SD36

SD36
Identifiers
  • [[2-[[(5S,8S,10aR)-8-[[(2S)-5-amino-1-(benzhydrylamino)-1,5-dioxopentan-2-yl]carbamoyl]-3-[8-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-3H-isoindol-4-yl]oct-7-ynoyl]-6-oxo-1,2,4,5,8,9,10,10a-octahydropyrrolo[1,2-a][1,5]diazocin-5-yl]carbamoyl]-1H-indol-5-yl]-difluoromethyl]phosphonic acid
CAS Number
PubChem CID
ChemSpider
ChEMBL
Chemical and physical data
FormulaC59H62F2N9O12P
Molar mass1158.167 g·mol−1
3D model (JSmol)
  • C1C[C@H](N2[C@H]1CCN(C[C@@H](C2=O)NC(=O)C3=CC4=C(N3)C=CC(=C4)C(F)(F)P(=O)(O)O)C(=O)CCCCCC#CC5=C6CN(C(=O)C6=CC=C5)C7CCC(=O)NC7=O)C(=O)N[C@@H](CCC(=O)N)C(=O)NC(C8=CC=CC=C8)C9=CC=CC=C9
  • InChI=1S/C59H62F2N9O12P/c60-59(61,83(80,81)82)39-21-23-43-38(31-39)32-45(63-43)54(75)65-46-34-68(51(73)20-11-3-1-2-6-13-35-18-12-19-41-42(35)33-69(57(41)78)47-26-28-50(72)66-55(47)76)30-29-40-22-25-48(70(40)58(46)79)56(77)64-44(24-27-49(62)71)53(74)67-52(36-14-7-4-8-15-36)37-16-9-5-10-17-37/h4-5,7-10,12,14-19,21,23,31-32,40,44,46-48,52,63H,1-3,11,20,22,24-30,33-34H2,(H2,62,71)(H,64,77)(H,65,75)(H,67,74)(H,66,72,76)(H2,80,81,82)/t40-,44+,46+,47?,48+/m1/s1
  • Key:JKCSCHXVWPSGBG-OPKPGBGESA-N

SD36 is an experimental anticancer drug which acts as a proteolysis targeting chimera (PROTAC) against the protein STAT3, acting by targeting this protein for destruction by cell maintenance enzymes. It has been used by a Spanish group led by Mariano Barbacid,[1] as part of a combination triple therapy alongside daraxonrasib and afatinib for treatment-resistant strains of pancreatic cancer,[2] and is also widely used for research into the treatment of other cancers and the development of related drugs.[3][4][5][6][7][8][9]

See also

References

  1. ^ "The group led by Barbacid at CNIO completely eliminates pancreatic tumours in mice with no resistance developing". Centro Nacional de Investigaciones Oncológicas (CNIO). Madrid, Spain. 29 January 2026.
  2. ^ Liaki V, Barrambana S, Kostopoulou M, Lechuga CG, Zamorano-Dominguez E, Acosta D, et al. (December 2025). "A targeted combination therapy achieves effective pancreatic cancer regression and prevents tumor resistance". Proceedings of the National Academy of Sciences of the United States of America. 122 (49) e2523039122. doi:10.1073/pnas.2523039122. PMC 12704802. PMID 41329731.
  3. ^ Bai L, Zhou H, Xu R, Zhao Y, Chinnaswamy K, McEachern D, et al. (November 2019). "A Potent and Selective Small-Molecule Degrader of STAT3 Achieves Complete Tumor Regression In Vivo". Cancer Cell. 36 (5): 498–511.e17. doi:10.1016/j.ccell.2019.10.002. PMC 6880868. PMID 31715132.
  4. ^ Zhou H, Bai L, Xu R, Zhao Y, Chen J, McEachern D, et al. (December 2019). "Structure-Based Discovery of SD-36 as a Potent, Selective, and Efficacious PROTAC Degrader of STAT3 Protein". Journal of Medicinal Chemistry. 62 (24): 11280–11300. doi:10.1021/acs.jmedchem.9b01530. PMC 8848307. PMID 31747516.
  5. ^ Kong S, Ge X, Li X, Liu Z, Zhang R, Yang M, et al. (September 2021). "SD-36 promotes growth inhibition and induces apoptosis via suppression of Mcl-1 in glioma". Journal of Cellular and Molecular Medicine. 25 (17): 8261–8270. doi:10.1111/jcmm.16754. PMC 8419162. PMID 34291563.
  6. ^ Gopalsamy A (June 2022). "Selectivity through Targeted Protein Degradation (TPD)". Journal of Medicinal Chemistry. 65 (12): 8113–8126. doi:10.1021/acs.jmedchem.2c00397. PMID 35658428.
  7. ^ Suo Y, Du D, Chen C, Zhu H, Wang X, Song N, et al. (March 2024). "Uncovering PROTAC Sensitivity and Efficacy by Multidimensional Proteome Profiling: A Case for STAT3". Journal of Medicinal Chemistry. 67 (6): 4804–4818. doi:10.1021/acs.jmedchem.3c02371. PMID 38466231.
  8. ^ Xu R, Zhou H, Bai L, McEachern D, Wu D, Acharyya RK, et al. (November 2024). "Discovery of SD-436: A Potent, Highly Selective and Efficacious STAT3 PROTAC Degrader Capable of Achieving Complete and Long-Lasting Tumor Regression". Journal of Medicinal Chemistry. 67 (22): 20495–20513. doi:10.1021/acs.jmedchem.4c01946. PMID 39509603.
  9. ^ Zhou J, Tison K, Zhou H, Bai L, Acharyya RK, McEachern D, et al. (July 2025). "STAT5 and STAT3 balance shapes dendritic cell function and tumour immunity". Nature. 643 (8071): 519–528. doi:10.1038/s41586-025-09000-3. PMC 12240842. PMID 40369063.
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