Iberdomide

Iberdomide

CAS 1323403-33-3

as HCl: 1560678-63-8

MW 449.5 g/mol, C₂₅H₂₇N₃O₅

(S)-3-(4-((4-(Morpholinomethyl)benzyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione

(3S)-3-[7-[[4-(morpholin-4-ylmethyl)phenyl]methoxy]-3-oxo-1H-isoindol-2-yl]piperidine-2,6-dione

8/13/2026, APPROVAL 2026, FDA 2026, Zenbexus, cc-220, cc 220, 8V66F27X44, 79L3645KFI

To be used in combination with daratumumab and hyaluronidase-fihj and dexamethasone for adults with multiple myeloma who have received at least one prior line of therapy, including a proteasome inhibitor and an immunomodulatory agent

Iberdomide is a modulator of the E3 ubiquitin ligase complex containing cereblon (CRL4-CRBN E3 ubiquitin ligase), with immunomodulating and pro-apoptotic activities. Upon administration, iberdomide specifically binds to the cereblon (CRBN) part of the ligase complex, thereby affecting the ubiquitin E3 ligase activity, and targeting certain substrate proteins for ubiquitination. This induces the proteasome-mediated degradation of certain transcription factors, including Ikaros (IKZF1) and Aiolos (IKZF3) which are transcriptional repressors in T-cells. This leads to a reduction of their protein levels, and the modulation of the immune system, including activation of T-lymphocytes. In addition, this leads to a downregulation of other proteins, including interferon regulatory factor 4 (IRF4), which plays a key role in the proliferation of certain cancer cell types. CRBN, the substrate recognition component of the E3 ubiquitin ligase complex, plays a key role in the ubiquitination of certain proteins.

Iberdomide, sold under the brand name Zenbexus, is an anti-cancer medication used for the treatment of multiple myeloma.^[1] It is a cereblon-modulating protein degrader^[1] and a thalidomide analog.^[2]. It is taken By mouth.^[1]

Iberdomide was approved for medical use in the United States in August 2026.^[3]

Medical uses

Iberdomide is indicated in combination with daratumumab, hyaluronidase, and dexamethasone for the treatment of adults with multiple myeloma who have received at least one prior line of therapy including a proteasome inhibitor and an immunomodulatory agent.^[3]

Society and culture

Legal status

Iberdomide was approved for medical use in the United States in August 2026.^[12] The U.S. Food and Drug Administration (FDA) granted the application for iberdomide priority review, breakthrough therapy, and orphan drug designations.^[3]

Names

Iberdomide is the international nonproprietary name.^[13]

Iberdomide is sold under the brand name Zenbexus.^[14]

SYN

compound 6 [PMID: 28425720]

SYN

https://pubs.acs.org/oprdfk/article-abstract/28/1/46/975719/Process-Development-and-Kilogram-Scale-Manufacture?redirectedFrom=fulltext

PAT

https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2011100380&_cid=P12-MSZHNS-67589-1

5.2 3-[4-(4-MORPHOLIN-4-YLMETHYL-BENZYLOXY)-1-OXO- 1,3-DIHYDRO-ISOINDOL-2-YL]-PIPERIDINE-2,6-DIONE

Step 3 : To the THF solution of methyl 5-amino-4-(4-(4- (morpholinomethyl)benzyloxy)-1-oxoisoindolin-2-yl)-5-oxopentanoate (40 g, 83 mmol), was added potassium 2-methylpropan-2-olate (9.80 g, 87 mmol) portion wise at 0°C. The mixture was stirred at this temperature for 30 minutes. To the reaction mixture, was added 45 mL of 1N HCl solution, followed by 200 mL of saturated NaHCO₃ solution. The mixture was diluted with 500 mL of EtOAc at 0°C, stirred for 5 minutes and separated. The organic layer was washed with water (50 mL × 3) and brine (100 mL), and concentrated on rota-vap to give a white solid, which was stirred in diethyl ether (300 mL) to give a suspension. The suspension was filtered to give 3-[4-(4-morpholin-4-ylmethyl-benzyloxy)-1-oxo-1,3-dihydro-isoindol-2-yl]-piperidine-2,6-dione as white solid (28.5g, 72% yield): HPLC: Waters Symmetry C₁₈, 5μm, 3.9 × 150 mm, 1 mL/min, 240 nm, gradient to 95/5 acetonitrile/0.1% H₃PO₄ in 5 min,: t_R = 4.78 min (98.5%); mp: 209-21 1 °C; ¹H NMR (DMSO-d₆) δ 1.86 – 2.09 (m, 1H, CHH), 2.29 – 2.38 (m, 4H, CH₂,CH₂), 2.44 (dd, J = 4.3, 13.0 Hz, 1H, CHH), 2.53 – 2.64 (m, 1H, CHH), 2.82 – 2.99 (m, 1H, CHH), 3.46 (s, 2H, CH₂), 3.52 – 3.61 (m, 4H, CH₂,CH₂), 4.18 – 4.51 (m, 2H, CH₂), 5.11 (dd, J = 5.0, 13.3 Hz, 1H, NCH), 5.22 (s, 2H, CH₂), 7.27 – 7.38 (m, 5H, Ar), 7.40 – 7.53 (m, 3H, Ar), 10.98 (s, 1H, NH); ¹³C NMR (DMSO-d₆) δ 22.36, 31.21, 45.09, 51.58, 53.14, 62.10, 66.17, 69.41,

