","doi-asserted-by":"publisher","first-page":"951","DOI":"10.1016\/j.molstruc.2018.07.079","volume":"1173","author":"S Suresh Kumar","year":"2018","unstructured":"Suresh Kumar S, Athimoolam S, Sridhar B (2018) Structural, spectral, theoretical and anticancer studies on new co-crystal of the drug 5-fluorouracil. J Mol Struct 1173:951\u2013958. https:\/\/doi.org\/10.1016\/j.molstruc.2018.07.079","journal-title":"J Mol Struct"},{"key":"647_CR52","doi-asserted-by":"publisher","first-page":"107894","DOI":"10.1016\/j.carres.2019.107894","volume":"487","author":"AI Khodair","year":"2020","unstructured":"Khodair AI, Awad MK, Gesson J-P, Elshaier YAMM (2020) New N-ribosides and N-mannosides of Rhodanine derivatives with anticancer activity on leukemia cell line: design, synthesis, DFT and molecular modelling studies. Carbohydr Res 487:107894. https:\/\/doi.org\/10.1016\/j.carres.2019.107894","journal-title":"Carbohydr Res"},{"key":"647_CR53","unstructured":"https:\/\/www.growingscience.com\/ccl\/Vol14\/ccl_2024_45.pdf"},{"key":"647_CR54","doi-asserted-by":"publisher","unstructured":"Obakachi VA, Nchiozem-Ngnitedem V-A, Govender KK, Govender PP (2025) In Silico exploration of natural Xanthone derivatives as potential inhibitors of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication and cellular entry. J Comput Aided Mol Des 39. https:\/\/doi.org\/10.1007\/s10822-025-00585-5","DOI":"10.1007\/s10822-025-00585-5"},{"key":"647_CR55","doi-asserted-by":"publisher","first-page":"105325","DOI":"10.1016\/j.bioorg.2021.105325","volume":"116","author":"FF Sherbiny","year":"2021","unstructured":"Sherbiny FF, Bayoumi AH, El-Morsy AM, Sobhy M, Hagras M (2021) Design, synthesis, biological evaluation, and molecular Docking studies of novel Pyrazolo[3,4-d]Pyrimidine derivative scaffolds as potent EGFR inhibitors and cell apoptosis inducers. Bioorg Chem 116:105325. https:\/\/doi.org\/10.1016\/j.bioorg.2021.105325","journal-title":"Bioorg Chem"},{"key":"647_CR56","doi-asserted-by":"publisher","first-page":"1117","DOI":"10.1002\/cmdc.201600182","volume":"11","author":"A Daina","year":"2016","unstructured":"Daina A, Zoete V (2016) A BOILED-Egg to predict Gastrointestinal absorption and brain penetration of small molecules. ChemMedChem 11:1117\u20131121. https:\/\/doi.org\/10.1002\/cmdc.201600182","journal-title":"ChemMedChem"},{"key":"647_CR57","doi-asserted-by":"publisher","first-page":"e0166061","DOI":"10.1371\/journal.pone.0166061","volume":"12","author":"M Aryal","year":"2017","unstructured":"Aryal M, Fischer K, Gentile C, Gitto S, Zhang Y-Z, McDannold N (2017) Effects on P-Glycoprotein expression after Blood-Brain barrier disruption using focused ultrasound and microbubbles. PLoS ONE 12:e0166061. https:\/\/doi.org\/10.1371\/journal.pone.0166061","journal-title":"PLoS ONE"}],"container-title":["Journal of Computer-Aided Molecular Design"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10822-025-00647-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10822-025-00647-8\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10822-025-00647-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T17:56:49Z","timestamp":1762451809000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10822-025-00647-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,3]]},"references-count":57,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["647"],"URL":"https:\/\/doi.org\/10.1007\/s10822-025-00647-8","relation":{},"ISSN":["0920-654X","1573-4951"],"issn-type":[{"type":"print","value":"0920-654X"},{"type":"electronic","value":"1573-4951"}],"subject":[],"published":{"date-parts":[[2025,9,3]]},"assertion":[{"value":"12 May 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 August 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 September 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"73"}}