GW-788,388

GW-788,388
Identifiers
	IUPAC name 4-(4-(3-(Pyridin-2-yl)-1H-pyrazol-4-yl)pyridin-2-yl)-N-(tetrahydro-2H-pyran-4-yl)benzamide;
CAS Number	452342-67-5;
PubChem CID	10202642;
Chemical and physical data
Formula	C25H23N5O2
Molar mass	425.492 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES C1COCCC1NC(=O)C2=CC=C(C=C2)C3=NC=CC(=C3)C4=C(NN=C4)C5=CC=CC=N5;
	InChI InChI=1S/C25H23N5O2/c31-25(29-20-9-13-32-14-10-20)18-6-4-17(5-7-18)23-15-19(8-12-27-23)21-16-28-30-24(21)22-3-1-2-11-26-22/h1-8,11-12,15-16,20H,9-10,13-14H2,(H,28,30)(H,29,31); Key:SAGZIBJAQGBRQA-UHFFFAOYSA-N;

GW 788388 is a synthetic compound which acts as a potent and selective inhibitor for TGF beta receptor 1.^[1] It has applications in research into various disorders such as liver, kidney and heart disease (especially associated with Chagas disease),^[2]^[3]^[4]^[5]^[6] and potential antiviral properties.^[7]

References

^ Gellibert F, de Gouville AC, Woolven J, Mathews N, Nguyen VL, Bertho-Ruault C, et al. (April 2006). "Discovery of 4-{4-[3-(pyridin-2-yl)-1H-pyrazol-4-yl]pyridin-2-yl}-N-(tetrahydro-2H- pyran-4-yl)benzamide (GW788388): a potent, selective, and orally active transforming growth factor-beta type I receptor inhibitor". Journal of Medicinal Chemistry. 49 (7): 2210–2221. doi:10.1021/jm0509905. PMID 16570917.
^ McMillin M, Grant S, Frampton G, Petrescu AD, Williams E, Jefferson B, DeMorrow S (May 2019). "The TGFβ1 Receptor Antagonist GW788388 Reduces JNK Activation and Protects Against Acetaminophen Hepatotoxicity in Mice". Toxicological Sciences. 170 (2): 549–561. doi:10.1093/toxsci/kfz122. PMC 6821297. PMID 31132129.
^ Petersen M, Thorikay M, Deckers M, van Dinther M, Grygielko ET, Gellibert F, et al. (March 2008). "Oral administration of GW788388, an inhibitor of TGF-beta type I and II receptor kinases, decreases renal fibrosis". Kidney International. 73 (6): 705–715. doi:10.1038/sj.ki.5002717. PMID 18075500.
^ Tan SM, Zhang Y, Connelly KA, Gilbert RE, Kelly DJ (May 2010). "Targeted inhibition of activin receptor-like kinase 5 signaling attenuates cardiac dysfunction following myocardial infarction". American Journal of Physiology. Heart and Circulatory Physiology. 298 (5): H1415–H1425. doi:10.1152/ajpheart.01048.2009. PMID 20154262.
^ Ferreira RR, Abreu RD, Vilar-Pereira G, Degrave W, Meuser-Batista M, Ferreira NV, et al. (July 2019). "TGF-β inhibitor therapy decreases fibrosis and stimulates cardiac improvement in a pre-clinical study of chronic Chagas' heart disease". PLOS Neglected Tropical Diseases. 13 (7): e0007602. doi:10.1371/journal.pntd.0007602. PMC 6690554. PMID 31365537.
^ Lho Y, Do JY, Heo JY, Kim AY, Kim SW, Kang SH (April 2021). "Effects of TGF-β1 Receptor Inhibitor GW788388 on the Epithelial to Mesenchymal Transition of Peritoneal Mesothelial Cells". International Journal of Molecular Sciences. 22 (9): 4739. doi:10.3390/ijms22094739. PMC 8124410. PMID 33947038.
^ Teixeira GS, Andrade AA, Torres LR, Couto-Lima D, Moreira OC, Abreu R, et al. (September 2022). "Suppression of TGF-β/Smad2 signaling by GW788388 enhances DENV-2 clearance in macrophages". Journal of Medical Virology. 94 (9): 4359–4368. doi:10.1002/jmv.27879. PMC 9544077. PMID 35596058. S2CID 250497172.

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[1] Gellibert F, de Gouville AC, Woolven J, Mathews N, Nguyen VL, Bertho-Ruault C, et al. (April 2006). "Discovery of 4-{4-[3-(pyridin-2-yl)-1H-pyrazol-4-yl]pyridin-2-yl}-N-(tetrahydro-2H- pyran-4-yl)benzamide (GW788388): a potent, selective, and orally active transforming growth factor-beta type I receptor inhibitor". Journal of Medicinal Chemistry. 49 (7): 2210–2221. doi:10.1021/jm0509905. PMID 16570917.

[2] McMillin M, Grant S, Frampton G, Petrescu AD, Williams E, Jefferson B, DeMorrow S (May 2019). "The TGFβ1 Receptor Antagonist GW788388 Reduces JNK Activation and Protects Against Acetaminophen Hepatotoxicity in Mice". Toxicological Sciences. 170 (2): 549–561. doi:10.1093/toxsci/kfz122. PMC 6821297. PMID 31132129.

[3] Petersen M, Thorikay M, Deckers M, van Dinther M, Grygielko ET, Gellibert F, et al. (March 2008). "Oral administration of GW788388, an inhibitor of TGF-beta type I and II receptor kinases, decreases renal fibrosis". Kidney International. 73 (6): 705–715. doi:10.1038/sj.ki.5002717. PMID 18075500.

[4] Tan SM, Zhang Y, Connelly KA, Gilbert RE, Kelly DJ (May 2010). "Targeted inhibition of activin receptor-like kinase 5 signaling attenuates cardiac dysfunction following myocardial infarction". American Journal of Physiology. Heart and Circulatory Physiology. 298 (5): H1415–H1425. doi:10.1152/ajpheart.01048.2009. PMID 20154262.

[5] Ferreira RR, Abreu RD, Vilar-Pereira G, Degrave W, Meuser-Batista M, Ferreira NV, et al. (July 2019). "TGF-β inhibitor therapy decreases fibrosis and stimulates cardiac improvement in a pre-clinical study of chronic Chagas' heart disease". PLOS Neglected Tropical Diseases. 13 (7): e0007602. doi:10.1371/journal.pntd.0007602. PMC 6690554. PMID 31365537.

[6] Lho Y, Do JY, Heo JY, Kim AY, Kim SW, Kang SH (April 2021). "Effects of TGF-β1 Receptor Inhibitor GW788388 on the Epithelial to Mesenchymal Transition of Peritoneal Mesothelial Cells". International Journal of Molecular Sciences. 22 (9): 4739. doi:10.3390/ijms22094739. PMC 8124410. PMID 33947038.

[7] Teixeira GS, Andrade AA, Torres LR, Couto-Lima D, Moreira OC, Abreu R, et al. (September 2022). "Suppression of TGF-β/Smad2 signaling by GW788388 enhances DENV-2 clearance in macrophages". Journal of Medical Virology. 94 (9): 4359–4368. doi:10.1002/jmv.27879. PMC 9544077. PMID 35596058. S2CID 250497172.

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See also

References