114.97, 115.23, 127.64, 128.99, 129.81, 129.95, 133.31, 135.29, 137.68, 153.50, 168.01,

170.98, 172.83; LCMS: 465; Anal Calcd for C₂₅H₂₇N₃O₅ + 0.86 H₂O: C, 64.63; H, 6.22; N,

9.04; Found: C, 64.39; H, 6.11; N, 8.89; H₂O, 3.24.

5.61 (S)-3-[4-(4-MORPHOLIN-4-YLMETHYL-BENZYLOXY)-1-OXO-1,3- DIHYDRO-ISOINDOL-2-YL]-PIPERIDINE-2,6-DIONE

[386] Step 1 : Preparation of (S)-4-[4-(4-Bromomethyl-benzyloxy)-1-oxo-1,3-dihydro-isoindol-2-yl]-4-carbamoyl-butyric acid methyl ester

To a 2-L round bottom flask was charged methyl 5-amino-4-(4-hydroxy-1-oxoisoindolin-2-yl)-5-oxopentanoate (30 g, 103 mmol), 1,4-bis(bromomethyl)benzene (81 g, 308 mmol) and potassium carbonate (14.19 g, 103 mmol) and acetonitrile (1.2 L). The mixture was stirred at room temperature for 10 min and heated to 50°C for 12 hours. The reaction mixture was allowed to cool to room temperature. The mixture was filtered and the filtrate was concentrated on rota-vap. The resulted solid was dissolved in CH₂Cl₂ and loaded on 2 silica gel columns (330 g each) eluted using CH2Cl2/MeOH to give 4-[4-(4-bromomethyl-benzyloxy)-1-oxo-1,3-dihydro-isoindol-2-yl]-4-carbamoyl-butyric acid methyl ester as white solid (40g, 82%). ¹H NMR (DMSO-d₆) δ 1.98 – 2.13 (m, 1H, CHH), 2.14 – 2.23 (m, 1H, CHH), 2.23 – 2.32 (m, 2H, CHH, CHH), 3.50 (s, 3H, CH₃), 4.34 – 4.63 (m, 2H, CH₂), 4.67 – 4.80 (m, 3H, CH₂, NCH), 5.25 (s, 4H, CH₂), 7.19 (s, 1H, NHH), 7.24 – 7.34 (m, 2H, Ar), 7.41 – 7.54 (m, 5H, Ar), 7.58 (br. s., 1H, NHH)

[387] Step 2: Preparation of (S)-4-Carbamoyl-4-[4-(4-morpholin-4-ylmethyl-benzyloxy)-1-oxo-1,3-dihydro-isoindol-2-yl]-butyric acid methyl ester

To the CH₂Cl₂ solution of methyl 5-amino-4-(4-(4-(bromomethyl)benzyloxy)-1-oxoisoindolin-2-yl)-5-oxopentanoate (36.5 g, 77 mmol) was added morpholine (14.72 ml, 169 mmol) at 0 °C. The mixture was stirred at 0 °C for 1 hr. The mixture was added 200 mL of CH₂Cl₂, washed with water (100mL × 2) and brine (100 ml), dried in Na₂SO₄ and concentrated to give (S)-4-Carbamoyl-4-[4-(4-morpholin-4-ylmethyl-benzyloxy)-1-oxo-1,3-dihydro-isoindol-2-yl]-butyric acid methyl ester as white foam (39 g, 100%). M.p. 66-68 °C; Waters Symmetry C-18, 3.9 X 150 mm, 5 micro, 1 mL/min, 240 nm, isocratic 15/85 CH₃CN/ 0.1% H₃PO₄ in H₂O: 7.92 min (99%). ¹H NMR (DMSO-d₆) δ 2.00 – 2.12 (m, 1HH CHH), 2.14 – 2.22 (m, 1H, CHH), 2.22 – 2.29 (m, 2H, CHH,CHH), 2.30 – 2.39 (m, 4H, CH₂,CH₂), 3.46 (s, 2H, CH₂), 3.50 (s, 3H, CH₃), 3.53 – 3.63 (m, 4H, CH₂,CH₂), 4.28 – 4.59 (m, 2H, CH₂), 4.73 (dd, J= 4.7, 10.2 Hz, 1H, NCH), 5.22 (s, 2H, CH₂), 7.14 – 7.23 (m, 1H, NHH), 7.26 – 7.39 (m, 4H, Ar), 7.41 – 7.51 (m, 3H, Ar), 7.58 (s, 1H, NHH). ¹³C NMR (DMSO-d₆) δ 24.82, 30.33, 44.78, 51.24, 53.12, 53.38, 62.09, 66.14, 69.35, 114.66, 115.12, 127.60, 129.00, 129.55, 130.18, 133.43, 135.31, 137.66, 153.42, 167.84, 171.73, 172.46; Anal Calcd for C₂₆H₃₁N₃O₆+ 0.3 H₂O: C% 64.13; H% 6.54; N% 8.63; Found: C% 63.89; H% 6.39; N% 8.56.

