CIRc-014
CIRc-014 is an orally active Cyclin A/B inhibitor with a Cyclin A IC50 of 0.05 μM, Cyclin A Kd of 2.7 nM, Cyclin B IC50 of less than 0.02 μM and Cyclin B Kd of 1.0 nM. CIRc-014 activates the spindle assembly checkpoint and promotes the formation of a complex between Cyclin B and CDK2 by blocking the RxL interaction of Cyclin A/B. CIRc-014 can induce replication stress, DNA damage, mitotic arrest and apoptosis in tumor cells. CIRc-014 showed tumor growth inhibition and regression in NCI-H69 and NCI-H446 small cell lung cancer xenograft models. CIRc-014 can be used for the research of small-cell lung cancer.
For research use only. We do not sell to patients.
- CAS No.: 3064485-73-7
- Formula: C45H62ClF6N7O7
- Molecular Weight:962.46
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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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Biological Activity
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Chemical Information
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
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Cdk1/cyclin B 1 nM (Kd) |
cdk2/cyclin A 0.05 μM (IC50) |
cdk2/cyclin A 2.7 nM (Kd) |
CIRc-014 (Compound 33) (8-point serial dilutions; 2 h) potently and selectively binds to Cyclin A and Cyclin B, with FP IC50 values of 0.050 μM and < 0.02 μM, respectively, and SPR Kd values of 2.7 nM and 1.0 nM, respectively, while showing >12-fold lower affinity for Cyclin E[1].
CIRc-014 (8-10-point serial dilutions; 3 days (WI-38); 5 days (NCI-H1048, NCI-H446, NCI-H69)) potently inhibits proliferation of SCLC cell lines NCI-H1048, NCI-H446, and NCI-H69 with GI50 values of 0.015 μM, 0.042 μM, and 0.004 μM, respectively, and is over 1270-fold less active against nontransformed WI-38 fibroblasts[1].
CIRc-014 potently and selectively inhibits cyclin A1-CDK2 with an IC50 of 0.13 μM and cyclin B-CDK1 with an IC50 below 0.02 μM, while showing significantly reduced activity against cyclin E1-CDK2 with an IC50 of 11.6 μM[2].
CIRc-014 (0.01-1000 nM; 6 days) potently inhibits proliferation of high-E2F SCLC cell lines (NCI-H1048, NCI-H446, NCI-H69)[2].
CIRc-014 (20-2000 nM; 3 days) dose-dependently induces apoptosis (measured via cleaved PARP) in high-E2F SCLC cell lines (NCI-H1048, NCI-H446, NCI-H69)[2].
CIRc-014 (20-2000 nM; 24 hours) dose-dependently induces G2/M phase arrest in high-E2F SCLC cell lines (NCI-H1048, NCI-H446, NCI-H69)[2].
CIRc-014 (300 nM; 2 hours) disrupts the cyclin B1-MYT1 protein-protein interaction in NCI-H1048 SCLC cells[2].
CIRc-014 (300 nM; 2 hours) promotes formation of neomorphic cyclin B1-CDK2 complexes in NCI-H1048 SCLC cells[2].
CIRc-014 (20-2000 nM; 24 hours) dose-dependently activates the spindle assembly checkpoint in high-E2F SCLC cell lines (NCI-H1048, NCI-H446, NCI-H69)[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:human SCLC cell lines (NCI-H1048, NCI-H446, NCI-H69, NCI-H82), NSCLC cell lines (A549, HCC4006, NCI-H1299), non-transformed RPE1 cells
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Concentration:0, 20, 200, 2000 nM
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Incubation Time:3 days
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Result:Induced cleaved PARP-positive cells in NCI-H1048 cells, NCI-H446 cells and NCI-H69 cells.
Caused < 10% cleaved PARP-positive cells across all concentrations in resistant cell lines (NCI-H82, A549, HCC4006, NCI-H1299, RPE1).
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Cell Line:human SCLC cell lines (NCI-H1048, NCI-H446, NCI-H69, NCI-H82), NSCLC cell lines (A549, HCC4006, NCI-H1299), non-transformed RPE1 cells
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Concentration:0, 20, 200, 2000 nM
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Incubation Time:24 hours
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Result:Caused dose-dependent G2/M phase accumulation in NCI-H1048 cells.
Caused G2/M phase accumulation in NCI-H446 cells.
Caused G2/M phase accumulation in NCI-H69 cells.
Induced no significant G2/M accumulation in resistant cell lines across concentrations.
