Golcadomide (CC99282; CC-99282) is a cereblon (CRBN) E3 ligase modulator (CELMoD) with anticancer (non-Hodgkin lymphoma) activity. It can induce the degradation of Ikaros and Aiolos.

Physicochemical Properties

Molecular Formula	C28H30FN5O5
Molecular Weight	535.57
Exact Mass	535.223
CAS #	2379572-34-4
PubChem CID	146195299
Appearance	Light yellow to yellow solid powder
LogP	1.6
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	9
Rotatable Bond Count	7
Heavy Atom Count	39
Complexity	970
Defined Atom Stereocenter Count	1
SMILES	C12=C(C(N([C@H]3CCC(NC3=O)=O)C1=O)=O)C(NCC1=C(F)C=C(C=C1)CN1CC(C1)N1CCOCC1)=CC=C2
InChi Key	NZYDBVQXOGPDDU-QHCPKHFHSA-N
InChi Code	InChI=1S/C28H30FN5O5/c29-21-12-17(14-32-15-19(16-32)33-8-10-39-11-9-33)4-5-18(21)13-30-22-3-1-2-20-25(22)28(38)34(27(20)37)23-6-7-24(35)31-26(23)36/h1-5,12,19,23,30H,6-11,13-16H2,(H,31,35,36)/t23-/m0/s1
Chemical Name	2-[(3S)-2,6-dioxopiperidin-3-yl]-4-[[2-fluoro-4-[(3-morpholin-4-ylazetidin-1-yl)methyl]phenyl]methylamino]isoindole-1,3-dione
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

References

[1]. A PHASE 1, MULTICENTER, OPEN-LABEL STUDY OF CC-99282 ALONE AND IN COMBINATION WITH RITUXIMAB IN PATIENTS WITH RELAPSED OR REFRACTORY NON-HODGKIN LYMPHOMAS. Hematological Oncology. Volume 39, Issue S2, Jun. 2021. [2]. CC-99282 is a novel cereblon (CRBN) E3 ligase modulator (CELMoD) agent with enhanced tumoricidal activity in preclinical models of lymphoma. Blood, 2021, 138: 1200.

Additional Infomation

Golcadomide is a modulator of the E3 ubiquitin ligase complex containing cereblon (CRL4-CRBN E3 ubiquitin ligase), with potential immunomodulating and antineoplastic activities. Upon administration, golcadomide specifically binds to cereblon (CRBN), thereby affecting the ubiquitin E3 ligase activity, and targeting certain substrate proteins for ubiquitination. This induces proteasome-mediated degradation of certain transcription factors, some of which are transcriptional repressors in T-cells. This leads to modulation of the immune system, including activation of T-lymphocytes, and downregulation of the activity of other proteins, some of which play key roles in the proliferation of certain cancer cell types. CRBN, the substrate recognition component of the CRL4-CRBN E3 ubiquitin ligase complex, plays a key role in the ubiquitination of certain proteins.

Solubility Data

Solubility (In Vitro)

DMSO : ~125 mg/mL (~233.40 mM)

Solubility (In Vivo)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.8672 mL	9.3358 mL	18.6717 mL
	5 mM	0.3734 mL	1.8672 mL	3.7343 mL
	10 mM	0.1867 mL	0.9336 mL	1.8672 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.