Ribociclib Free Base | LEE-011 | CAS#1211441-98-3 | 1211443-80-9 | CDK inhibitor

MedKoo Cat#: 205513 | Name: Ribociclib Free Base

Description:

WARNING: This product is for research use only, not for human or veterinary use.

Ribociclib, also known as LEE011, is an orally available cyclin-dependent kinase (CDK) inhibitor targeting cyclin D1/CDK4 and cyclin D3/CDK6 cell cycle pathway, with potential antineoplastic activity. LEE011 specifically inhibits CDK4 and 6, thereby inhibiting retinoblastoma (Rb) protein phosphorylation.

Chemical Structure

Ribociclib Free Base

CAS#1211441-98-3 (free base)

Theoretical Analysis

MedKoo Cat#: 205513

Name: Ribociclib Free Base

CAS#: 1211441-98-3 (free base)

Chemical Formula: C23H30N8O

Exact Mass: 434.2543

Molecular Weight: 434.54

Elemental Analysis: C, 63.57; H, 6.96; N, 25.79; O, 3.68

Price and Availability

Size	Price	Availability
25mg	USD 90.00	Ready to ship
50mg	USD 150.00	Ready to ship
100mg	USD 250.00	Ready to ship
200mg	USD 450.00	Ready to ship
500mg	USD 950.00	Ready to ship
1g	USD 1,650.00	Ready to ship

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Related CAS #

1211441-98-3 (free base) 1211443-80-9 (HCl) 1374639-75-4 (succinate)

Synonym

LEE011; LEE-011. LEE 011; Ribociclib; Kisqali.

IUPAC/Chemical Name

7-cyclopentyl-N,N-dimethyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide

InChi Key

RHXHGRAEPCAFML-UHFFFAOYSA-N

InChi Code

InChI=1S/C23H30N8O/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/h7-8,13-15,17,24H,3-6,9-12H2,1-2H3,(H,25,26,27,28)

SMILES Code

O=C(C1=CC2=CN=C(NC3=NC=C(N4CCNCC4)C=C3)N=C2N1C5CCCC5)N(C)C

Appearance

Yellow solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO, not in water

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Related CAS# 1211441-98-3 (Ribociclib free base) 1211443-80-9 (Ribociclib hydrochloride) 1374639-75-4 (Ribociclib succinate)

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#XPR61208

View CoA: previous batch, Lot#TZC50723

QC Data

View QC data: previous batch, Lot#TZC50723

View QC data: current batch, Lot# XPR61208

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Ribociclib is a highly specific CDK4/6 inhibitor with IC50 values of 10 nM and 39 nM, respectively. It inhibits Rb phosphorylation, which prevents CDK-mediated G1-S phase transition, thereby arresting the cell cycle in the G1 phase, suppressing DNA synthesis and inhibiting cancer cell growth.

In vitro activity:

Ribociclib induces apoptosis of renal cell carcinoma (RCC) cell. The combination of ribociclib with chemotherapeutic or immunotherapeutic agents is synergistic in RCC cell lines. Ribociclib demonstrates selective anti-RCC activity by sparing normal kidney cells and fibroblast cells. Ribociclib remarkably inhibits phosphorylation of Rb at various sites, leading to the suppression of transcription of E2F target genes in RCC cells. Reference: Biomed Res Int. 2020; 2020: 9525207. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7306082/

In vivo activity:

Treatment of mice tumos with the combination of ribociclib and gemcitabine was well tolerated, slowed tumor progression and metastatic spread, and increased survival. The findings in both mouse and human patient-derived orthotopic xenograft models suggest that ribociclib and gemcitabine combination therapy warrants further investigation as a treatment strategy for children with group3 medulloblastoma. Reference: Mol Cancer Ther. 2022 Aug 2;21(8):1306-1317. https://pubmed.ncbi.nlm.nih.gov/35709750/

