CID-078
Based on 1 Customer Validation
CID-078 is an orally active macrocyclic cyclin A and cyclin B inhibitor. CID-078 binds cyclin hydrophobic patches, disrupting interactions of cyclin A-Cdk2 with E2F1 and cyclin B-Cdk1 with Myt1, and selectively targets RxL binding motifs to block complex-substrate interactions. CID-078 induces DNA damage, G2/M cell cycle arrest, apoptosis, mitotic catastrophe, spindle assembly checkpoint activation, and neomorphic cyclin B-CDK2 complex formation, driving synthetic lethality in E2F-driven cancer cells. CID-078 can be used for the research of small cell lung cancer, non-small cell lung cancer, triple negative breast cancer, advanced solid tumors, luminal HR+/HER2- breast cancer, RB1-altered solid tumors, and neuroblastoma.
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研究用途以外に使用した場合、当社は一切の責任を負いかねます。
- 純度 : 99.07%
- CAS 番号: 3064485-16-8
- 分子式: C47H63ClF6N8O6
- 分子量:985.50
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保管条件:Powder -20°C, 3 years ; In solvent -80°C, 6 months , -20°C, 1 month
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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生物活性
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化学情報
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溶剤 & 溶解度
- プロトコル
- 純度とドキュメンテーション
- 参考文献
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Help & FAQs
生物活性
製品説明
体外実験
CID-078 induces antiproliferation in 46 SCLC and 104 NSCLC cell lines, with enhanced activity observed in cells with high E2F and G2M hallmark pathway scores and/or elevated cyclin B1 and separase expression[1].
CID-078 (4-8 days) inhibits proliferation of a broad panel of solid tumor cell lines, with significantly greater potency (lower GI50 values) in RB1-altered cell lines, and heightened sensitivity correlated with high E2F targets and G2/M checkpoint pathway scores in SCLC, TNBC, and NSCLC cell lines[3].
CID-078 binds to the hydrophobic patch/RxL binding site of cyclin-CDK complexes, inhibits E2F1-cyclin A-CDK2 and MYT1-cyclin B-CDK1 interactions, and induces replication stress, DNA damage, and mitotic catastrophe in E2F1-high tumor cells[3].
CID-078 (72 h) inhibits growth of established neuroblastoma cell lines with GI50 values ranging from 0.001 μM (SKNSH) to 10 μM (SY5Y WT, GIMEN, TR14, SKNAS)[4].
CID-078 (72 h) sensitizes CDKN2A-inactivated SH-SY5Y neuroblastoma cells, resulting in GI50 values of 55 nM (C7.3 clone) and 6 nM (C8.10 clone) compared to >10 μM in wild-type SH-SY5Y cells[4].
CID-078 (120 h) inhibits growth of patient-derived neuroblastoma organoid models with GI50 values ranging from 0.01 μM to 1 μM[4].
CID-078 (100 nM; 24 h) induces G2/M-phase cell cycle arrest in neuroblastoma cell lines, with percentage increases in G2/M population ranging from 52% (SY5Y C7.3) to 632% (SKNSH) compared to DMSO control[4].
CID-078 (3-200 nM; 24 h) induces spindle assembly checkpoint activation (phospho-BUBR1), DNA damage (phospho-γH2AX), and G2/M phase marker expression (phospho-FoxM1) in neuroblastoma cell lines and hTERT-RPE1 healthy control cells[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
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Cell Line:SY5Y C7.3, TR14, SY5Y C8.10, SY5Y WT, SHEP2, HDN33, SKNAS, GIMEN, NGP, SJNB6, NMB, SKNSH
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Concentration:100 nM
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Incubation Time:24 h
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Result:Increased the G2/M-phase population compared to DMSO control, with percentage increases ranging from 52% (SY5Y C7.3) to 632% (SKNSH).
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Cell Line:SY5Y WT, SY5Y C7.3, SY5Y C8.10, SJNB6, SKNSH, TR14, HDN33, GIMEN, SKNAS, hTERT-RPE1
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Concentration:20 nM, 200 nM
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Incubation Time:24 h
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Result:Induced phosphorylation of BUBR1 (SAC activation) in SY5Y WT, SY5Y C7.3, SY5Y C8.10, SJNB6, and hTERT-RPE1 cells at 20 nM and 200 nM.
