abemaciclib   Click here for help

GtoPdb Ligand ID: 7382

Synonyms: CS-1230 | HY-16297A | LY 2835219 | LY-2835219  | LY2835219 | Verzenio® | Verzenios®
Approved drug PDB Ligand
abemaciclib is an approved drug (FDA (2017), EMA (2018))
Compound class: Synthetic organic
Comment: Abemaciclib (LY2835219) is a selective ATP-competitive inhibitor of the cyclin-dependent kinases CDK4 and CDK6 [6].
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species

abemaciclib is commercially available from our sponsors

2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 7
Hydrogen bond donors 1
Rotatable bonds 7
Topological polar surface area 75
Molecular weight 506.27
XLogP 4.03
No. Lipinski's rules broken 0

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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Canonical SMILES CCN1CCN(CC1)Cc1ccc(nc1)Nc1ncc(c(n1)c1cc(F)c2c(c1)n(C(C)C)c(n2)C)F
Isomeric SMILES CCN1CCN(CC1)Cc1ccc(nc1)Nc1ncc(c(n1)c1cc(F)c2c(c1)n(C(C)C)c(n2)C)F
InChI InChI=1S/C27H32F2N8/c1-5-35-8-10-36(11-9-35)16-19-6-7-24(30-14-19)33-27-31-15-22(29)25(34-27)20-12-21(28)26-23(13-20)37(17(2)3)18(4)32-26/h6-7,12-15,17H,5,8-11,16H2,1-4H3,(H,30,31,33,34)
InChI Key UZWDCWONPYILKI-UHFFFAOYSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
References
1. Beroukhim R, Mermel CH, Porter D, Wei G, Raychaudhuri S, Donovan J, Barretina J, Boehm JS, Dobson J, Urashima M et al.. (2010)
The landscape of somatic copy-number alteration across human cancers.
Nature, 463 (7283): 899-905. [PMID:20164920]
2. Choi YJ, Li X, Hydbring P, Sanda T, Stefano J, Christie AL, Signoretti S, Look AT, Kung AL, von Boehmer H et al.. (2012)
The requirement for cyclin D function in tumor maintenance.
Cancer Cell, 22 (4): 438-51. [PMID:23079655]
3. Dean JL, McClendon AK, Hickey TE, Butler LM, Tilley WD, Witkiewicz AK, Knudsen ES. (2012)
Therapeutic response to CDK4/6 inhibition in breast cancer defined by ex vivo analyses of human tumors.
Cell Cycle, 11 (14): 2756-61. [PMID:22767154]
4. Gelbert LM, Cai S, Lin X, Sanchez-Martinez C, Del Prado M, Lallena MJ, Torres R, Ajamie RT, Wishart GN, Flack RS et al.. (2014)
Preclinical characterization of the CDK4/6 inhibitor LY2835219: in-vivo cell cycle-dependent/independent anti-tumor activities alone/in combination with gemcitabine.
Invest New Drugs, 32 (5): 825-37. [PMID:24919854]
5. Goel S, Wang Q, Watt AC, Tolaney SM, Dillon DA, Li W, Ramm S, Palmer AC, Yuzugullu H, Varadan V et al.. (2016)
Overcoming Therapeutic Resistance in HER2-Positive Breast Cancers with CDK4/6 Inhibitors.
Cancer Cell, 29 (3): 255-69. [PMID:26977878]
6. Patnaik A, Rosen LS, Tolaney SM, Tolcher AW, Goldman JW, Gandhi L, Papadopoulos KP, Beeram M, Rasco DW, Myrand SP et al.. (2014)
Clinical activity of LY2835219, a novel cell cycle inhibitor selective for CDK4 and CDK6, in patients with metastatic breast cancer.
CT232: AACR Annual Meeting 2014 April 5-9, Meeting abstract.
7. Puyol M, Martín A, Dubus P, Mulero F, Pizcueta P, Khan G, Guerra C, Santamaría D, Barbacid M. (2010)
A synthetic lethal interaction between K-Ras oncogenes and Cdk4 unveils a therapeutic strategy for non-small cell lung carcinoma.
Cancer Cell, 18 (1): 63-73. [PMID:20609353]
8. Sawai CM, Freund J, Oh P, Ndiaye-Lobry D, Bretz JC, Strikoudis A, Genesca L, Trimarchi T, Kelliher MA, Clark M et al.. (2012)
Therapeutic targeting of the cyclin D3:CDK4/6 complex in T cell leukemia.
Cancer Cell, 22 (4): 452-65. [PMID:23079656]
9. Zhang XH, Cheng Y, Shin JY, Kim JO, Oh JE, Kang JH. (2013)
A CDK4/6 inhibitor enhances cytotoxicity of paclitaxel in lung adenocarcinoma cells harboring mutant KRAS as well as wild-type KRAS.
Cancer Biol Ther, 14 (7): 597-605. [PMID:23792647]