	Solvent	mg/mL	mM
Solubility
	DMSO	6.9	15.97

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 434.54 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Chen D, Sun X, Zhang X, Cao J. Inhibition of the CDK4/6-Cyclin D-Rb Pathway by Ribociclib Augments Chemotherapy and Immunotherapy in Renal Cell Carcinoma. Biomed Res Int. 2020 Jun 11;2020:9525207. doi: 10.1155/2020/9525207. PMID: 32626773; PMCID: PMC7306082. 2. Kim S, Tiedt R, Loo A, Horn T, Delach S, Kovats S, Haas K, Engstler BS, Cao A, Pinzon-Ortiz M, Mulford I, Acker MG, Chopra R, Brain C, di Tomaso E, Sellers WR, Caponigro G. The potent and selective cyclin-dependent kinases 4 and 6 inhibitor ribociclib (LEE011) is a versatile combination partner in preclinical cancer models. Oncotarget. 2018 Oct 16;9(81):35226-35240. doi: 10.18632/oncotarget.26215. Erratum in: Oncotarget. 2020 Apr 07;11(14):1289. PMID: 30443290; PMCID: PMC6219668. 3. Malorni L, Bianchini G, Caputo R, Zambelli A, Puglisi F, Bianchi GV, Del Mastro L, Paris I, Montemurro F, Allegrini G, Colleoni M, Tamberi S, Zamagni C, Cazzaniga ME, Orditura M, Guarneri V, Castelletti D, Benelli M, Di Marino M, Arpino G, De Laurentiis M. Serum thymidine kinase activity in patients with HR-positive/HER2-negative advanced breast cancer treated with ribociclib plus letrozole: Results from the prospective BioItaLEE trial. Eur J Cancer. 2023 Jun;186:1-11. doi: 10.1016/j.ejca.2023.03.001. Epub 2023 Mar 8. PMID: 37003098. 4. Pribnow A, Jonchere B, Liu J, Smith KS, Campagne O, Xu K, Robinson S, Patel Y, Onar-Thomas A, Wu G, Stewart CF, Northcott PA, Yu J, Robinson GW, Roussel MF. Combination of Ribociclib and Gemcitabine for the Treatment of Medulloblastoma. Mol Cancer Ther. 2022 Aug 2;21(8):1306-1317. doi: 10.1158/1535-7163.MCT-21-0598. PMID: 35709750; PMCID: PMC9578677.

In vitro protocol:

In vivo protocol:

1. Malorni L, Bianchini G, Caputo R, Zambelli A, Puglisi F, Bianchi GV, Del Mastro L, Paris I, Montemurro F, Allegrini G, Colleoni M, Tamberi S, Zamagni C, Cazzaniga ME, Orditura M, Guarneri V, Castelletti D, Benelli M, Di Marino M, Arpino G, De Laurentiis M. Serum thymidine kinase activity in patients with HR-positive/HER2-negative advanced breast cancer treated with ribociclib plus letrozole: Results from the prospective BioItaLEE trial. Eur J Cancer. 2023 Jun;186:1-11. doi: 10.1016/j.ejca.2023.03.001. Epub 2023 Mar 8. PMID: 37003098. 2. Pribnow A, Jonchere B, Liu J, Smith KS, Campagne O, Xu K, Robinson S, Patel Y, Onar-Thomas A, Wu G, Stewart CF, Northcott PA, Yu J, Robinson GW, Roussel MF. Combination of Ribociclib and Gemcitabine for the Treatment of Medulloblastoma. Mol Cancer Ther. 2022 Aug 2;21(8):1306-1317. doi: 10.1158/1535-7163.MCT-21-0598. PMID: 35709750; PMCID: PMC9578677.

