生物活性

• 描述CDK4/6, forming a complex with its partner Cyclin D1/2/3, can mediate the phosphorylation of Rb in G1 cell cycle, as well as stimulating the synthesis cyclin E and D-type cyclins controlled by extracellular mitogens. LEE011 Hydrochloride is the hydrochloride form of LEE011. LEE011 (Ribociclib) is an orally bioavailable dual CDK4/6 inhibitor with IC50 value of 10nM and 40nM, respectively. Treatment of LEE011 (0.25-10uM) can cause decrease in pRB-S780 accompany growth suppression in BE2C, EBC1, IMR5 and SKNAS neuroblastoma cell lines by a dose-dependent manner. 100-250nM of LEE011 can cause accumulation of G0/G1 phase of the cell cycle and cellular senescence with decreased FOXM1 in BE2C and IMR5 cells. Once daily for 21 days with 200 mg/kg LEE011 can suppresse neuroblastoma growth in mice with subcutaneously implanted BE2C or 1643 xenografts. There are currently 16 active clinical trials with LEE011 as single agent or in combination with other drugs for treatment for melanoma, breast cancer, neuroblastoma, malignant rhabdoid and lymphomas.

• 动物研究
  剂量	Mice: 200 mg/kg[2] (p.o.)
  给药途径	p.o.
  动物药代数据	Animal Rats[3] Monkeys[3] Dose 50 mg/kg 2 mg/kg Administration p.o. p.o. F 0.166 T1/2 4.69 h Tmax 0.24 h (plasma) 1 h (milk) 2 - 4 h CL 35.3 ml/min/kg Cmax 3.45 μM (plasma) 12.6 μM (milk)

• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT03009201	Metastatic Angiosarcoma ... more >> Metastatic Epithelioid Sarcoma Metastatic Fibrosarcoma Metastatic Leiomyosarcoma Metastatic Liposarcoma Metastatic Malignant Peripheral Nerve Sheath Tumor Metastatic Synovial Sarcoma Metastatic Undifferentiated Pleomorphic Sarcoma Myxofibrosarcoma Pleomorphic Rhabdomyosarcoma Stage III Soft Tissue Sarcoma Stage IV Soft Tissue Sarcoma Undifferentiated (Embryonal) Sarcoma Collapse <<	Phase 1	Recruiting	December 2020	United States, Oregon ... more >> OHSU Knight Cancer Institute Recruiting Portland, Oregon, United States, 97239 Contact: Laura Carter    503-418-9354    cartela@ohsu.edu    Contact: Phil Norr    503-494-0825    norr@ohsu.edu    Principal Investigator: Lara E. Davis Collapse <<
  NCT03237390	Advanced Malignant Solid Neopl... more >>asm Metastatic Malignant Solid Neoplasm Collapse <<	Phase 1	Recruiting	August 9, 2020	United States, Arizona ... more >> Mayo Clinic Hospital Recruiting Phoenix, Arizona, United States, 85054 Contact: Clinical Trials Referral Office    855-776-0015       Principal Investigator: Ramesh K. Ramanathan          United States, Florida Mayo Clinic in Florida Recruiting Jacksonville, Florida, United States, 32224-9980 Contact: Clinical Trials Referral Office    855-776-0015       Principal Investigator: Kabir Mody          United States, Minnesota Mayo Clinic Recruiting Rochester, Minnesota, United States, 55905 Contact: Clinical Trials Referral Office    855-776-0015       Principal Investigator: Alex A. Adjei Collapse <<
  NCT02414724	Lymphoma Soli... more >>d Neoplasm Collapse <<	Phase 1	Terminated(PI left institute)	-	United States, New York ... more >> Roswell Park Cancer Institute Buffalo, New York, United States, 14263 Collapse <<

• 更多
• 参考文献

• [1] Tripathy D, Bardia A, Sellers WR. Ribociclib (LEE011): Mechanism of Action and Clinical Impact of This Selective Cyclin-Dependent Kinase 4/6 Inhibitor in Various Solid Tumors. Clin Cancer Res. 2017 Jul 1;23(13):3251-3262.

  [2] Rader J, Russell MR, et al. Dual CDK4/CDK6 inhibition induces cell-cycle arrest and senescence in neuroblastoma. Clin Cancer Res. 2013 Nov 15;19(22):6173-82.

  [3] LEE011