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| Targets |
CCI 007 exhibits selective cytotoxicity against MLL-rearranged leukemia cells[1][2]
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| ln Vitro |
CCI-007 is a leukemia that selectively inhibits MLL-r, CALM-AF10, and SET-NUP214 [1]. After CCI-007 treatment for 24 hours, PER-485 cells showed significant mitochondrial depolarization as shown by alterations in the JC-1 signal. In susceptible cells, CCI-007 alters the typical MLL-r gene expression profile and suppresses the expression of BCL2, MEIS1, CMYC, HOXA9, and MEIS1 [1]. Resistance to CCI-007 may result from upregulation of MLL target gene expression [1].
Selective antiproliferative activity against MLL-rearranged leukemia cells: - MV4-11 (MLL-AF4): IC₅₀ = 0.32 μM (MTT assay); 1 μM inhibited cell proliferation by 85% [1] - THP-1 (MLL-AF9): IC₅₀ = 0.45 μM (MTT assay); 1.5 μM reduced cell viability to 22% [1] - MONO-MAC-6 (MLL-AF9): IC₅₀ = 0.51 μM (CCK-8 assay) [1] - Low cytotoxicity against non-MLL-rearranged cells: - K562 (CML, BCR-ABL⁺): IC₅₀ > 10 μM [1] - HL-60 (AML, no MLL rearrangement): IC₅₀ > 8 μM [1] - Normal human cord blood CD34⁺ cells: Cell viability >90% at 2 μM [1] - Apoptosis induction in MLL-rearranged cells: - 0.5 μM CCI 007 increased apoptotic rate of MV4-11 cells by 62% (Annexin V-FITC/PI staining); upregulated cleaved caspase-3/caspase-9 by 3.2–4.1-fold and Bax by 2.3-fold, downregulated Bcl-2 by 58% (Western blot) [1] - 0.8 μM induced PARP cleavage in THP-1 cells (Western blot) [1] - Mitochondrial dysfunction induction: - 0.3–1 μM dose-dependently increased intracellular reactive oxygen species (ROS) by 2.5–4.8-fold in MV4-11 cells (DCFH-DA fluorescence assay) [2] - 0.5 μM reduced mitochondrial membrane potential (Δψm) by 65% (JC-1 staining, flow cytometry) [2] - 0.8 μM decreased ATP production by 72% and impaired mitochondrial respiration (seahorse assay) [2] - Inhibition of clonogenic potential: 0.4 μM CCI 007 reduced MV4-11 colony formation by 82% (methylcellulose colony assay) [1] |
| ln Vivo |
Antitumor activity in MLL-rearranged leukemia xenograft models:
- MV4-11 xenograft (BALB/c nude mice): Intraperitoneal administration of CCI 007 (5, 10 mg/kg, once daily for 21 days) dose-dependently inhibited tumor growth, reducing tumor volume by 55% (5 mg/kg) and 78% (10 mg/kg) compared to vehicle [1] - THP-1 xenograft (NOD/SCID mice): 10 mg/kg CCI 007 (ip, qd for 14 days) reduced tumor weight by 68%; immunohistochemical analysis showed increased cleaved caspase-3 (2.8-fold) and reduced Ki-67 (62%) in tumor tissues [1] - No obvious systemic toxicity: Treated mice showed no significant body weight loss (<6% change) or histopathological abnormalities in liver, kidney, spleen, or heart [1][2] |
| Cell Assay |
Cell viability assay[1]
Cell Types: PER-485, MOLM-13, MV4; 11 cells. Tested Concentrations: 5μM. Incubation Duration: 24 hrs (hours). Experimental Results: Induction of apoptosis. Antiproliferation assay: MLL-rearranged (MV4-11, THP-1) and non-MLL-rearranged (K562, HL-60) leukemia cells were seeded in 96-well plates (5×10³ cells/well), cultured for 24 hours, and treated with CCI 007 (0.1–10 μM) for 72 hours. MTT/CCK-8 reagent was added to measure absorbance at 570/450 nm, calculating cell viability and IC₅₀ [1] - Apoptosis assay: MV4-11/THP-1 cells were treated with CCI 007 (0.3–1 μM) for 48 hours, stained with Annexin V-FITC and PI, and apoptotic cells were quantified by flow cytometry; Western blot detected apoptotic markers (cleaved caspase-3/9, Bax, Bcl-2, PARP) [1] - Mitochondrial function assays: - ROS detection: MV4-11 cells were loaded with DCFH-DA probe for 30 minutes, treated with CCI 007 (0.3–1 μM) for 24 hours, and fluorescence intensity was measured to quantify ROS levels [2] - Mitochondrial membrane potential assay: Cells were stained with JC-1 dye for 20 minutes after drug treatment (0.3–1 μM, 24 hours), and red/green fluorescence ratio was analyzed by flow cytometry to assess Δψm [2] - ATP production assay: Drug-treated cells (0.3–1 μM, 24 hours) were lysed, and ATP levels were quantified by luciferase-based assay [2] - Colony formation assay: MV4-11 cells were seeded in methylcellulose medium (2×10³ cells/well) with CCI 007 (0.1–0.8 μM), cultured for 14 days, and colonies were counted [1] - Normal cell toxicity assay: Human cord blood CD34⁺ cells were isolated and treated with CCI 007 (0.5–2 μM) for 72 hours, and cell viability was measured by MTT assay [1] |
| Animal Protocol |
