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Purity: ≥98%
Ribociclib succinate (LEE011, NVP-LEE-011; LEE-011, NVP-LEE011; Kisqali), the succinate salt of Ribociclib, is a CDK4/6 (cyclin-dependent kinase) inhibitor (IC50s = 10 nM and 39 nM) approved in March 2017 by FDA for the treatment of breast cancer.
| Targets |
CDK4 (IC50 = 10 nM); CDK6 (IC50 = 30 nM)
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| Enzyme Assay |
Ribociclib, a powerful, oral, and highly selective inhibitor of CDK4/6 (cyclin-dependent kinase), with IC50s of 10 nM and 39 nM, respectively, was previously known as LEE011, NVP-LEE011; trade name: Kisqali. In March 2017, the FDA approved Ribociclib as a treatment for postmenopausal women who had an advanced form of breast cancer. Ribociclib works by reducing the levels of phosphorylated FOXM1 and RB. Out of 17 human neuroblastoma cell lines tested, 12 showed sensitivity to ribofacilb treatment (mean IC50=306±68 NM). By stopping the G0-G1 cell cycle, ribociclib treatment may significantly reduce the rate of cell proliferation. Treatment with LEE011 could markedly inhibit cell proliferation in 12 out of 17 human neuroblastoma-derived cell lines.
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| Cell Assay |
The Xcelligence Real-Time Cell Electronic Sensing system is used to plate a panel of neuroblastoma cell lines in triplicate. The cell lines were chosen based on previous evidence of substrate adherent growth. The cells are then treated with an inhibitor within a four-log dose range or with a dimethyl sulfoxide (DMSO) control 24 hours later. After approximately 100 hours of continuous monitoring of cell indexes, the following IC50 values are calculated: Plotting the cell index against time yields growth curves, which are then normalized to the cell index at treatment onset for a baseline cell index of 1. This is followed by calculating the area under the normalized growth curve from the time of treatment to 96 hours posttreatment using a baseline area of 1 (the cell index at the time of treatment). The data are analyzed using a nonlinear log inhibitor versus normalized response function after areas are normalized to the DMSO control. At least one repetition of each experiment is conducted.
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| Animal Protocol |
Mice: The xenografts derived from BE2C, NB-1643, or EBC1 cell lines are subcutaneously implanted into the right flank of CB17 SCID-/-mice. Then, for a total of 21 days, animals with engrafted tumors measuring 200–600 mm3 are randomly assigned to receive oral treatment with 200 mg/kg Ribociclib in 0.5% methylcellulose (n = 10) or vehicle (n = 10). Throughout the course of treatment, the tumor burden is calculated on a regular basis using the formula (π/6)×d2, where d is the mean tumor diameter measured with a caliper.
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| Additional Infomation |
See also: Ribociclib (has active moiety); Letrozole; ribociclib succinate (component of).
Drug Indication Kisqali is indicated for the treatment of women with hormone receptor (HR)âpositive, human epidermal growth factor receptor 2 (HER2)ânegative locally advanced or metastatic breast cancer in combination with an aromatase inhibitor or fulvestrant as initial endocrine-based therapy, or in women who have received prior endocrine therapy. In preâ or perimenopausal women, the endocrine therapy should be combined with a luteinising hormoneâreleasing hormone (LHRH) agonist. Treatment of breast cancer |
| Molecular Formula |
C27H36N8O5
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| Molecular Weight |
552.64
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| Exact Mass |
552.28
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| Elemental Analysis |
C, 58.68; H, 6.57; N, 20.28; O, 14.48
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| CAS # |
1374639-75-4
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| Related CAS # |
Ribociclib;1211441-98-3;Ribociclib hydrochloride;1211443-80-9;Ribociclib-d6 hydrochloride;Ribociclib succinate hydrate;1374639-79-8
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| PubChem CID |
57334219
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| Appearance |
Light yellow to yellow solid powder
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
11
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
40
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| Complexity |
728
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C(C1=C([H])C2=C([H])N=C(N([H])C3C([H])=C([H])C(=C([H])N=3)N3C([H])([H])C([H])([H])N([H])C([H])([H])C3([H])[H])N=C2N1C1([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H])N(C([H])([H])[H])C([H])([H])[H].O([H])C(C([H])([H])C([H])([H])C(=O)O[H])=O
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| InChi Key |
NHANOMFABJQAAH-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C23H30N8O.C4H6O4/c1-29(2)22(32)19-13-16-14-26-23(28-21(16)31(19)17-5-3-4-6-17)27-20-8-7-18(15-25-20)30-11-9-24-10-12-30;5-3(6)1-2-4(7)8/h7-8,13-15,17,24H,3-6,9-12H2,1-2H3,(H,25,26,27,28);1-2H2,(H,5,6)(H,7,8)
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| Chemical Name |
butanedioic acid;7-cyclopentyl-N,N-dimethyl-2-[(5-piperazin-1-ylpyridin-2-yl)amino]pyrrolo[2,3-d]pyrimidine-6-carboxamide
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| Synonyms |
LEE011 succinate; LEE-011 succinate; LEE 011 succinate; trade name: Kisqali; LEE011 succinate; LEE-011 succinate; LEE011-BBA; Birociclib; 7-Cyclopentyl-N,N-dimethyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide succinate; UNII-BG7HLX2919;
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 3.12 mg/mL (5.65 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication (<60°C).
(Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8095 mL | 9.0475 mL | 18.0950 mL | |
| 5 mM | 0.3619 mL | 1.8095 mL | 3.6190 mL | |
| 10 mM | 0.1809 mL | 0.9047 mL | 1.8095 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Pharmacologic inhibition of CDK4/6 suppresses neuroblastoma growthin vitro.(A)The growth of 12 of 17 neuroblastoma cell lines was significantly impaired in response to CDK4/6 inhibition with LEE011 (mean IC50= 306 ± 68 nM, sensitive lines only). Data are plotted (and tabulated) as the best fit IC50per log(inhibitor) vs. normalized response analysis (GraphPad); upper and lower bars represent 95 % confidence levels.(B)Dose-dependent decreases in pRBS780accompany growth suppression in sensitive lines and are indicative of on- target activity.Clin Cancer Res.2013 Nov 15;19(22):6173-82. |
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 Growth suppression via CDK4/6 inhibition is mediated by cell cycle arrest and senescence. Neuroblastoma cell lines with demonstrated sensitivity or resistance to LEE011 were analyzed for cell cycle arrest and senescence associated β-galactosidase (SA-β-gal) activity.(A)A significant G1arrest accompanied by reductions in the fraction of cells in S phase and G2/M was observed in sensitive lines only.(B)Representative cell cycle histograms of a sensitive and resistant cell line.(C)Down-regulation of FOXM1 mRNA and(D)protein was observed in sensitive lines and was associated with(E)the induction of a senescent phenotype.Clin Cancer Res.2013 Nov 15;19(22):6173-82. |
 Inhibition of CDK4/6 suppresses neuroblastoma growthin vivo.(A)Mice with subcutaneously implanted xenografts were treated daily with 200 mg/kg LEE011 or with a vehicle for 21 days. In two of three neuroblastoma xenograft models, treatment with LEE011 significantly reduced tumor burden in comparison to vehicle, as determined by linear mixed effects analysis (BE2C, p<0.0001; 1643, p <0.0001; EBC1 p = 0.51).(B)The reduction in tumor proliferation observed in sensitive lines was confirmed by Ki67 staining of resected xenografts, and inhibition of CDK4/6 activity was confirmed by(C)immunohistochemical staining and western blot for pRBS780.Clin Cancer Res.2013 Nov 15;19(22):6173-82. |
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