Induced phosphorylation of γH2AX (DNA damage) in SY5Y WT, SY5Y C7.3, SY5Y C8.10, SJNB6, and SKNSH cells at 20 nM and 200 nM; in TR14 and HDN33 cells at 3 nM, 30 nM, and 100 nM.
Induced phosphorylation of FoxM1 (G2/M phase marker) in SY5Y WT, SY5Y C7.3, SY5Y C8.10, GIMEN, and SKNAS cells at 3 nM and 100 nM.
体内実験
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
化学情報
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CAS 番号 3064485-16-8
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性状 Solid
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分子量 985.50
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分子式 C47H63ClF6N8O6
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Color White to off-white
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SMILES
ClC1=CC=C(C2=CN(C)N=C2)C(C[C@H](N(C([C@H](CC(C)C)NC3=O)=O)C)C(N(CCCCCCC[C@@H]3N(C([C@H](C4CC4)NC([C@@H]5C[C@@H](F)CN5C(C6(C(F)(F)F)CC(F)(F)C6)=O)=O)=O)C)C)=O)=C1
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輸送条件
Room temperature in continental US; may vary elsewhere.
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保管条件
Powder -20°C 3 years In solvent -80°C 6 months -20°C 1 month
溶剤 & 溶解度
体外:
DMSO : 100 mg/mL (101.47 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
濃度 (開始) × 体積 (開始) = 濃度 (終了) × 体積 (終了)
体内:
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: 2.5 mg/mL (2.54 mM); Suspended solution; Need ultrasonic
This protocol yields a suspended solution of 2.5 mg/mL. Suspended solution can be used for oral and intraperitoneal injection.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.5 mg/mL (2.54 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
プロトコル
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Detection of Apoptosis
Apoptosis, also called programmed cell death, is generally characterized by distinct morphological characteristics.
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TUNEL staining for apoptotic DNA fragmentation
TUNEL staining detects DNA strand breaks by using terminal deoxynucleotidyl transferase to add labeled nucleotides to exposed 3′-OH DNA termini, generating either microscopic staining in fixed cells or tissue sections, or fluorescence/cytometric signal in cell suspensions. TUNEL positivity reflects DNA fragmentation but should not be interpreted alone as definitive apoptosis, because TUNEL can also label necrotic, autolytic, mechanically damaged, or DNA-repair-associated DNA breaks.
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Flow cytometric DNA-content cell-cycle staining
Flow cytometric DNA-content cell-cycle staining measures the fluorescence intensity of DNA-bound fluorochromes in single cells or nuclei to estimate DNA content distributions, allowing assignment of populations to G0/G1, S, and G2/M phases by DNA histogram deconvolution. Propidium iodide (PI) intercalates into DNA, and PI fluorescence is proportional to cellular DNA content when staining is performed under conditions that make DNA accessible and minimize non-DNA signal. Cells with G2/M DNA content are expected to show approximately twice the fluorescence intensity of G0/G1 cells, while S-phase cells occupy intermediate fluorescence values. PI-based DNA-content analysis can also detect cells with fractional DNA content, often reported as sub-G1, when DNA fragmentation and extraction during staining reduce retained DNA signal in apoptotic cells. DAPI is an alternative DNA fluorochrome for univariate DNA-content analysis, while bivariate approaches combining DNA content with proliferation
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Annexin V plus membrane-impermeant dye apoptosis staining
Annexin V-based apoptosis assays rely on the detection of phosphatidylserine (PS) externalization from the inner leaflet of the plasma membrane to the outer leaflet, an early biochemical hallmark of apoptosis. Fluorescently labeled Annexin V binds PS in a calcium-dependent manner, enabling identification of early apoptotic cells by flow cytometry or fluorescence microscopy. When combined with a membrane-impermeant DNA-binding dye (e. g. , propidium iodide), this approach allows discrimination between viable (Annexin V−/dye−), early apoptotic (Annexin V+/dye−), and late apoptotic or necrotic (Annexin V+/dye+) cell populations by assessing membrane integrity and PS exposure.