MV4-11 xenograft model: 6–8 weeks old BALB/c nude mice were subcutaneously injected with MV4-11 cells (5×10⁶ cells/mouse) into the right flank. When tumors reached ~100 mm³, mice were randomly divided into vehicle group, CCI 007 5 mg/kg group, and 10 mg/kg group [1]
- THP-1 xenograft model: 6–8 weeks old NOD/SCID mice were subcutaneously injected with THP-1 cells (1×10⁷ cells/mouse). Tumors of ~120 mm³ were treated with CCI 007 10 mg/kg [1] - Drug formulation: CCI 007 was dissolved in dimethyl sulfoxide (DMSO) and diluted with normal saline to a final DMSO concentration of ≤5% [1][2] - Administration protocol: The compound was administered via intraperitoneal injection once daily for 14–21 days. Tumor volume (length×width²/2) and body weight were measured every 3 days [1] - Sample collection: At the end of treatment, mice were euthanized. Tumors were excised, weighed, and fixed in formalin for immunohistochemical staining (cleaved caspase-3, Ki-67); major organs were collected for histopathological examination [1] |
| Toxicity/Toxicokinetics |
In vitro toxicity: - In non-MLL rearranged leukemia cells (K562, HL-60), CC₅₀ > 10 μM [1] - At a concentration of 2 μM, the cell viability of normal human umbilical cord blood CD34⁺ cells > 90% [1] - In vivo toxicity: - Acute toxicity: Mice injected intraperitoneally with doses up to 50 mg/kg of CCI 007 did not show death or obvious toxic symptoms (drowsiness, diarrhea) [1] - Subchronic toxicity (21 days, mice): CCI 007 (10 mg/kg, intraperitoneal injection, once daily) did not cause significant changes in hematological parameters (white blood cells, red blood cells, platelets) or liver and kidney function indicators (ALT, AST, creatinine) [1] - Plasma protein binding: 88% (mouse plasma, ultrafiltration) [1]
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| References |
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| Additional Infomation |
CCI 007 is a synthetic small molecule compound with selective cytotoxicity against MLL rearranged infantile leukemia cells[1][2]. Its antitumor mechanism involves inducing mitochondrial dysfunction, including excessive production of reactive oxygen species (ROS), mitochondrial membrane potential collapse, ATP depletion, and impaired respiration, ultimately leading to caspase-dependent apoptosis[2]. MLL rearrangement is common in infantile acute leukemia and is associated with poor prognosis; CCI 007 specifically targets this subset of leukemia cells with very low toxicity to normal hematopoietic cells[1]. The compound has shown potent antitumor activity against MLL rearranged leukemia both in vitro and in vivo, supporting its potential as a targeted therapy for this high-risk disease[1][2].
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| Molecular Formula |
C15H16N2O5S
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|---|---|
| Molecular Weight |
336.362942695618
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| Exact Mass |
336.077
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| CAS # |
939228-52-1
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| Related CAS # |
939228-52-1
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| PubChem CID |
154792594
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| Appearance |
Solid
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| LogP |
2.5
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
23
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| Complexity |
508
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CCOC(=O)COC1=C(C=C(C=C1)/C=C/2\C(=O)NC(=N)S2)OC
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| InChi Key |
KGSKTLMBOLPOTC-KPKJPENVSA-N
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| InChi Code |
InChI=1S/C15H16N2O5S/c1-3-21-13(18)8-22-10-5-4-9(6-11(10)20-2)7-12-14(19)17-15(16)23-12/h4-7H,3,8H2,1-2H3,(H2,16,17,19)/b12-7+
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| Chemical Name |
ethyl 2-[4-[(E)-(2-imino-4-oxo-1,3-thiazolidin-5-ylidene)methyl]-2-methoxyphenoxy]acetate
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| Synonyms |
CCI 007; CCI-007; CCI007
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: 67~83.3 mg/mL (199.2~247.7 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (6.18 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 | 2.9730 mL | 14.8650 mL | 29.7301 mL | |
| 5 mM | 0.5946 mL | 2.9730 mL | 5.9460 mL | |
| 10 mM | 0.2973 mL | 1.4865 mL | 2.9730 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.
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