[388] Step 3: Preparation of (S)-3-[4-(4-morpholin-4-ylmethyl-benzyloxy)-1-oxo- 1 , 3-dihydro-isoindol-2-yl]-piperidine-2,6-dione

To the THF solution of (S)-methyl 5-amino-4-(4-(4-(morpholinomethyl)benzyloxy)-1-oxoisoindolin-2-yl)-5-oxopentanoate (45 g, 93 mmol) was added potassium 2-methylpropan-2-olate (10.49 g, 93 mmol) portion wise (2g X5) at -78 °C. The mixture was stirred at this temperature for 30 min then was added 250 mL of 1N HCl solution followed by 200 mL of saturated NaHCO₃ solution. The mixture was extracted with CH₂Cl₂ (150 mLx2). The organic layer was washed with water (50 mL × 3) and brine (100 mL), concentrated on rota-vap to give a white solid, which was then recrystallized from CH₃CN

(100 mL) to give (S)-3-[4-(4-morpholin-4-ylmethyl-benzyloxy)-1-oxo-1,3-dihydro-isoindol-2-yl]-piperidine-2,6-dione as white solid (32g, 76%). mp: 140-142 °C. LC-MS m/e= 450. HPLC: Waters Symmetry C₁₈, 5μm, 3.9 x 150 mm, 1 mL/min, 240 nm, isocratic

15/85 CH₃CN/0.1% H₃PO₄ in 5 min,: t_R = 5.61 min (99.5%); Chiral AGP C ₁₈ 4.0 × 150 mm, 5 μm 10/90 i-propanol/ 10 mM NH₄Ac in 20 min,: t_R = 10.07 min (99.5%); ¹H NMR

(DMSO-d₆) δ 2.28 – 2.38 (m, 4H, CH₂,CH₂), 2.44 (dd, J= 4.2, 13.1 Hz, 1H, CHH), 2.53- 2.63 (m, 1H, CHH), 2.79 – 3 02 (m, 1H, CHH), 3.49 – 3.69 (m, 4H, CH₂,CH₂), 4.11 – 4.52

(m, 2H, CH₂), 5.11 (dd, J= 5.1, 13.2 Hz, 1H, NCH), 5.22 (s, 2H, CH₂), 7.33 (d, J= 7.7 Hz,

4H, Ar), 7.40 – 7.52 (m, 3H, Ar), 10.97 (s, ΙΗ, ΝΗ). ¹³C NMR (DMSO-d₆) δ 22.33, 31.18,

45.06, 51.55, 53.11, 62.07, 66.14, 69.38, 114.96, 115.20, 127.61, 128.97, 129.78, 129.93,

133.28, 135.27, 137.67, 153.48, 167.97, 170.95, 172.80. LC-MS: 465; Anal Calcd for

C₂₅H₂₇N₃O₅ C: 66.80%; H: 6.05%; N: 9.35%. Found: C:66.59%; H:5.79%; N:9.26%.

PAT

• PRMT5 inhibitors and uses thereofPublication Number:US-12448388-B2Grant Date:2025-10-21
• KRAS G12D modulating compoundsPublication Number:US-12448400-B2Grant Date:2025-10-21
• Arylmethoxy isoindoline derivatives and compositions comprising them and methods of use thereofPublication Number:ES-2956743-T3Priority Date:2010-02-11Grant Date:2023-12-27
• Arylmethoxy isoindoline derivatives and compositions comprising and methods of using the samePublication Number:AU-2013245487-A1Priority Date:2010-02-11
• Arylmethoxy isoindoline derivatives and compositions comprising and methods of using the samePublication Number:AU-2013245487-B2Priority Date:2010-02-11Grant Date:2016-03-10
• Arylmethoxy isoindoline derivatives and compositions comprising and methods of using the samePublication Number:EP-3599236-B1Priority Date:2010-02-11Grant Date:2023-08-23
• Treating cancerPublication Number:US-2025325586-A1
• Arylmethoxy isoindoline derivatives and compositions comprising and methods of using the samePublication Number:US-9822094-B2Priority Date:2010-02-11Grant Date:2017-11-21
• Arylmethoxy isoindoline derivatives and compositions comprising and methods of using the samePublication Number:EP-4289838-A2Priority Date:2010-02-11
• Arylmethoxy isoindoline derivatives and compositions comprising and methods of using the samePublication Number:US-2018037567-A1Priority Date:2010-02-11
• Arylmethoxy isoindoline derivatives and compositions comprising them and methods of using themPublication Number:ES-2713482-T3Priority Date:2010-02-11Grant Date:2019-05-22
• Arylmethoxy Isoindoline Derivatives and Compositions Comprising and Methods of Using the SamePublication Number:US-2011196150-A1Priority Date:2010-02-11

