Lerociclib dihydrochloride (G1T38 dihydrochloride) 是一种有效的选择性 CDK4/CDK6 抑制剂，抑制 CDK4/CyclinD1 和 CDK6/CyclinD3，IC₅₀ 值分别为 1 nM 和 2 nM。

Lerociclib dihydrochloride (G1T38 dihydrochloride) is a potent and selective inhibitor of CDK4/CDK6, with IC 50 s of 1 nM and 2 nM for CDK4/CyclinD1 and CDK6/CyclinD3, respectively.

Solid

Cdk4/cyclin D1 1 nM (IC50) cdk6/cyclin D3

Within the CDK family, Lerocyclib is least selective against CDK9/cyclin T, ~30 fold between CDK4/cyclin D1 and CDK9/ cyclin T at the biochemical IC50. Lerociclib produces a robust and sustained G1 arrest in CDK4/6 dependent cells with an EC50 of ~20 nM. A dose dependent increase of cells in the G1 phase of the cell cycle is observed when CDK4/6 dependent WM2664 cells are treated with G1T38 for 24 hours. This arrest is maintained through 300 nM, more than 300x the biochemical IC50. WM2664 cells treated with 30-1000 nM of Lerociclib for 24 hours exhibits a complete inhibition of RB phosphorylation compared to vehicle controls. Treatment with G1T38 reduces RB phosphorylation within 1 hour post-treatment and generates near complete inhibition of RB phosphorylation by 16 hours post-treatment. G1T38 produces a robust inhibition of proliferation in a

In this HER2 breast cancer model, Mice treated with Lerociclib elicits 8% tumor regression after 21 days of treatment while control animals have a 577% increase in tumor burden over the same treatment period. Compared to the vehicle-treated mice, daily treatment with 100 mg/kg of Lerociclib or palbociclib shows tumor regression within 10 days in the MCF7 xenograft model. After 27 days of treatment, tumor growth inhibition is observed in the 10, 50, and 100 mg/kg Lerociclib cohorts (approximately 12%, 74%, and 90% inhibition, respectively). Daily oral palbociclib treatment causes an 18%, 66%, and 87% tumor growth inhibition in the 10, 50, and 100 mg/kg dosage cohorts, respectively. Interestingly, at 50 mg/kg, Lerociclib is significantly more efficaciou than palbociclib. Similar results are seen in the ER ZR-75-1 breast cancer xenograft model when comparing Lerocyclib and palboc

Room temperature in continental US; may vary elsewhere.

4°C, sealed storage, away from moistur In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

[1]. Bisi JE, et al. Preclinical development of G1T38: A novel, potent and selective inhibitor of cyclin dependent kinases 4/6 for use as an oral antineoplastic in patients with CDK4/6 sensitive tumors. Oncotarget. 2017 Jun 27;8(26):42343-42358.

In Vitro: H₂O : 4 mg/mL (7.31 mM; Need ultrasonic)配制储备液