Lerociclib dihydrochloride

SKU: orb1309651

Description

Lerociclib dihydrochloride (G1T38) is a highly potent and selective CDK4/6 inhibitor, demonstrating IC50 values of 1 nM and 2 nM against CDK4/CyclinD1 and CDK6/CyclinD3, respectively. It is a valuable research tool for investigating cell cycle progression and has shown antitumor activity in preclinical models of breast cancer and other malignancies.

Research Area

Cell Biology

Key Properties

• CAS Number: 2097938-59-3
• MW: 547.52
• Purity: 97.40%
• Formula: C₂₆H₃₆Cl₂N₈O
• SMILES: Cl.Cl.CC(C)N1CCN(CC1)c1ccc(Nc2ncc3cc4C(=O)NCC5(CCCCC5)n4c3n2)nc1
• Target: CDK
• Solubility: H2O:95 mg/mL (173.51 mM);DMSO:1 mg/mL (1.83 mM);Saline:50 mg/mL (91.32 mM)

Bioactivity

• Target IC50:
  CDK9-CyclinT:28 nM|CDK2-CyclinA:1.5 μM|CDK4-CyclinD1:1 nM|CDK2-CyclinE:3.6 μM|CDK5-p25:1.2 μM|CDK7-CyclinH-MAT1:2.4 μM|CDK5-p35:832 nM|CDK1-cyclinB1:2.4 μM|CDK6-CyclinD3:2 nM
• In Vivo:
  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.
• In Vitro:
  Lerociclib robustly induces sustained G1 arrest in CDK4/6 dependent cells with an EC50 of ~20 nM. A dose-dependent increase in G1 phase is observed when CDK4/6 dependent WM2664 cells are treated with G1T38 for 24 hours, maintaining this arrest up to 300 nM. WM2664 cells exhibit complete inhibition of RB phosphorylation at 30-1000 nM of Lerociclib for 24 hours compared to vehicle controls. G1T38 reduces RB phosphorylation within 1 hour post-treatment, reaching near-complete inhibition by 16 hours. G1T38 robustly inhibits proliferation in various tumor cell lines, including breast, melanoma, leukemia, and lymphoma, with EC50s as low as 23 nM. Within the CDK family, Lerociclib is least selective against CDK9/cyclin T, showing ~30-fold selectivity between CDK4/cyclin D1 and CDK9/cyclin T at the biochemical IC50.

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

Cyclin dependent kinase, CDK, CDK2/cyclinE, cdk2/cyclin A, CDK2/CyclinA, CDK1/cyclinB1, Cdk5/p25, CDK4/CyclinD1, Cdk4/cyclin D1, cdk6/cyclin D3, CDK6/CyclinD3, CDK5/p35, CDK7/Cyclin H/MAT1, CDK9/Cyclin T, CDK9/CyclinT, inhibit, Inhibitor, Lerociclib, Lerociclib Dihydrochloride, Lerociclib dihydrochloride, G1T38, G1T38 Dihydrochloride, G1T38 dihydrochloride

Compound Identifiers

PubChem CID

129896913