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Cell Line:human SCLC cell lines (NCI-H1048, NCI-H446, NCI-H69), NSCLC cell lines (A549, HCC4006, NCI-H1299)
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Concentration:0, 20, 200, 2000 nM
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Incubation Time:24 hours
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Result:Increased p-KNL1 levels dose-dependently in sensitive SCLC lines (NCI-H1048, NCI-H446, NCI-H69).
Caused no increase in p-KNL1 levels in resistant NSCLC lines (A549, HCC4006, NCI-H1299).
| Species | Dose | Route | CL | Vd | T1/2 | Bioavailability | Tmax | Cmax | AUCinf | F |
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| Mice[1] | 2 mg/kg | i.v. | 68.05 mL/min/kg | / | 1.37 h | / | / | / | 489.86 ng·h/mL | / |
| Mice[1] | 30 mg/kg | p.o. | / | / | 0.99 h | / | 1.0 h | 1210.00 ng/mL | 2002.23 ng·h/mL | 27.2 % |
| Mice[1] | 100 mg/kg | p.o. | / | / | 3.15 h | / | 0.5 h | 2990.00 ng/mL | 8112.69 ng·h/mL | 34.9 % |
| Rat[1] | 1 mg/kg | i.v. | 46 mL/min/kg | 3.0 L/kg | 1.3 h | / | / | / | / | / |
| Dog[1] | 1 mg/kg | i.v. | 22.4 mL/min/kg | 2.6 L/kg | 4.7 h | / | / | / | / | / |
| Pig[1] | 1 mg/kg | i.v. | 28 mL/min/kg | 1.8 L/kg | 1.5 h | / | / | / | / | / |
| Mice[1] | 6 mg/mL | p.o. | / | / | / | / | / | / | / | 27.2 % |
| Rat[1] | 3 mg/mL | p.o. | / | / | / | / | / | / | / | 17.4 % |
| Dog[1] | 44.7 mg/mL | p.o. | / | / | / | 22.6 % | / | / | / | / |
| Pig[1] | 22.5 mg/mL | p.o. | / | / | / | 6.2 % | / | / | / | / |
CIRc-014 (25-100 mg/kg; p.o.; BID/TID; 14 days) induces dose-dependent tumor growth inhibition and regression in NCI-H446 SCLC xenografts[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Hsd:Athymic Nude-Foxn1nu (female, 6-7 weeks old)[1]
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Dosage:25 mg/kg; 50 mg/kg
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Administration:p.o.; BID; 14 days
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Result:Achieved 53% mean tumor growth inhibition (TGI).
Induced 40% mean tumor regression.
Resulted in mean body weight loss not exceeding 10% over the study.
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Animal Model:Hsd:Athymic Nude-Foxn1nu (female, 7-8 weeks old)[1]
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Dosage:25 mg/kg; 50 mg/kg; 100 mg/kg
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Administration:p.o.; BID/TID; 14 days
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Result:Achieved 79% mean tumor growth inhibition (TGI) at 25 mg/kg PO TID.
Achieved 85% mean TGI at 50 mg/kg PO BID.
Induced 44% mean tumor regression at 100 mg/kg PO BID.
Induced 80% mean tumor regression at 100 mg/kg PO TID.
Showed a clear dose response in tumor regrowth post-treatment, ordered from highest to lowest: 100 mg/kg PO TID, 100 mg/kg PO BID, 50 mg/kg PO BID, 25 mg/kg PO TID.
Resulted in mean body weight loss not exceeding 10% over the study.
Chemical Information
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CAS No. 3064485-73-7
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Molecular Weight 962.46
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Formula C45H62ClF6N7O7
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SMILES
O=C([C@H]1N(C(C2(C(F)(F)F)CC(F)(F)C2)=O)C[C@H](F)C1)N[C@@H](C3CC3)C(N([C@@H]4C(N[C@@H](CC(C)C)C(N(C)[C@@H](CC5=CC(Cl)=CN=C5OC6CC6)C(N(C)CCCCCCC4)=O)=O)=O)C)=O
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
[1]. Shapiro JA, et al. Orally Bioavailable Cyclin A/B RxL Inhibitors: Optimization of a Novel Class of Macrocyclic Peptides That Target E2F-High and G1-S-Checkpoint-Compromised Cancers. J Med Chem. 2026;69(5):5441-5460. [Content Brief]
[2]. Singh S, et al. Targeting G1-S-checkpoint-compromised cancers with cyclin A/B RxL inhibitors. Nature. 2025;646(8085):734-745. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
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