| Size | Price | |
|---|---|---|
| 1mg | ||
| 5mg | ||
| 10mg | ||
| Other Sizes |
| Targets |
CFT7455 is a novel degrader targeting Ikaros family zinc finger proteins IKZF1 and IKZF3. It induces degradation of IKZF1/3 through high-affinity binding to cereblon (CRBN), a component of the CRL4-CRBN E3 ubiquitin ligase complex [2].
|
|---|---|
| ln Vitro |
CFT7455 demonstrated an 800-fold improvement in CRBN binding in biochemical assays and a 1,600-fold improvement in cellular NanoBRET assays compared to pomalidomide [2].
In H929 multiple myeloma cells expressing HiBiT-tagged IKZF1, CFT7455 induced over 75% degradation of IKZF1 within 1.5 hours [2]. CFT7455 exhibited potent antiproliferative activity across a panel of multiple myeloma cell lines, as well as in H929 cells that had acquired resistance to immunomodulatory drugs (IMiDs) [2]. |
| ln Vivo |
RPMI-8226 Mouse Xenograft Model: In mice bearing RPMI-8226 xenografts, treatment with CFT7455 (0.1 mg/kg/day) resulted in deep and durable degradation of IKZF3, with protein levels reduced to 21% and 9.5% of vehicle control at 4 hours and 24 hours post-dose, respectively. IRF4 protein levels declined to 8% of vehicle levels over 7 days of daily treatment. Dose-dependent efficacy was observed across a range of 0.003 to 0.1 mg/kg/day, with tumor regression evident at doses ≥0.01 mg/kg/day. In this model, pomalidomide was inactive at a human equivalent dose of 3 mg/kg/day, with no observed tumor shrinkage after 17 days. Switching from pomalidomide to CFT7455 (0.1 mg/kg/day) on day 18 led to tumor regression in 67% of animals by day 28 and 100% tumor regression by day 35 [2].
H929 Tumor Xenograft Model: In mice bearing H929 tumor xenografts, administration of CFT7455 (0.1 mg/kg/day) promoted tumor regression with 95% tumor growth inhibition by day 7. Dosing was stopped after 21 days. By day 63, half of the tumors remained below their starting tumor volume [2]. MM1.S Systemic Tumor Model: CFT7455 demonstrated durable tumor regression in the aggressive MM1.S systemic multiple myeloma model [2]. Combination with Dexamethasone: In mice bearing RPMI-8226 xenografts, the combination of CFT7455 (daily dosing) and dexamethasone (weekly dosing) was more active than either agent alone and demonstrated a significant improvement in survival [2]. |
| Enzyme Assay |
Biochemical CRBN Binding Assay: The binding affinity of CFT7455 to cereblon (CRBN) was determined using a biochemical binding assay. Compared to pomalidomide, CFT7455 demonstrated an 800-fold improvement in CRBN binding [2].
|
| Cell Assay |
Cellular NanoBRET Assay: The cellular binding of CFT7455 to CRBN was assessed using a NanoBRET assay. Compared to pomalidomide, CFT7455 demonstrated a 1,600-fold improvement in CRBN binding in this cellular context [2].
HiBiT-Tagged IKZF1 Degradation Assay: H929 multiple myeloma cells expressing HiBiT-tagged IKZF1 were treated with CFT7455. The degradation of IKZF1 was measured, showing that the compound induced over 75% degradation within 1.5 hours [2]. Antiproliferative Activity Assay: The antiproliferative activity of CFT7455 was evaluated across a panel of multiple myeloma cell lines, including H929 cells that had developed resistance to immunomodulatory drugs. Potent activity was observed in these assays [2]. |
| Animal Protocol |
RPMI-8226 Xenograft Model: Mice bearing RPMI-8226 tumor xenografts were used. CFT7455 was administered at doses ranging from 0.003 to 0.1 mg/kg/day. Pomalidomide was administered at 3 mg/kg/day as a comparator. In a separate arm, animals initially treated with pomalidomide were switched to CFT7455 (0.1 mg/kg/day) on day 18 [2].
