Tibremciclib
Tibremciclib (BPI-16350) is an orally active CDK4/6 inhibitor. Tibremciclib selectively inhibits CDK4/cyclin D1 and CDK6/cyclin D1 with IC50 values of 2.21 nM and 0.407 nM, respectively. Tibremciclib blocks Rb phosphorylation and cell cycle progression, and induces G1 phase arrest in Rb-positive tumor cells, exhibiting broad-spectrum anti-tumor cell proliferation activity. Tibremciclib inhibits MATE1 and MATE2-K. Tibremciclib dose-dependently inhibits tumor growth in xenograft models, and shows synergistic effects when combined with Fulvestrant (HY-13636). Tibremciclib can be used for research related to breast cancer.
For research use only. We do not sell to patients.
- CAS No.: 2397678-18-9
- Formula: C28H32F2N8
- Molecular Weight:518.60
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
Biological Activity
Description
IC50 & Target
[1]|
CDK4/cyclinD1 2.21 nM (IC50) |
CDK6/cyclinD1 0.407 nM (IC50) |
Cdk4/cyclin D3 4.19 nM (IC50) |
cdk6/cyclin D3 10.2 nM (IC50) |
CDK9/cyclinT1 91.9 nM (IC50) |
Cdk5/p25 344 nM (IC50) |
Cellular Effect
|
Cell Line
|
Type | Value | Description | References |
|---|---|---|---|---|
| JeKo-1 | IC50 |
36.4 nM
|
Inhibition of viability in human JeKo-1 cells incubated 96 hrs by CellTiter-Glo assay.
Inhibition of viability in human JeKo-1 cells incubated 96 hrs by CellTiter-Glo assay.
|
628f2434-2d23-4d6c-87ed-53f282c9d435.pdf |
| MV4-11 | IC50 |
87.0 nM
|
Inhibition of viability in human MV-4-11 cells incubated 96 hrs by CellTiter-Glo assay.
Inhibition of viability in human MV-4-11 cells incubated 96 hrs by CellTiter-Glo assay.
|
628f2434-2d23-4d6c-87ed-53f282c9d435.pdf |
| COLO 205 | IC50 |
371.8 nM
|
Inhibition of viability in human COLO 205 cells incubated 120 hrs by CellTiter-Glo assay.
Inhibition of viability in human COLO 205 cells incubated 120 hrs by CellTiter-Glo assay.
|
628f2434-2d23-4d6c-87ed-53f282c9d435.pdf |
| MDA-MB-468 | IC50 |
4583 nM
|
Inhibition of viability in human MDA-MB-468 cells incubated 96 hrs by CellTiter-Glo assay.
Inhibition of viability in human MDA-MB-468 cells incubated 96 hrs by CellTiter-Glo assay.
|
628f2434-2d23-4d6c-87ed-53f282c9d435.pdf |
| T47D | IC50 |
37.2 nM
|
Antiproliferative activity against human T-47D cells assessed as BrdU incorporation incubated 96 hrs by DELFIA assay.
Antiproliferative activity against human T-47D cells assessed as BrdU incorporation incubated 96 hrs by DELFIA assay.
|
628f2434-2d23-4d6c-87ed-53f282c9d435.pdf |
| MDA-MB-361 | IC50 |
56.8 nM
|
Antiproliferative activity against human MDA-MB-361 cells assessed as BrdU incorporation incubated 96 hrs by DELFIA assay.
Antiproliferative activity against human MDA-MB-361 cells assessed as BrdU incorporation incubated 96 hrs by DELFIA assay.
|
628f2434-2d23-4d6c-87ed-53f282c9d435.pdf |
| MCF7 | IC50 |
84.8 nM
|
Antiproliferative activity against human MCF-7 cells assessed as BrdU incorporation incubated 96 hrs by DELFIA assay.
Antiproliferative activity against human MCF-7 cells assessed as BrdU incorporation incubated 96 hrs by DELFIA assay.
|
628f2434-2d23-4d6c-87ed-53f282c9d435.pdf |
| MDA-MB-361 | IC50 |
5.4 nM
|
Induction of G1 arrest in human MDA-MB-361 cells incubated 24 hrs by propidium iodide flow cytometry.
Induction of G1 arrest in human MDA-MB-361 cells incubated 24 hrs by propidium iodide flow cytometry.
|
628f2434-2d23-4d6c-87ed-53f282c9d435.pdf |
| BT-474 | IC50 |
6.9 nM
|
Induction of G1 arrest in human BT-474 cells incubated 24 hrs by propidium iodide flow cytometry.
