Iberdomide

Last updated
Iberdomide
Iberdomide.svg
Identifiers
  • (3S)-3-[7-({4-[(morpholin-4-yl)methyl]phenyl}methoxy)-3-oxo-1H-isoindol-2-yl]piperidine-2,6-dione
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
Chemical and physical data
Formula C25H27N3O5
Molar mass 449.507 g·mol−1
3D model (JSmol)
  • O=C1CC[C@H](N2Cc3c(OCc4ccc(CN5CCOCC5)cc4)cccc3C2=O)C(=O)N1
  • InChI=1S/C25H27N3O5/c29-23-9-8-21(24(30)26-23)28-15-20-19(25(28)31)2-1-3-22(20)33-16-18-6-4-17(5-7-18)14-27-10-12-32-13-11-27/h1-7,21H,8-16H2,(H,26,29,30)/t21-/m0/s1
  • Key:IXZOHGPZAQLIBH-NRFANRHFSA-N

Iberdomide (CC-220) is an experimental thalidomide analog [1] that works as an cereblon E3 ligase modulator; it has a higher binding affinity than lenalidomide or pomalidomide. It is developed by Bristol Myers Squibb for various cancers [2] [3] [4] [5] [6] [7] [8] and was also tested in people with lupus. [9]

Iberdomide has been tested in combination with Bi-specific T-cell engagers in the B-Cell Non-Hodgkin Lymphoma setting, [10] but has been dropped in favor of golcadomide (CC-99282).

