1. Cell Cycle/DNA Damage
  2. CDK

LEE011 hydrochloride (Synonyms: Ribociclib hydrochloride)

Cat. No.: HY-15777A
Handling Instructions

LEE011 hydrochloride is a highly specific CDK4/6 inhibitor with IC50 values of 10 nM and 39 nM, respectively, and is over 1,000-fold less potent against the cyclin B/CDK1 complex.

For research use only. We do not sell to patients.
LEE011 hydrochloride Chemical Structure

LEE011 hydrochloride Chemical Structure

CAS No. : 1211443-80-9

Size Price Stock Quantity
10 mM * 1 mL in DMSO $66 In-stock
5 mg $60 In-stock
10 mg $80 In-stock
50 mg $150 In-stock
100 mg $250 In-stock
200 mg   Get quote  
500 mg   Get quote  

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Other Forms of LEE011 hydrochloride:

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  • Biological Activity

  • Protocol

  • Technical Information

  • References

Description

LEE011 hydrochloride is a highly specific CDK4/6 inhibitor with IC50 values of 10 nM and 39 nM, respectively, and is over 1,000-fold less potent against the cyclin B/CDK1 complex.

IC50 & Target

IC50: 10/39 nM (CDK4/6)[1]

In Vitro

Treating a panel of 17 neuroblastoma cell lines with LEE011 (Ribociclib) across a four-log dose range (10 to 10,000 nM). Treatment with LEE011 significantly inhibits substrate adherent growth relative to the control in 12 of the 17 neuroblastoma cell lines examined (mean IC50=306±68 nM, considering sensitive lines only, where sensitivity is defined as an IC50 of less than 1 μM. LEE011 treatment of two neuroblastoma cell lines (BE2C and IMR5) with demonstrated sensitivity to CDK4/6 inhibition results in a dose-dependent accumulation of cells in the G0/G1 phase of the cell cycle. This G0/G1 arrest becomes significant at LEE011 concentrations of 100 nM (p=0.007) and 250 nM (p=0.01), respectively[2].

In Vivo

CB17 immunodeficient mice bearing BE2C, NB-1643 (MYCN amplified, sensitive in vitro), or EBC1 (non-amplified, resistant in vitro) xenografts are treated once daily for 21 days with LEE011 (200 mg/kg) or with a vehicle control. This dosing strategy is well tolerated, as no weight loss or other signs of toxicity are observed in any of the xenograft models. Tumor growth is significantly delayed throughout the 21 days of treatment in mice harboring the BE2C or 1643 xenografts (both, p<0.0001), although growth resumed post-treatment[2].