Induction of G1 arrest in human BT-474 cells incubated 24 hrs by propidium iodide flow cytometry.
|
628f2434-2d23-4d6c-87ed-53f282c9d435.pdf |
| T47D | IC50 |
14.2 nM
|
Induction of G1 arrest in human T-47D cells incubated 24 hrs by propidium iodide flow cytometry.
Induction of G1 arrest in human T-47D cells incubated 24 hrs by propidium iodide flow cytometry.
|
628f2434-2d23-4d6c-87ed-53f282c9d435.pdf |
| ZR-75-1 | IC50 |
20.9 nM
|
Induction of G1 arrest in human ZR-75-1 cells incubated 24 hrs by propidium iodide flow cytometry.
Induction of G1 arrest in human ZR-75-1 cells incubated 24 hrs by propidium iodide flow cytometry.
|
628f2434-2d23-4d6c-87ed-53f282c9d435.pdf |
| MDA-MB-231 | IC50 |
28.2 nM
|
Induction of G1 arrest in human MDA-MB-231 cells incubated 24 hrs by propidium iodide flow cytometry.
Induction of G1 arrest in human MDA-MB-231 cells incubated 24 hrs by propidium iodide flow cytometry.
|
628f2434-2d23-4d6c-87ed-53f282c9d435.pdf |
| JeKo-1 | IC50 |
28.5 nM
|
Induction of G1 arrest in human JeKo-1 cells incubated 24 hrs by propidium iodide flow cytometry.
Induction of G1 arrest in human JeKo-1 cells incubated 24 hrs by propidium iodide flow cytometry.
|
628f2434-2d23-4d6c-87ed-53f282c9d435.pdf |
| MV4-11 | IC50 |
59.7 nM
|
Induction of G1 arrest in human MV-4-11 cells incubated 24 hrs by propidium iodide flow cytometry.
Induction of G1 arrest in human MV-4-11 cells incubated 24 hrs by propidium iodide flow cytometry.
|
628f2434-2d23-4d6c-87ed-53f282c9d435.pdf |
| COLO 205 | IC50 |
93.0 nM
|
Induction of G1 arrest in human COLO 205 cells incubated 24 hrs by propidium iodide flow cytometry.
Induction of G1 arrest in human COLO 205 cells incubated 24 hrs by propidium iodide flow cytometry.
|
628f2434-2d23-4d6c-87ed-53f282c9d435.pdf |
| NCI-H1299 | IC50 |
113.7 nM
|
Induction of G1 arrest in human NCI-H1299 cells incubated 24 hrs by propidium iodide flow cytometry.
Induction of G1 arrest in human NCI-H1299 cells incubated 24 hrs by propidium iodide flow cytometry.
|
628f2434-2d23-4d6c-87ed-53f282c9d435.pdf |
| MDA-MB-468 | IC50 |
>20000 nM
|
Induction of G1 arrest in human MDA-MB-468 cells incubated 24 hrs by propidium iodide flow cytometry with IC50 greater than 20000 nM.
Induction of G1 arrest in human MDA-MB-468 cells incubated 24 hrs by propidium iodide flow cytometry with IC50 greater than 20000 nM.
|
628f2434-2d23-4d6c-87ed-53f282c9d435.pdf |
In Vitro
Tibremciclib (4.6-30000 nM; 96 h-120 h) inhibits the viability of Rb-positive JeKo-1, MV-4-11, and COLO 205 cells with IC50 values of 36.4, 87.0, and 371.8 nM, respectively, but exhibits weaker activity in Rb-negative MDA-MB-468 cells (IC50 of 4583 nM)[1].
Tibremciclib (4.6-30000 nM; 96 h) inhibits the proliferation of Rb-positive T-47D, MDA-MB-361, and MCF-7 cells with IC50 values of 37.2, 56.8, and 84.8 nM, respectively, and exhibits synergistic effects with Fulvestrant (HY-13636) in T-47D cells[1].
Tibremciclib (3 nM-20 µM; 24 h) induces dose-dependent G1 phase arrest in Rb-positive cancer cell lines, with IC50 values of 5.4 to 113.7 nM, but has no such effect in Rb-negative MDA-MB-468 cells (>20000 nM)[1].
Tibremciclib is a potent and selective CDK4/6 inhibitor with IC50 values of 2.21, 0.407, 4.19, and 10.2 nM for CDK4/cyclin D1, CDK6/cyclin D1, CDK4/cyclin D3, and CDK6/cyclin D3, respectively, and weaker activity against CDK9/cyclinT1 (IC50 91.9 nM)[1].
