Trilaciclib

Catalog No.S8389 Batch:S838901

Technical Data

Formula

C₂₄H₃₀N₈O

Molecular Weight

446.55

CAS No.

1374743-00-6

Solubility (25°C)*

In vitro

0.1M HCl

3.75 mg/mL (8.39 mM)

DMSO

Insoluble

Water

Insoluble

In vivo (Add solvents to the product individually and in order)

5%0.1MHCL 1 40%PEG300 2 5%Tween80 3 50%ddH2O

0.15mg/ml

* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description

Trilaciclib is a highly potent, selective and reversible cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor. Trilaciclib inhibits CDK4/cyclin D1 and CDK6/cyclin D3 with IC50 of 1 nM and 4 nM, respectively.

Targets

CDK4/cyclin D1 ^[1] (Cell-free assay)	CDK6/cyclin D3 ^[1] (Cell-free assay)
1 nM	4 nM

In vitro

G1T28 is a potent and selective CDK4/6 inhibitor that inhibits the phosphorylation of RB and induces an exclusive, reversible G1 arrest. In vitro and in vivo, G1T28 protects RB competent cells from damage by chemotherapy as assessed by gamma-H2A.X (γH2AX) and apoptosis through caspase 3/7 activation.^[1]

In vivo

In vivo, G1T28 regulates the proliferation of HSPCs in both mouse and canine bone marrow, in a reversible, doseand time-dependent manner. Pretreatment of mice with G1T28 allows a faster recovery of complete blood counts (CBCs) following chemotherapy. In addition, G1T28 does not protect RB deficient tumors from chemotherapy but, instead, adds to the anti-tumor effect.^[1]

Protocol (from reference)

Cell Assay:^{^[1]}	Cell lines HS68 cells, WM2664 cells, A2058 cells Concentrations 10 nM, 30 nM, 100 nM, 300 nM, 1000 nM Incubation Time 4 h, 8 h, 16 h, 24 h Method HS68, WM2664 and A2058 cells are treated with 300 nM G1T28 or DMSO (0.1%), for 4, 8, 16 or 24 hours. Whole cell extracts are prepared using 1× radioimmunoprecipitation assay buffer (RIPA) containing 1× HALT protease and phosphatase inhibitors. Total protein concentration is determined by using the bicinchoninic acid (BCA) Protein Assay Kit, according to manufacturer's instructions. Fifteen micrograms of protein is heat denatured for 10 minutes at 70 ℃ and resolved by Novex NuPAGE SDS-PAGE gel system and transferred to 0.45 μm nitrocellulose membrane by electroblotting. Membranes are blocked in LiCor Membrane Blocking Buffer and incubated overnight with rabbit anti-pRb (Ser807/811) antibody at a 1:1,000 dilution and mouse anti-MAPK antibody at a 1:2,000 dilution, as a loading control. Secondary antibodies (LiCor) are Goat anti- rabbit (680RD) and Goat antimouse (800CW) at a 1:15,000 dilution. Blots are incubated for one hour, washed and imaged using LiCor ImageStudio software.
Animal Study:^{^[1]}	Animal Models 8-week-old female FVB mice Dosages 50 mg/kg, 100 mg/kg, 150 mg/kg Administration Oral gavage

Cell Assay:^{^[1]}

Cell lines
HS68 cells, WM2664 cells, A2058 cells
Concentrations
10 nM, 30 nM, 100 nM, 300 nM, 1000 nM
Incubation Time
4 h, 8 h, 16 h, 24 h
Method
HS68, WM2664 and A2058 cells are treated with 300 nM G1T28 or DMSO (0.1%), for 4, 8, 16 or 24 hours. Whole cell extracts are prepared using 1× radioimmunoprecipitation assay buffer (RIPA) containing 1× HALT protease and phosphatase inhibitors. Total protein concentration is determined by using the bicinchoninic acid (BCA) Protein Assay Kit, according to manufacturer's instructions. Fifteen micrograms of protein is heat denatured for 10 minutes at 70 ℃ and resolved by Novex NuPAGE SDS-PAGE gel system and transferred to 0.45 μm nitrocellulose membrane by electroblotting. Membranes are blocked in LiCor Membrane Blocking Buffer and incubated overnight with rabbit anti-pRb (Ser807/811) antibody at a 1:1,000 dilution and mouse anti-MAPK antibody at a 1:2,000 dilution, as a loading control. Secondary antibodies (LiCor) are Goat anti- rabbit (680RD) and Goat antimouse (800CW) at a 1:15,000 dilution. Blots are incubated for one hour, washed and imaged using LiCor ImageStudio software.

Animal Study:^{^[1]}

Animal Models
8-week-old female FVB mice
Dosages
50 mg/kg, 100 mg/kg, 150 mg/kg
Administration
Oral gavage

References

RETURN POLICY
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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.