1: Patil PH, Desai MP, Anand VSK, Ray R, Shenoy GG, Dengale SJ, Bhat K, Jagadish PC. A Molecular Dynamic Simulation, Structural Analysis, and Ex Vivo Insights into the P-glycoprotein-Mediated Interactions of Dietary Polyphenols with Cyclin-dependent Kinase Inhibitors: A Potential Strategy to Counteract Drug Efflux. Curr Med Chem. 2024 Sep 12. doi: 10.2174/0109298673319832240829164046. Epub ahead of print. PMID: 39279123. 2: Hua M, Xiong F, Chong S, Zhang Z, Liu Q, Hou J, Zhang Z, Gu Z, Cui X, Cui Y, Xu L, Xiang Q. Abemaciclib increases the risk of venous thromboembolism in breast cancer: Integrate meta-analysis, pharmacovigilance database analysis, and in vitro validation. Cancer Treat Rev. 2024 Sep 7;130:102827. doi: 10.1016/j.ctrv.2024.102827. Epub ahead of print. PMID: 39278067. 3: Zhao Q, Jiang M, Liu J, Zhang M, He M, Zhou S, Wang J, Mo H, Lan B, Yuan P, Zhang P, Ma F, Li Q, Xu B. Clinical benefit and safety profile of cross-line therapy with CDK4/6 inhibitors: a retrospective study of HR+/HER2- advanced breast cancer. Cancer Biol Med. 2024 Sep 11:j.issn.2095-3941.2024.0204. doi: 10.20892/j.issn.2095-3941.2024.0204. Epub ahead of print. PMID: 39267478. 4: Correction to: Initial ribociclib plus endocrine therapy for HR+/HER2- advanced breast cancer in pre- and postmenopausal Chinese women: Primary results from a phase 2 randomized study. Cancer Med. 2024 Sep;13(17):e70233. doi: 10.1002/cam4.70233. Erratum for: Cancer Med. 2024 Aug;13(15):e7408. doi: 10.1002/cam4.7408. PMID: 39275877; PMCID: PMC11399713. 5: Yang P, Zhang H, Wu M, Zhao F, Wang M, Zhao J, Zhao Y. Dose reduction and discontinuation due to the combination of CDK4/6 inhibitors and endocrine drugs: a systematic review and meta-analysis. Eur J Clin Pharmacol. 2024 Sep 13. doi: 10.1007/s00228-024-03757-8. Epub ahead of print. PMID: 39271490. 6: Murad B, Reis PCA, Deberaldini Marinho A, Marin Comini AC, Pinheiro Xavier D, Mella Soares Pessoa B, Raheem F, Ernst B, Mina LA, Batalini F. QTc prolongation across CDK4/6 inhibitors: a systematic review and meta-analysis of randomized controlled trials. JNCI Cancer Spectr. 2024 Sep 10:pkae078. doi: 10.1093/jncics/pkae078. Epub ahead of print. PMID: 39254653. 7: Jiang YC, Yang JJ, Zhang HT, Zhuo R, De La Roche S, Torres-De La Roche LA, De Wilde RL, Dong J. First‑line endocrine therapy for hormone receptor positive and HER‑2 negative metastatic breast cancer: A Bayesian network meta‑analysis. Oncol Lett. 2024 Aug 28;28(5):513. doi: 10.3892/ol.2024.14646. PMID: 39247493; PMCID: PMC11378012. 8: Natarajan A, Tolaney SM. Is adjuvant ribociclib ready for prime time? Ann Oncol. 2024 Sep 4:S0923-7534(24)03921-8. doi: 10.1016/j.annonc.2024.08.2341. Epub ahead of print. PMID: 39241962. 9: Liu I, Alencastro Veiga Cruzeiro G, Bjerke L, Rogers RF, Grabovska Y, Beck A, Mackay A, Barron T, Hack OA, Quezada MA, Molinari V, Shaw ML, Perez-Somarriba M, Temelso S, Raynaud F, Ruddle R, Panditharatna E, Englinger B, Mire HM, Jiang L, Nascimento A, LaBelle J, Haase R, Rozowsky J, Neyazi S, Baumgartner AC, Castellani S, Hoffman SE, Cameron A, Morrow M, Nguyen QD, Pericoli G, Madlener S, Mayr L, Dorfer C, Geyeregger R, Rota C, Ricken G, Ligon KL, Alexandrescu S, Cartaxo RT, Lau B, Uphadhyaya S, Koschmann C, Braun E, Danan-Gotthold M, Hu L, Siletti K, Sundström E, Hodge R, Lein E, Agnihotri S, Eisenstat DD, Stapleton S, King A, Bleil C, Mastronuzzi A, Cole KA, Waanders AJ, Montero Carcaboso A, Schüller U, Hargrave D, Vinci M, Carceller F, Haberler C, Slavc I, Linnarsson S, Gojo J, Monje M, Jones C, Filbin MG. GABAergic neuronal lineage development determines clinically actionable targets in diffuse hemispheric glioma, H3G34-mutant. Cancer Cell. 2024 Aug 27:S1535-6108(24)00305-2. doi: 10.1016/j.ccell.2024.08.006. Epub ahead of print. PMID: 39232581. 