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References

References

1.  “U.S. Prescribing Information” (PDF). Packageinserts.bms.com. Retrieved 18 August 2026.
2.  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.
3.  “FDA grants accelerated approval to iberdomide with daratumumab and hyaluronidase-fihj and dexamethasone for multiple myeloma”. U.S. Food and Drug Administration (FDA). 13 August 2026. Retrieved 16 August 2026.  This article incorporates text from this source, which is in the public domain.
4.  Ye, Ying; Gaudy, Allison; Schafer, Peter; Thomas, Michael; Weiss, Daniel; Chen, Nianhang; et al. (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.
5.  Bjorklund, Chad C.; Kang, Jian; Amatangelo, Michael; Polonskaia, Ann; Katz, Mark; Chiu, Hsiling; et al. (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.
6.  van de Donk, Niels W.C.J.; Popat, Rakesh; Larsen, Jeremy; Minnema, Monique C.; Jagannath, Sundar; Oriol, Albert; et al. (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.
7.  Thieblemont, Catherine; Munoz, Javier; Tucci, Alessandra; Visco, Carlo; Cartron, Guillaume; Corradini, Paolo; et al. (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.
8.  Lonial, Sagar; Amatangelo, Michael; Popat, Rakesh; Minnema, Monique C.; Zonder, Jeffrey A.; Larsen, Jeremy; et al. (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.
9.  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.
10.  Lonial, Sagar; Popat, Rakesh; Hulin, Cyrille; Jagannath, Sundar; Oriol, Albert; Richardson, Paul G; et al. (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.
11.  Merrill, Joan T.; Werth, Victoria P.; Furie, Richard; van Vollenhoven, Ronald; Dörner, Thomas; Petronijevic, Milan; et al. (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.
12.  Feuerstein, Adam (14 August 2026). “FDA clears Bristol multiple myeloma therapy, marking debut of new drug class”. STAT. Retrieved 14 August 2026.
13.  World Health Organization (2018). “International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 79”. WHO Drug Information. 32 (1). hdl:10665/330941.
14.  “U.S. FDA Grants Accelerated Approval to Bristol Myers Squibb’s First CELMoD Therapy Zenbexus, in Combination with Daratumumab and Hyaluronidase-fihj and Dexamethasone (ZDd) for Patients with Multiple Myeloma, as Early as First Relapse”. Bristol Myers Squibb (Press release). 13 August 2026. Retrieved 16 August 2026.

External links

• “Iberdomide ( Code – C129048 )”. EVS Explore.
• “Iberdomide Hydrochloride ( Code – C141516 )”. EVS Explore.
• Clinical trial number NCT04975997 for “Open-label Study Comparing Iberdomide, Daratumumab and Dexamethasone (IberDd) Versus Daratumumab, Bortezomib, and Dexamethasone (DVd) in Participants With Relapsed or Refractory Multiple Myeloma (RRMM) (EXCALIBER-RRMM)” at ClinicalTrials.gov

Clinical data
Trade names	Zenbexus
Other names	CC-220
AHFS/Drugs.com	zenbexus
License data	US DailyMed: Iberdomide
Routes of administration	By mouth
Drug class	Cereblon-modulating protein degrader
ATC code	None
Legal status
Legal status	US: ℞-only[1]
Identifiers
IUPAC name
CAS Number	1323403-33-3as HCl: 1560678-63-8
PubChem CID	67335295as HCl: 72793904
IUPHAR/BPS	9618
DrugBank	DB12101
ChemSpider	52085251
UNII	8V66F27X44as HCl: 79L3645KFI
KEGG	D11134as HCl: D11135
ChEMBL	ChEMBL3989927
Chemical and physical data
Formula	C25H27N3O5
Molar mass	449.507 g·mol−1
3D model (JSmol)	Interactive imageas HCl: Interactive image
SMILES
InChI

////////iberdomide, ANAX LABS, APPROVAL 2026, FDA 2026, Zenbexus, APPROVAL 2026, FDA 2026, Zenbexus, cc-220, cc 220, 8V66F27X44, 79L3645KFI