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BrdU Incorporation Assay
Bromodeoxyuridine (BrdU) incorporation assay is based on the principle that BrdU, a thymidine analog, is incorporated into newly synthesized DNA during the S phase of the cell cycle, thereby serving as a marker of DNA replication and cellular proliferation. Incorporated BrdU can be detected using anti-BrdU antibodies following DNA denaturation, enabling visualization or quantification of proliferating cells through immunochemical detection methods such as immunofluorescence or immunohistochemistry.
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Apoptosis Solutions
Apoptosis is a regulated, generally non-lytic cell-death pathway that removes unwanted, damaged, infected, or abnormal cells through coordinated morphological changes, caspase activation, DNA fragmentation, and membrane remodeling. The intrinsic apoptosis pathway is controlled mainly by mitochondrial outer membrane permeabilization, BCL-2 family proteins, cytochrome c release, apoptosome formation, caspase-9 activation, and downstream executioner caspase-3/7 activation. The extrinsic apoptosis pathway is initiated by death receptors such as Fas, TNFR, and TRAIL receptors, which recruit adaptor proteins and activate caspase-8 before engaging executioner caspases or mitochondrial amplification through BID cleavage. Apoptosis is linked to many phenotypes, including cancer cell killing, tissue homeostasis, immune regulation, neurodegeneration, infection response, and treatment-induced cytotoxicity; unresolved questions include how apoptosis interacts with necroptosis, pyroptosis, ferroptos
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Protocol for Cell Cycle
Cell-cycle analysis by flow cytometry measures DNA content in single cells to estimate the fraction of cells in G0/G1, S, and G2/M phases. Propidium iodide intercalates into DNA, and after RNA removal with RNase, fluorescence intensity reflects cellular DNA content: 2N cells are assigned to G0/G1, cells between 2N and 4N to S phase, and 4N cells to G2/M. DNA-content analysis alone cannot reliably separate G0 from G1 or G2 from M. Ki-67 can distinguish quiescent G0 cells from cycling cells, EdU or BrdU incorporation marks active DNA synthesis in S phase, and phospho-histone H3 staining identifies mitotic cells within the 4N population.
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Breast Cancer Modeling
Breast cancer is a heterogeneous cancer, and it has been distinguished into four subtypes: luminal A, luminal B, HER2-positive and basal-like. Molecular mutations, epigenetic alterations, hormone exposure and immune microenvironment are related to the progression of breast cancer.
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Genotoxicity/Mutagenicity Study
The bacterial reverse mutation assay detects point mutations that restore amino-acid prototrophy in auxotrophic Salmonella typhimurium or Escherichia coli tester strains; after exposure to a test article, mutagenic activity is read out as an increased number of revertant colonies on minimal agar compared with the vehicle control. The assay uses tester strains with different mutation targets so that base-substitution and frameshift mutagens can be detected, and testing is performed with and without exogenous mammalian metabolic activation because some chemicals require biotransformation to become mutagenic.
純度とドキュメンテーション
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データシート (281 KB)
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SDS (252 KB)
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取扱説明書 (2659 KB)
参考文献
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
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| DMSO | 1 mM | 1.0147 mL | 5.0736 mL | 10.1471 mL | 25.3678 mL |
| 5 mM | 0.2029 mL | 1.0147 mL | 2.0294 mL | 5.0736 mL | |
| 10 mM | 0.1015 mL | 0.5074 mL | 1.0147 mL | 2.5368 mL | |
| 15 mM | 0.0676 mL | 0.3382 mL | 0.6765 mL | 1.6912 mL | |
| 20 mM | 0.0507 mL | 0.2537 mL | 0.5074 mL | 1.2684 mL | |
| 25 mM | 0.0406 mL | 0.2029 mL | 0.4059 mL | 1.0147 mL | |
| 30 mM | 0.0338 mL | 0.1691 mL | 0.3382 mL | 0.8456 mL | |
| 40 mM | 0.0254 mL | 0.1268 mL | 0.2537 mL | 0.6342 mL | |
| 50 mM | 0.0203 mL | 0.1015 mL | 0.2029 mL | 0.5074 mL | |
| 60 mM | 0.0169 mL | 0.0846 mL | 0.1691 mL | 0.4228 mL | |
| 80 mM | 0.0127 mL | 0.0634 mL | 0.1268 mL | 0.3171 mL | |
| 100 mM | 0.0101 mL | 0.0507 mL | 0.1015 mL | 0.2537 mL |
CID-078 関連分類
HY-183118 関連分類
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