10: O'Keefe K, Desai NV, Tan AR. Practical Guidance on Abemaciclib in Combination with Adjuvant Endocrine Therapy for Treating Hormone Receptor- Positive, Human Epidermal Growth Factor Receptor 2-Negative High-Risk Early Breast Cancer. Breast Cancer (Dove Med Press). 2024 Aug 29;16:517-527. doi: 10.2147/BCTT.S271441. PMID: 39224861; PMCID: PMC11368096. 11: Kim JH. Profiling the Cardiovascular Toxicities of CDK4/6 Inhibitors: A Real-World Pharmacovigilance Study. Cancers (Basel). 2024 Aug 17;16(16):2869. doi: 10.3390/cancers16162869. PMID: 39199640; PMCID: PMC11352810. 12: Baghermanesh SS, Barati M, Hosseini A. The effect of ribociclib on the expression levels of miR-141 and CDK4/6-USP51 signaling pathway genes in MCF-7 and MDA-MB-231 cells. PLoS One. 2024 Aug 28;19(8):e0309289. doi: 10.1371/journal.pone.0309289. PMID: 39196911; PMCID: PMC11355560. 13: Swain S, Schlam I, Smith DM, Peer C, Sissung T, Schmidt K, Tan M, Chitalia A, Bishopric N, Steinberg S, Choo-Wosoba H, Napoli G, Gallagher C, Ashai N, Whitaker K, Mainor C, Tiwari S, Swanson N, Malloy S, Isaacs C, Figg W. Pharmacokinetics and Pharmacogenomics of Ribociclib in Black Patients with Metastatic Breast Cancer: The LEANORA study. Res Sq [Preprint]. 2024 Aug 13:rs.3.rs-4656461. doi: 10.21203/rs.3.rs-4656461/v1. PMID: 39184092; PMCID: PMC11343304. 14: Ramírez Stieben LA, Vargas MC, Polillo DC, Lufft K, Saldías PR, Bedini I. Metastasis of breast cancer to the thyroid gland. Medicina (B Aires). 2024;84(4):741-745. English. PMID: 39172574. 15: Weiss AM, Lopez MA 2nd, Rosenberger MG, Kim JY, Shen J, Chen Q, Ung T, Ibeh UM, Knight HR, Rutledge NS, Studnitzer B, Rowan SJ, Esser-Kahn AP. Identification of CDK4/6 Inhibitors as Small Molecule NLRP3 Inflammasome Activators that Facilitate IL-1β Secretion and T Cell Adjuvanticity. J Med Chem. 2024 Sep 12;67(17):14974-14985. doi: 10.1021/acs.jmedchem.4c00516. Epub 2024 Aug 20. PMID: 39162654. 16: Guan X, Li M, Ji X, Wang Y, Tian L. Confirming the efficacy and safety of CDK4/6 inhibitors in the first-line treatment of HR+ advanced breast cancer: a systematic review and meta-analysis. Front Pharmacol. 2024 Aug 5;15:1369420. doi: 10.3389/fphar.2024.1369420. PMID: 39161906; PMCID: PMC11330780. 17: Yang WC, Wei MF, Lee YH, Huang CS, Kuo SH. Radiosensitizing effects of CDK4/6 inhibitors in hormone receptor-positive and HER2-negative breast cancer mediated downregulation of DNA repair mechanism and NF-κB-signaling pathway. Transl Oncol. 2024 Nov;49:102092. doi: 10.1016/j.tranon.2024.102092. Epub 2024 Aug 16. PMID: 39153367; PMCID: PMC11381799. 18: Dajsakdipon T, Susiriwatananont T, Wongkraisri C, Ithimakin S, Parinyanitikul N, Supavavej A, Dechaphunkul A, Sunpaweravong P, Neesanun S, Akewanlop C, Dejthevaporn T; TSCO Breast Oncology Group. Comparative effectiveness analysis of survival with first-line palbociclib or ribociclib plus AI in HR + /HER2- advanced breast cancer (CEPRA study): preliminary analysis of real-world data from Thailand. BMC Cancer. 2024 Aug 16;24(1):1018. doi: 10.1186/s12885-024-12765-x. PMID: 39152401; PMCID: PMC11328387. 19: Lim SH, Lee SY, Hong JY, Lee J, Kim ST. CDK4/6 inhibition to resensitize BRAF/EGFR inhibitor in patient-derived BRAF/PTEN-mutant colon cancer cells. Transl Cancer Res. 2024 Jul 31;13(7):3695-3703. doi: 10.21037/tcr-24-20. Epub 2024 Jul 12. PMID: 39145064; PMCID: PMC11319972. 20: Wen Y, Sun X, Zeng L, Liang S, Li D, Chen X, Zeng F, Zhang C, Wang Q, Zhong Q, Deng L, Guo L. CDK4/6 Inhibitors Impede Chemoresistance and Inhibit Tumor Growth of Small Cell Lung Cancer. Adv Sci (Weinh). 2024 Aug 13:e2400666. doi: 10.1002/advs.202400666. Epub ahead of print. PMID: 39136283.