Tibremciclib exhibits high permeability in Caco-2 cells, is likely not a potent efflux substrate, and has some inhibitory effect on P-glycoprotein and breast cancer resistance protein[1].
Tibremciclib inhibits MATE1 and MATE2-K, with IC50 values of 21.2 μM and 65.4 μM, respectively[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:JeKo-1, MV-4-11, COLO 205, and MDA-MB-468 cells
-
Concentration:4.6, 13.7, 41.1, 123, 370, 1111, 3333, 10000, 30000 nM
-
Incubation Time:96 h; 120 h
-
Result:IC50 values were 36.4 nM for JeKo-1, 87.0 nM for MV-4-11, 371.8 nM for COLO 205, and 4583 nM for MDA-MB-468 (Rb-negative).
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Cell Line:T-47D, MCF-7, and MDA-MB-361 cells
-
Concentration:4.6, 13.7, 41.1, 123, 370, 1111, 3333, 10000, 30000 nM
-
Incubation Time:96 h
-
Result:IC50 values were 37.2 nM for T-47D, 56.8 nM for MDA-MB-361, and 84.8 nM for MCF-7.
Combination with fulvestrant yielded synergistic anti-proliferation effects on T-47D cells.
-
Cell Line:MDA-MB-361, BT-474, T-47D, ZR-75-1, MDA-MB-231, JeKo-1, MV-4-11, COLO 205, NCI-H1299, and MDA-MB-468 cells
-
Concentration:0.003, 0.009, 0.028, 0.08, 0.25, 0.74, 2.2, 6.67 and 20 µM
-
Incubation Time:24 h
-
Result:G1 arrest IC50 values were 5.4 nM for MDA-MB-361, 6.9 nM for BT-474, 14.2 nM for T-47D, 20.9 nM for ZR-75-1, 28.2 nM for MDA-MB-231, 28.5 nM for JeKo-1, 59.7 nM for MV-4-11, 93.0 nM for COLO 205, 113.7 nM for NCI-H1299, and >20000 nM for MDA-MB-468.
The proportion of cells in G0/G1 phase increased from about 50-95% following exposure to 3 nM to 20 µM in Rb-positive cells, with no such effect in Rb-negative MDA-MB-468 cells at concentrations up to 20 µM.
Parmacokinetics
In Vivo
Tibremciclib (25-100 mg/kg; oral gavage) inhibits JeKo-1 xenograft tumor growth, with up to 104.5% inhibition[1].
Tibremciclib (25-100 mg/kg; oral gavage) inhibits MV-4-11 xenograft tumor growth by up to 67.7%[1].
Tibremciclib (oral gavage) inhibits Rb phosphorylation in COLO 205 xenograft tumors[1].
Tibremciclib combined with Fulvestrant (HY-13636) produces a synergistic antitumor effect in MCF-7 xenograft tumors without obvious toxicity[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
- Somatic Cell Culture
- Breast Cancer Modeling
- Flow cytometric DNA-content cell-cycle staining
- MTT Cell Proliferation Assay
- Western Blot
- BrdU Incorporation Assay
- CFSE Dye Dilution Proliferation Assay
- Dye-dilution cell tracking and proliferation staining
- Patient-Derived Orthotopic Xenograft (PDOX)
- Protocol for Cell Cycle
- CCK-8/WST-8 Cell Proliferation Assay
- Cell Counting-Based Growth Curve Assay
- Colony Formation (Clonogenic) Assay
- Cell Viability Determination by MTT Colorimetric Assay
- Kinase activity and phosphorylation assays
- EdU Incorporation Assay (Click Chemistry-Based DNA Synthesis Measurement)
- Ki-67 Immunostaining Proliferation Assay
- PCNA Immunodetection Proliferation Assay
- Protocol for Cell Counting and Cell Density Analysis
- Patient-Derived Xenograft (PDX)
- Splenic/Portal-Vein Liver Metastasis Xenograft
- Protocol for Kinase activity and phosphorylation assays
- Subcutaneous Cell-Line-Derived Xenograft
- Orthotopic Cell-Line Xenograft
- Intraperitoneal/Peritoneal Dissemination Xenograft
Chemical Information
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CAS No. 2397678-18-9
-
Molecular Weight 518.60
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Formula C28H32F2N8
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SMILES
C[C@H]1N2C3=CC(C4=NC(NC5=CC=C(C=N5)CN6CCN(CC6)CC)=NC=C4F)=CC(F)=C3N=C2CCC1
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Synonyms
BPI-16350
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Shipping
Room temperature in continental US; may vary elsewhere.
-
Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)