Clinical Trial
NCT Number Sponsor Condition Start Date Phase
NCT02632045 Kevin Kalinsky|Novartis Pharmaceuticals|Columbia University Metastatic Breast Cancer|Breast Carcinoma March 2016 Phase 2
NCT02934568 Novartis Pharmaceuticals|Novartis Continued Access to Study Treatment(s), Cancers With a Mass, Bulky Tumor, Nodule, Lump, Advanced Cancer, Advanced Solid Tumors, Advanced Solid Malignancies December 15, 2016 Phase 2
NCT02420691 M.D. Anderson Cancer Center|Novartis Gastrointestinal Cancer August 2015 Phase 2
NCT02187783 Novartis Pharmaceuticals|Novartis Tumors With CDK4/6 Pathway Activation August 25, 2014 Phase 2
NCT01237236 Novartis Pharmaceuticals|Novartis Advanced Solid Tumor|Lymphomas December 21, 2010 Phase 1
NCT03070301 Memorial Sloan Kettering Cancer Center|Novartis|Dana-Farber Cancer Institute|M.D. Anderson Cancer Center Neuroendocrine Tumors February 27, 2017 Phase 2
NCT02388620 Novartis Pharmaceuticals|Novartis Normal Hepatic Function|Impaired Hepatic Function March 25, 2015 Phase 1
NCT02343172 Novartis Pharmaceuticals|Novartis Liposarcoma March 14, 2015 Phase 1|Phase 2
NCT02429089 Cliniques universitaires Saint-Luc- Université Catholique de Louvain Squamous Cell Carcinoma of the Head and Neck April 2015 Phase 1
NCT02431481 Novartis Pharmaceuticals|Novartis Normal Renal Function|Impaired Renal Function October 23, 2015 Phase 1
NCT01898845 Novartis Pharmaceuticals|Novartis Advanced Solid Tumors May 2013 Phase 1
NCT01777776 Array BioPharma Locally Advanced Metastatic BRAF Mutant Melanoma July 2013 Phase 1|Phase 2
NCT01872260 Novartis Pharmaceuticals|Novartis Breast Cancer October 22, 2013 Phase 1
NCT02292550 Novartis Pharmaceuticals|Novartis Non-small Cell Lung Cancer May 14, 2015 Phase 1|Phase 2
NCT01857193 Novartis Pharmaceuticals|Novartis Breast Cancer September 6, 2013 Phase 1
NCT02300987 Novartis Pharmaceuticals|Novartis Teratoma February 26, 2015 Phase 2
NCT01919229 Novartis Pharmaceuticals|Novartis Early Breast Cancer October 2013 Phase 2
NCT02985125 Georgetown University|Novartis|University of Texas Southwestern Medical Center|Cedars-Sinai Medical Center|Virginia Mason Hospital/Medical Center Metastatic Pancreatic Adenocarcinoma May 4, 2017 Phase 1|Phase 2
NCT02088684 Novartis Pharmaceuticals|Novartis Breast Cancer May 2014 Phase 1|Phase 2
NCT01958021 Novartis Pharmaceuticals|Novartis Advanced, Metastatic Breast Cancer December 17, 2013 Phase 3
NCT02734615 Novartis Pharmaceuticals|Novartis Advanced or Metastatic ER+ Breast Cancer April 27, 2016 Phase 1
NCT01747876 Novartis Pharmaceuticals|Novartis Malignant Rhabdoid Tumors (MRT), Neuroblastoma May 28, 2013 Phase 1
NCT02333370 Novartis Pharmaceuticals|Novartis Hormone Receptor Positive, HER2-negative, Advanced Breast Cancer February 4, 2015 Phase 1
NCT02154776 Novartis Pharmaceuticals|Novartis Advanced or Metastatic Breast Cancer June 27, 2014 Phase 1
NCT01781572 Array BioPharma Locally Advanced or Metastatic NRAS Mutant Melanoma June 2013 Phase 1|Phase 2
NCT02941926 Novartis Pharmaceuticals|Novartis Breast Cancer November 30, 2016 Phase 3
NCT02599363 Abramson Cancer Center of the University of Pennsylvania Advanced Breast Cancer January 2016 Phase 1
NCT02370706 Novartis Pharmaceuticals|Novartis Myelofibrosis May 21, 2015 Phase 1
NCT02524119 University of Texas Southwestern Medical Center|Novartis Pharmaceuticals Hepatocellular Carcinoma April 2016 Phase 2
NCT02278120 Novartis Pharmaceuticals|Novartis Advanced, Metastatic Breast Cancer November 21, 2014 Phase 3
NCT01543698 Array BioPharma Solid Tumors Harboring a BRAF V600 Mutation May 2012 Phase 1|Phase 2
NCT02159066 Array BioPharma Melanoma July 2014 Phase 2
NCT03096912 Assaf-Harofeh Medical Center Liposarcomas, Dedifferentiated|Liposarcoma - Well Differentiated|Liposarcoma; Mixed Type|Soft-Tissue Sarcoma July 2016 Phase 2
NCT02754011 UNICANCER|Novartis Breast Cancer January 2017 Phase 1
NCT02933736 St. Joseph's Hospital and Medical Center, Phoenix|Novartis Glioblastoma Multiforme|Meningioma October 2016 Early Phase 1
NCT02345824 University of Virginia|Novartis Pharmaceuticals Glioblastoma|Glioma March 2016 Phase 1
NCT02571829 Hadassah Medical Organization Liposarcoma|Soft Tissue Sarcoma May 2016 Phase 2
NCT02712723 University of Kansas Medical Center|Novartis Pharmaceuticals Breast Cancer February 2016 Phase 2
NCT03008408 M.D. Anderson Cancer Center|Novartis Malignant Neoplasms of Female Genital Organs|Endometrial Carcinoma September 2017 Phase 2
NCT03114527 Fox Chase Cancer Center Soft Tissue Sarcoma September 2017 Phase 2
NCT03056833 University of Michigan Cancer Center Ovarian Cancer|Fallopian Tube Cancer|Peritoneal Carcinoma June 10, 2017 Phase 1
NCT02555189 Sidney Kimmel Cancer Center at Thomas Jefferson University|Novartis|Prostate Cancer Clinical Trials Consortium|Thomas Jefferson University Hormone-Resistant Prostate Cancer|Metastatic Prostate Carcinoma|Prostate Carcinoma Metastatic in the Bone|Stage IV Prostate Cancer December 2015 Phase 1|Phase 2
NCT03050398 Novartis Pharmaceuticals|Novartis Breast Cancer December 1, 2016 Phase 3
NCT03078751 Novartis Pharmaceuticals|Novartis Breast Cancer June 20, 2017 Phase 3
NCT03081234 Novartis Pharmaceuticals|Novartis Breast Cancer June 9, 2017 Phase 3
NCT03009201 OHSU Knight Cancer Institute|National Cancer Institute (NCI) Metastatic Angiosarcoma|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 January 2017 Phase 1
NCT02414724 Roswell Park Cancer Institute|National Cancer Institute (NCI)|Novartis Lymphoma|Solid Neoplasm May 2015 Phase 1
NCT03090165 Ruth O'Regan, M.D.|Novartis|Big Ten Cancer Research Consortium Triple Negative Breast Cancer March 2, 2017 Phase 1|Phase 2
NCT02607124 Children's Hospital Medical Center, Cincinnati|Novartis High Grade Glioma|Diffuse Intrinsic Pontine Glioma|Bithalamic High Grade Glioma April 2016 Phase 1|Phase 2
NCT03179956 Fox Chase Cancer Center Squamous Cell Carcinoma of the Head and Neck September 2017 Early Phase 1
NCT02586675 H. Lee Moffitt Cancer Center and Research Institute|Novartis Breast Cancer|Breast Cancer - Female|Breast Cancer - Male February 15, 2016 Phase 1
NCT02657928 Mayo Clinic|National Cancer Institute (NCI) Estrogen Receptor Positive|Postmenopausal|Recurrent Fallopian Tube Carcinoma|Recurrent Ovarian Carcinoma|Recurrent Primary Peritoneal Carcinoma|Recurrent Uterine Corpus Carcinoma July 8, 2016 Phase 2
NCT02732119 Novartis Pharmaceuticals|Novartis Breast Cancer June 14, 2016 Phase 1|Phase 2
NCT03096847 Novartis Pharmaceuticals|Novartis Advanced Metastatic Breast Cancer October 24, 2016 Phase 3
NCT02657343 Dana-Farber Cancer Institute|Novartis Breast Cancer March 9, 2016 Phase 1|Phase 2
NCT02422615 Novartis Pharmaceuticals|Novartis Breast Neoplasms|Breast Diseases|Neoplasms|Neoplasms by Site|Fulvestrant|Antineoplastic Agents|Antineoplastic Agents, Hormonal|Estrogen Receptor Antagonists|Hormone Antagonists|Hormones, Hormone Substitutes, and Hormone Antagonists|Molecular Mechanisms of Pharmacological Action|Pharmacologic Actions|Therapeutic Use June 9, 2015 Phase 3
NCT02703571 Novartis Pharmaceuticals|Novartis Solid Tumors|Pancreatic Cancer|Colorectal Cancer June 30, 2016 Phase 1|Phase 2
NCT02494921 Rahul Aggarwal|University of California, San Francisco Prostate Cancer September 2015 Phase 1|Phase 2
NCT02608216 University of Pennsylvania Breast Neoplasm|Metastatic Breast Cancer|Rb+ Breast Cancer November 2015 Phase 1
NCT02780128 Yael P Mosse|Novartis Pharmaceuticals|Foundation Medicine|Children's Hospital of Philadelphia Neuroblastoma|Cancer July 2016 Phase 1
NCT02813135 Gustave Roussy, Cancer Campus, Grand Paris|National Cancer Institute, France Children, Adolescents and Young Adults With Refractory or Recurrent Malignancies June 2016 Phase 1|Phase 2
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References
Preparing Stock Solutions
Concentration Volume (DMSO) Mass 1 mg 5 mg 10 mg
1 mM 2.1231 mL 10.6157 mL 21.2314 mL
5 mM 0.4246 mL 2.1231 mL 4.2463 mL
10 mM 0.2123 mL 1.0616 mL 2.1231 mL
Cell Assay
[2]

