Cemsidomide (CFT7455) is an orally bioactive degrader of the zinc finger transcription factors Ikaros (IKZF1) and Aiolos (IKZF3). Cemsidomide is an anti-cancer compound that binds cereblon E3 ligase with high affinity (Kd 0.9 nM) (WO2022032132A1; Compound 1).

Physicochemical Properties

Molecular Formula	C28H27N3O4
Molecular Weight	469.53
Exact Mass	469.2
CAS #	2504235-67-8
PubChem CID	155207651
Appearance	Light yellow to green yellow solid powder
LogP	2.9
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	5
Heavy Atom Count	35
Complexity	819
Defined Atom Stereocenter Count	1
SMILES	O=C1[C@@H](N2C(=O)C3=C4C(C(CC5=CC=C(C=C5)CN5CCOCC5)=CC=C24)=CC=C3)CCC(=O)N1
InChi Key	MUKCJOOKCZSQNW-DEOSSOPVSA-N
InChi Code	InChI=1S/C28H27N3O4/c32-25-11-10-24(27(33)29-25)31-23-9-8-20(21-2-1-3-22(26(21)23)28(31)34)16-18-4-6-19(7-5-18)17-30-12-14-35-15-13-30/h1-9,24H,10-17H2,(H,29,32,33)/t24-/m0/s1
Chemical Name	(3S)-3-[6-[[4-(morpholin-4-ylmethyl)phenyl]methyl]-2-oxobenzo[cd]indol-1-yl]piperidine-2,6-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

ln Vitro	In multiple myeloma cells, cemsidomide stimulates the degradation of >75% of steady-state IKZF1 in 1.5 hours at 0.3 nM. Both NCIH929 cells resistant to both lenalidomide and pomalidomide (IC50 of 2.3 nM) and previously untreated NCIH929 multiple myeloma cell lines (IC50 of 0.071 nM) are efficiently inhibited by the strong binding affinity and degradation catalysis of CFT7455 [1]. When applied to IMiD-resistant H929 cells and multiple myeloma cells, cemsidomide exhibits strong antiproliferative action [2].
ln Vivo	Cemsidomide showed dose-dependent effectiveness in mice xenograft tumor models, with doses ranging from 3 μg/kg/day to 100 μg/kg/day. In many tumor xenograft experiments, cemsidomide administered daily at doses ranging from 30 μg/kg/day to 100 μg/kg/day produced long-lasting tumor regression [1]. In a H929 tumor xenograft model, cemsidomide (0.1 mg/kg/day; for 21 days) promotes tumor regression (95% tumor growth suppression at 7 days) [2].
References	[1]. Advantageous therapies for disorders mediated by ikaros or aiolos. WO2022032132A1. [2]. Abstract LB007: CFT7455: A novel, IKZF1/3 degrader that demonstrates potent tumor regression in IMiD-resistant multiple myeloma (MM) xenograft models. Cancer Res (2021) 81 (13_Supplement): LB007.
Additional Infomation	Cemsidomide is an orally bioavailable modulator of the E3 ubiquitin ligase complex containing cereblon (CRL4-CRBN E3 ubiquitin ligase), with potential immunomodulating and antineoplastic activities. Upon oral administration, cemsidomide 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, including Ikaros (IKZF1) and Aiolos (IKZF3), which are transcriptional repressors in T-cells. This reduces the levels of these transcription factors, and modulates the activity of the immune system, which may include the activation of T-lymphocytes. This also leads to 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 : ~25 mg/mL (~53.24 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (5.32 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.32 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.1298 mL	10.6489 mL	21.2979 mL
	5 mM	0.4260 mL	2.1298 mL	4.2596 mL
	10 mM	0.2130 mL	1.0649 mL	2.1298 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.