Cdk4/6 Inhibitor IV

SKU: orb1220166

Description

Cdk4/6 inhibitor IV is a cell-permeable triaminopyrimidine that reversibly blocks Cdk4/cyclin D1 and Cdk6/cyclin D1 activity with IC50 values of 1.5 and 5.6 μM, respectively.It demonstrates potent selectivity for Cdk4/6 over Cdk5/p35, v-abl, c-met, IGF-1R, insulin receptor, Cdk2/cyclin A, Cdk2/cyclin E, Cdk4/cyclin D2, Cdk6/cyclin D2, and Cdk1/cyclin B (IC50s = > 10-100 μM).At 5-10 μM, this compound blocks retinoblastoma protein phosphorylation at Ser780 and Ser795, inducing cell cycle arrest in the G1 phase and apoptosis in asynchronous cell lines.In mice bearing human HCT116 colon carcinoma xenografts, 30 mg/kg, i.p. Cdk/6 inhibitor IV suppressed tumor growth after 29 days of treatment.

Research Area

Pharmacology & Drug Discovery

Key Properties

• CAS Number: 359886-84-3
• MW: 456.6
• Purity: >98% (HPLC)
• Formula: C₂₇H₃₂N₆O
• SMILES: CCNC1=NC(NC2=CC=C(N(CC3=CC=CC=C3)C=C4)C4=C2)=NC(N[C@H]5CC[C@H](O)CC5)=C1
• Solubility: DMF: 30 mg/ml;DMSO: 30 mg/ml;DMSO:PBS(pH 7.2) (1:4): 0.2 mg/ml;Ethanol: 1 mg/ml

Bioactivity

• In Vivo:
  GP-82996 (30 mg/kg, i.p. for 29 days) shows smaller final tumor volume compared with vehicle control in mouse xenograft models. Animal model: 19-21 g female BALB/c nu/nu mice xenograft model (HCT116 tumors volume = 100 mm3). Dosage: 30 mg/kg. Administration: i.p. every 12 hours for 29 days. Result: Showed smaller final tumor volume compared with vehicle control in mouse xenograft models.
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• In Vitro:
  GP-82996 (5, 10 μM; 24 hours) induces G1 arrest and G0-G1/S ratio increase in U2OS (p16 negative) and MRC-5 (p16 positive) cells. GP-82996 (5, 10 μM; 24 hours) reduces hyperphosphorylation of pRb, but has no changes in the levels of CDK4 in U2OS, MRC-5 cells. GP-82996 (5, 10 μM; 48 hours) induces aooptosis in 83% of U2OS cells in concentration of 10 μM. GP-82996 (0.1-40 μM; 24, 48, 72 hours) inhibits the cell proliferation of A549, H358, SKLU-1, H23, PC14 cells with IC50 values of 72 h are 4-7 μM. GP-82996 (3, 5, 10 μM; 48 hours) induces G1 arrest in A549 and H23 cells. GP-82996 ((1, 3, 5, 10 μM; 72 hours) enhances Paclitaxel sensitivity in KRAS mutation-bearing lung cancer cells (A549, SKLU-1, H23 cells). GP-82996 (10 μM; 72 hours) combined with Paclitaxel (3 nM; 72 hours) increases the apoptosis of A549 and H23 cells.
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Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only