H929 Xenograft Model: Mice bearing H929 tumor xenografts were treated with CFT7455 at 0.1 mg/kg/day. Dosing was discontinued after 21 days [2]. MM1.S Systemic Tumor Model: The activity of CFT7455 was also evaluated in the aggressive MM1.S systemic multiple myeloma model [2]. Combination Study: In mice bearing RPMI-8226 xenografts, the combination of CFT7455 (administered once daily, QD) and dexamethasone (administered once weekly, QW) was evaluated for efficacy and survival improvement [2]. |
| ADME/Pharmacokinetics |
Cemsidomide is administered orally and exhibits dose-proportional increases in systemic exposure. The molecular formula is C28H27N3O4, with a molecular weight of 469.53 g/mol. It has a predicted logP of 2.86 and a pKa (strongest basic) of 7.01. The compound is characterized by high cereblon binding affinity, enabling rapid, deep, and durable degradation of its target proteins IKZF1 and IKZF3
|
| Toxicity/Toxicokinetics |
The most frequently observed treatment-emergent adverse events (TEAEs) are hematologic in nature. Grade 3-4 adverse events occurring in ≥10% of patients include neutropenia (34%), anemia (28%), infections (19%), lymphopenia (16%), and thrombocytopenia (13%). No grade 3/4 fatigue, nausea, or vomiting were reported. One dose-limiting toxicity (Grade 4 neutropenia lasting >7 days) was observed. No patients experienced grade 3/4 fatigue, nausea, or vomiting. Myelosuppression has been reported as manageable.
|
| References | |
| Additional Infomation |
Background: IKZF1 and IKZF3 are essential transcription factors for terminal differentiation of B and T cells. Depletion of IKZF1/3 in multiple myeloma cells inhibits growth. Immunomodulatory drugs (IMiDs) such as lenalidomide and pomalidomide promote degradation of IKZF1/3 via CRBN, but acquired resistance frequently develops [2].
Mechanism: CFT7455 is a catalytic degrader of IKZF1/3, optimized for high-affinity CRBN binding and rapid target degradation. It demonstrates high binding affinity and degradation catalysis, enabling potent antiproliferative activity even in IMiD-resistant cells [2]. Clinical Status: Based on the preclinical results showing potent antitumor activity as a single agent and in combination with dexamethasone, as well as activity in IMiD-resistant models, a clinical study is planned to investigate CFT7455 as a therapeutic approach for multiple myeloma [2]. |
| Molecular Formula |
C28H27N3O4
|
|---|---|
| Molecular Weight |
469.53
|
| Exact Mass |
469.2
|
| Elemental Analysis |
C, 71.62; H, 5.80; N, 8.95; O, 13.63
|
| CAS # |
2504233-68-3
|
| Related CAS # |
Cemsidomide;2504235-67-8
|
| PubChem CID |
155194819
|
| Appearance |
Light yellow to 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 |
0
|
| SMILES |
N1C(=O)CCC(N2C3=C4C(C=CC=C4C2=O)=C(CC2=CC=C(CN4CCOCC4)C=C2)C=C3)C1=O
|
| InChi Key |
MUKCJOOKCZSQNW-UHFFFAOYSA-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)
|
| Chemical Name |
3-[6-[[4-(morpholin-4-ylmethyl)phenyl]methyl]-2-oxobenzo[cd]indol-1-yl]piperidine-2,6-dione
|
| Synonyms |
(Rac)-Cemsidomide; (Rac)-CFT-7455; 2504233-68-3; (Rac)-CFT7455; (Rac)-CFT 7455; 3-(6-(4-(Morpholinomethyl)benzyl)-2-oxobenzo[cd]indol-1(2H)-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)
|
| Solubility (In Vitro) |
DMSO : ~62.5 mg/mL (~133.11 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.43 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 20.8 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.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