LEE011 (Ribociclib) is dissolved in DMSO and stored, and then diluted with appropriate media before use[2].

Cells are grown for 24 hours in 35 mm plates, treated with 500 nM LEE011 for 6 days, and then fixed and stained overnight. Cells are then imaged for SA-β-gal using an Axio Observer D.1 phase contrast microscope. The percentage of SA-β-gal positive cells is determined by counting the number of positive cells present in three separate microscope frames, and then normalizing to the control. To assess apoptotic activity, cells are plated in triplicate in 96 well plates, treated with LEE011, and assayed for caspase 3/7 activation 16 hours after treatment with Caspase-Glo 3/7. Cells treated with SN-38 are used as a positive control[2]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration
[2]

LEE011 (Ribociclib) is dissolved in 0.5 % methylcellulose (Mice)[2].

Mice[2]
The BE2C, NB-1643, or EBC1 cell line-derived xenografts are implanted subcutaneously into the right flank of CB17 SCID-/- mice. Animals bearing engrafted tumors of 200-600 mm3 are then randomized to oral treatment with 200 mg/kg LEE011 in 0.5 % methylcellulose (n=10) or vehicle (n=10) daily for a total of 21 days. Tumor burden is determined periodically throughout treatment according to the formula (π/6)×d2, where d represents the mean tumor diameter obtained by caliper measurement. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

References
Molecular Weight

471.0

Formula

C₂₃H₃₁ClN₈O

CAS No.

1211443-80-9

Storage

Please store the product under the recommended conditions in the Certificate of Analysis.

Shipping

Room temperature in continental US; may vary elsewhere

Solvent & Solubility

10 mM in DMSO

LEE011 salt is dissolved in 0.5% methylcellulose[3].

* "<1 mg/mL" means slightly soluble or insoluble. "≥" means soluble, but saturation unknown.

References

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LEE011 hydrochloride
Cat. No.:
HY-15777A
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