Iberdomide

Last updated
Iberdomide
Iberdomide.svg
Identifiers
  • (3S)-3-[7-[[4-(Morpholin-4-ylmethyl)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)
  • C1CC(=O)NC(=O)[C@H]1N2CC3=C(C2=O)C=CC=C3OCC4=CC=C(C=C4)CN5CCOCC5
  • 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 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]

Related Research Articles

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Multiple myeloma (MM), also known as plasma cell myeloma and simply myeloma, is a cancer of plasma cells, a type of white blood cell that normally produces antibodies. Often, no symptoms are noticed initially. As it progresses, bone pain, anemia, kidney dysfunction, and infections may occur. Complications may include hypercalcemia and amyloidosis.

<span class="mw-page-title-main">Lenalidomide</span> Pair of enantiomers

Lenalidomide, sold under the brand name Revlimid among others, is a medication used to treat multiple myeloma, smoldering myeloma, and myelodysplastic syndromes (MDS). For multiple myeloma, it is a first line treatment, and is given with dexamethasone. It is taken by mouth.

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Bortezomib, sold under the brand name Velcade among others, is an anti-cancer medication used to treat multiple myeloma and mantle cell lymphoma. This includes multiple myeloma in those who have and have not previously received treatment. It is generally used together with other medications. It is given by injection.

<span class="mw-page-title-main">B-cell maturation antigen</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">Plasma cell leukemia</span> Medical condition

Plasma cell leukemia (PCL) is a plasma cell dyscrasia, i.e. a disease involving the malignant degeneration of a subtype of white blood cells called plasma cells. It is the terminal stage and most aggressive form of these dyscrasias, constituting 2% to 4% of all cases of plasma cell malignancies. PCL may present as primary plasma cell leukemia, i.e. in patients without prior history of a plasma cell dyscrasia or as secondary plasma cell dyscrasia, i.e. in patients previously diagnosed with a history of its predecessor dyscrasia, multiple myeloma. The two forms of PCL appear to be at least partially distinct from each other. In all cases, however, PCL is an extremely serious, life-threatening, and therapeutically challenging disease.

<span class="mw-page-title-main">Pomalidomide</span> Chemical compound

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<span class="mw-page-title-main">Daratumumab</span> Monoclonal antibody

Daratumumab, sold under the brand name Darzalex, is an anti-cancer monoclonal antibody medication. It binds to CD38, which is overexpressed in multiple myeloma cells. Daratumumab was originally developed by Genmab, but it is now being jointly developed by Genmab along with the Johnson & Johnson subsidiary Janssen Biotech, which acquired worldwide commercialization rights to the drug from Genmab.

Smouldering myeloma is a disease classified as intermediate in a spectrum of step-wise progressive diseases termed plasma cell dyscrasias. In this spectrum of diseases, a clone of plasma cells secreting monoclonal paraprotein causes the relatively benign disease of monoclonal gammopathy of undetermined significance. This clone proliferates and may slowly evolve into more aggressive sub-clones that cause smouldering multiple myeloma. Further and more rapid evolution causes the overtly malignant stage of multiple myeloma and can subsequently lead to the extremely malignant stage of secondary plasma cell leukemia. Thus, some patients with smouldering myeloma progress to multiple myeloma and plasma cell leukemia. Smouldering myeloma, however, is not a malignant disease. It is characterised as a pre-malignant disease that lacks symptoms but is associated with bone marrow biopsy showing the presence of an abnormal number of clonal myeloma cells, blood and/or urine containing a myeloma protein, and a significant risk of developing into a malignant disease.

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Isatuximab, sold under the brand name Sarclisa, is a monoclonal antibody (mAb) medication for the treatment of multiple myeloma.

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Ixazomib is a drug for the treatment of multiple myeloma, a type of white blood cell cancer, in combination with other drugs. It is taken by mouth in the form of capsules.

<span class="mw-page-title-main">Melphalan flufenamide</span> Alkylating type cancer drug

Melphalan flufenamide, sold under the brand names Pepaxto and Pepaxti, is an anticancer medication used to treat multiple myeloma.

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Selinexor sold under the brand name Xpovio among others, is a selective inhibitor of nuclear export used as an anti-cancer medication. It works by blocking the action of exportin 1 and thus blocking the transport of several proteins involved in cancer-cell growth from the cell nucleus to the cytoplasm, which ultimately arrests the cell cycle and leads to apoptosis. It is the first drug with this mechanism of action.

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Idecabtagene vicleucel, sold under the brand name Abecma, is a cell-based gene therapy to treat multiple myeloma.

Monoclonal gammopathy of renal significance (MGRS) are a group of kidney disorders that present with kidney damage due to nephrotoxic monoclonal immunoglobulins secreted by clonal plasma cells or B cells. By definition, people with MGRS do not meet criteria for multiple myeloma or other hematologic malignancies. The term MGRS was introduced in 2012 by the International Kidney and Monoclonal Gammopathy Research Group (IKMG). MGRS is associated with monoclonal gammopathy of undetermined significance (MGUS). People with MGUS have a monoclonal gammopathy but does not meet the criteria for the clonal burden nor the presence of end organ damage seen in hematologic malignancies. In a population based study based on the NHANES III health survey; 6% of patients with MGUS were subsequently classified as having MGRS. The prevalence and incidence of MGRS in the general population or in specific populations is not known but it is more prevalent in those over the age of 50 as there is a monoclonal protein (M-protein) present in 3% of those 50 and years older and 5% of those 70 years and older, placing those 50 and older at increased risk of MGRS.

DarwinHealth is an American biomedical company that uses algorithms and mathematical models in combination with wet lab experiments to develop cancer medicine. It is headquartered in New York, U.S.

<span class="mw-page-title-main">Mezigdomide</span> Chemical compound

Mezigdomide is a cereblon E3 ligase modulator developed by Bristol Myers Squibb to treat multiple myeloma.

<span class="mw-page-title-main">Avadomide</span> Chemical compound

Avadomide is an experimental cereblon E3 ligase modulator, or thalidomide analog studied to see if it is effective against cancer.

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.