References

  1. ↑ Gao, Shaobing; Wang, Shichao; Song, Yongping (December 2020). "Novel immunomodulatory drugs and neo-substrates". Biomarker Research. 8 (1): 2. doi: 10.1186/s40364-020-0182-y . PMC   6953231 . PMID   31938543.
  2. ↑ Ye, Ying; Gaudy, Allison; Schafer, Peter; Thomas, Michael; Weiss, Daniel; Chen, Nianhang; Liu, Liangang; Xue, Yongjun; Carayannopoulos, Leon; Palmisano, Maria (May 2021). "First-in-Human, Single- and Multiple-Ascending-Dose Studies in Healthy Subjects to Assess Pharmacokinetics, Pharmacodynamics, and Safety/Tolerability of Iberdomide, a Novel Cereblon E3 Ligase Modulator". Clinical Pharmacology in Drug Development. 10 (5): 471–485. doi:10.1002/cpdd.869. PMC   8246954 . PMID   32969202.
  3. ↑ Bjorklund, Chad C.; Kang, Jian; Amatangelo, Michael; Polonskaia, Ann; Katz, Mark; Chiu, Hsiling; Couto, Suzana; Wang, Maria; Ren, Yan; Ortiz, Maria; Towfic, Fadi; Flynt, J. Erin; Pierceall, William; Thakurta, Anjan (April 2020). "Iberdomide (CC-220) is a potent cereblon E3 ligase modulator with antitumor and immunostimulatory activities in lenalidomide- and pomalidomide-resistant multiple myeloma cells with dysregulated CRBN". Leukemia. 34 (4): 1197–1201. doi:10.1038/s41375-019-0620-8. ISSN   1476-5551. PMC   7214241 . PMID   31719682.
  4. ↑ van de Donk, Niels W.C.J.; Popat, Rakesh; Larsen, Jeremy; Minnema, Monique C.; Jagannath, Sundar; Oriol, Albert; Zonder, Jeffrey; Richardson, Paul G.; Rodriguez-Otero, Paula; Badros, Ashraf Z.; Stadtmauer, Edward; Bringhen, Sara; Campagnaro, Erica; Siegel, David S.; Gamberi, Barbara; Gironella Mesa, Mercedes; Sonneveld, Pieter; Nguyen, Tuong Vi; Di Micco, Antonia; Sorrell, April; Chen, Min; Amatangelo, Michael; Kueenburg, Elisabeth; Lonial, Sagar (5 November 2020). "First Results of Iberdomide (IBER; CC-220) in Combination with Dexamethasone (DEX) and Daratumumab (DARA) or Bortezomib (BORT) in Patients with Relapsed/Refractory Multiple Myeloma (RRMM)". Blood. 136 (Supplement 1): 16–17. doi: 10.1182/blood-2020-137743 . S2CID   228828103.
  5. ↑ Thieblemont, Catherine; Munoz, Javier; Tucci, Alessandra; Visco, Carlo; Cartron, Guillaume; Corradini, Paolo; Flinn, Ian W.; Gastinne, Thomas; Bouabdallah, Kamal Krimo; Arcaini, Luca; Nowakowski, Grzegorz S.; Roulin, Louise; Topp, Max; Jauhari, Shekeab; Vucinic, Vladan; Martin, Peter; Gkasiamis, Argyrios; Drew, James; Rao, Parth; Kaplan, Mark; Cheng, Yiming; Li, Ju; Morschhauser, Franck (15 November 2022). "Iberdomide (CC-220) Monotherapy or in Combination with an Anti-CD20 Monoclonal Antibody As Effective Therapy in Patients with Relapsed/Refractory Lymphoma: Early Results from a Phase 1/2 Study". Blood. 140 (Supplement 1): 569–572. doi: 10.1182/blood-2022-162559 . S2CID   256795199.
  6. ↑ Lonial, Sagar; Amatangelo, Michael; Popat, Rakesh; Minnema, Monique C.; Zonder, Jeffrey A.; Larsen, Jeremy; Oriol Rocafiguera, Albert; Campagnaro, Erica L.; Rodriguez Otero, Paula; Badros, Ashraf Z.; Siegel, David S.; Jagannath, Sundar; Bringhen, Sara; Gironella, Mercedes; Kaiser, Martin F.; Cook, Gordon; Gamberi, Barbara; Sonneveld, Pieter; Nguyen, Tuong Vi; Chen, Min S.; Homan, Trevor; Bjorklund, Chad C.; Wang, Maria; Pierceall, William E.; Bensmaine, Amine; Thakurta, Anjan; Peluso, Teresa; Van De Donk, Niels W. C. J. (13 November 2019). "Translational and Clinical Evidence of a Differentiated Profile for the Novel CELMoD, Iberdomide (CC-220)". Blood. 134 (Supplement_1): 3119. doi: 10.1182/blood-2019-124298 . S2CID   209233746.
  7. ↑ Amatangelo, Michael; Bjorklund, Chad C.; Kang, Jian; Polonskaia, Ann; Viswanatha, Sridevi; Thakurta, Anjan (29 November 2018). "Iberdomide (CC-220) Has Synergistic Anti-Tumor and Immunostimulatory Activity Against Multiple Myeloma in Combination with Both Bortezomib and Dexamethasone, or in Combination with Daratumumab in Vitro". Blood. 132 (Supplement 1): 1935. doi: 10.1182/blood-2018-99-113383 . S2CID   91382999.
  8. ↑ Lonial, Sagar; Popat, Rakesh; Hulin, Cyrille; Jagannath, Sundar; Oriol, Albert; Richardson, Paul G; Facon, Thierry; Weisel, Katja; Larsen, Jeremy T; Minnema, Monique C; Abdallah, Al-Ola; Badros, Ashraf Z; Knop, Stefan; Stadtmauer, Edward A; Cheng, Yiming; Amatangelo, Michael; Chen, Min; Nguyen, Tuong Vi; Amin, Alpesh; Peluso, Teresa; van de Donk, Niels W C J (November 2022). "Iberdomide plus dexamethasone in heavily pretreated late-line relapsed or refractory multiple myeloma (CC-220-MM-001): a multicentre, multicohort, open-label, phase 1/2 trial". The Lancet Haematology. 9 (11): e822 –e832. doi:10.1016/S2352-3026(22)00290-3. PMID   36209764. S2CID   252779185.
  9. ↑ Merrill, Joan T.; Werth, Victoria P.; Furie, Richard; van Vollenhoven, Ronald; Dörner, Thomas; Petronijevic, Milan; Velasco, Jorge; Majdan, Maria; Irazoque-Palazuelos, Fedra; Weiswasser, Michael; Korish, Shimon; Ye, Ying; Gaudy, Allison; Schafer, Peter H.; Liu, Zhaohui; Agafonova, Nataliya; Delev, Nikolay (17 March 2022). "Phase 2 Trial of Iberdomide in Systemic Lupus Erythematosus". New England Journal of Medicine. 386 (11): 1034–1045. doi: 10.1056/NEJMoa2106535 . PMID   35294813. S2CID   247499089.
  10. ↑ "A Study Evaluating the Safety, Pharmacokinetics, and Efficacy of Mosunetuzumab or Glofitamab in Combination With CC-220 and/or CC-99282 in Participants With B-Cell Non-Hodgkin Lymphoma". clinicaltrials.gov. 4 May 2025.
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