Identification

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Name
Abemaciclib
Accession Number
DB12001
Type
Small Molecule
Groups
Approved, Investigational
Description

Abemaciclib is an antitumor agent and dual inhibitor of cyclin-dependent kinases 4 (CDK4) and 6 (CDK6) that are involved in the cell cycle and promotion of cancer cell growth in case of unregulated activity. On September 28, 2017, FDA granted approval of abemaciclib treatment under the market name Verzenio for the treatment of HR-positive and HER2-negative advanced or metastatic breast cancer that has progressed after unsuccessful endocrine therapy. It is either given alone in patients who has undergone endocrine therapy and chemotherapy after the metastasis of cancer, or in combination with Fulvestrant. Following oral treatment in patients with HR-positive, HER2-negative breast cancer, abemaciclib demonstrated increased progression-free survival rates and objective response rates. Abemaciclib has been used in trials studying the treatment of melanoma, lymphoma, neoplasm, solid tumor, and glioblastoma.

Structure
Thumb
Synonyms
  • Abemaciclib
External IDs
LY-2835219 / LY2835219
Product Ingredients
IngredientUNIICASInChI Key
Abemaciclib mesylateKKT462Q8071231930-82-7NCJPFQPEVDHJAZ-UHFFFAOYSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
VerzenioTablet200 mgOralEli Lilly & Co. Ltd.2019-07-03Not applicableCanada
VerzenioTablet100 mg/1OralEli Lilly and Company2017-09-28Not applicableUs
VerzenioTablet150 mgOralEli Lilly & Co. Ltd.2019-07-03Not applicableCanada
VerzenioTablet100 mgOralEli Lilly & Co. Ltd.2019-07-03Not applicableCanada
VerzenioTablet50 mg/1OralEli Lilly and Company2017-09-28Not applicableUs
VerzenioTablet50 mgOralEli Lilly & Co. Ltd.2019-07-03Not applicableCanada
VerzenioTablet200 mg/1OralEli Lilly and Company2017-09-28Not applicableUs
VerzenioTablet150 mg/1OralEli Lilly and Company2017-09-28Not applicableUs
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Categories
UNII
60UAB198HK
CAS number
1231929-97-7
Weight
Average: 506.606
Monoisotopic: 506.271799388
Chemical Formula
C27H32F2N8
InChI Key
UZWDCWONPYILKI-UHFFFAOYSA-N
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)
IUPAC Name
N-{5-[(4-ethylpiperazin-1-yl)methyl]pyridin-2-yl}-5-fluoro-4-[4-fluoro-2-methyl-1-(propan-2-yl)-1H-1,3-benzodiazol-6-yl]pyrimidin-2-amine
SMILES
CCN1CCN(CC2=CC=C(NC3=NC=C(F)C(=N3)C3=CC(F)=C4N=C(C)N(C(C)C)C4=C3)N=C2)CC1

Pharmacology

Indication
  • Indicated in combination with fulvestrant for the treatment of women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer with disease progression following endocrine therapy.

  • Inidicated as monotherapy for the treatment of adult patients with HR-positive, HER2-negative advanced or metastatic breast cancer with disease progression following endocrine therapy and prior chemotherapy in the metastatic setting.

Associated Conditions
Pharmacodynamics

In combination with fulvestrant, the progression-free survival for patients with HR-positive, HER2-negative breast cancer was 16.4 months compared to 9.3 months for patients taking a placebo with fulvestrant. As a monotherapy, 19.7% of patients taking abemaciclib achieved complete or partial shrinkage of their tumors for a median 8.6 months after treatment 5. Abemaciclib induces cell cycle arrest and exerts an antitumor activity in human tumor xenograft models 1.

In patient investigations and a healthy volunteer study, abemaciclib is not shown to induce any clinically significant changes in the QTc interval Label.

Mechanism of action

Regulation of cell cycle is crucial in maintaining proper cell growth; dysregulated cell cycle signalling pathway is a key component in inducing hyperproliferation of cells and tumor formation in various cancers. G1 to S phase cell cycle progression, or transition through the G1 restriction point (R), is promoted by the retinoblastoma tumor suppressor protein (Rb)-mediated pathway. Activation of Rb-mediated pathway requires the interaction of Cyclin-dependent kinases (CDK) 4 and 6 with D-type cyclins, which drives the formation of active CDK4/CDK6 and subsequent phosphorylation of Rb 1,2.

Rb is a tumor suppressant protein that inhibits proliferation through binding to and suppressing the activity of the E2F family of transcription factors 1. However, phosphorylation of Rb relieves suppression of E2F to allow expression of genes required for passage through the restriction point 1. This leads to increased expression of downstream signalling molecules and activity of protein kinases that promote the cell cycle progression and initiation of DNA replication. Phosphorylation of Rb and other proteins by CDK4/6 additionally leads to transcription of genes involved in cell cycle-independent activities including signal transduction, DNA repair transcriptional control, and mRNA processing 1.

Abemaciclib selectively inhibits CDK4 and CDK6 with low nanomolar potency, inhibits Rb phosphorylation resulting in a G1 arrest and inhibition of proliferation, and its activity is specific for Rb-proficient cells 1. Unlike other CDK inhibitors such as Palbociclib and Ribociclib, abemaciclib exhibits greater selectivity for CDK4 compared to CDK6 2.

TargetActionsOrganism
ACyclin-dependent kinase 4
inhibitor
Humans
ACyclin-dependent kinase 6
inhibitor
Humans
Additional Data Available
Adverse Effects

Comprehensive structured data on known drug adverse effects with statistical prevalence. MedDRA and ICD10 ids are provided for adverse effect conditions and symptoms.

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Additional Data Available
Contraindications

Structured data covering drug contraindications. Each contraindication describes a scenario in which the drug is not to be used. Includes restrictions on co-administration, contraindicated populations, and more.

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Additional Data Available
Blackbox Warnings

Structured data representing warnings from the black box section of drug labels. These warnings cover important and dangerous risks, contraindications, or adverse effects.

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Absorption

The plasma concentration of the drug increases in a dose-proportional manner. Following a single oral dose administration of 200 mg abemaciclib, the mean peak plasma concentration (Cmax) of 158 ng/mL is reached after 6 hours. The median time to reach maximum plasma concentration (Tmax) ranges from 4-6 hours following an oral administration of abemaciclib over a range of 50–275 mg 2, but may range up to 24 hours Label. The absolute bioavailability of the drug is reported to be 45% Label.

Volume of distribution

The geometric mean systemic volume of distribution is approximately 690.3 L (49% CV) Label.

Protein binding

According to in vitro models using animal brain tissues, the protein binding of abemaciclib is approximately 95-98% 4. While abemaciclib demonstrated in vitro binding to serum albumin, alpha-1-acid glycoprotein and other human plasma proteins in a concentration-depedent manner, its major metabolites are also shown to bind to plasms proteins as well. The approximate bound fractions of M2, M18 and M20 are 93.4%, 96.8% and 97.8%, respectively Label.

Metabolism

Abemaciclib mainly undergoes hepatic metabolism mediated by CYP3A4. The major metabolite formed is N-desethylabemaciclib (M2), while other metabolites hydroxyabemaciclib (M20), hydroxy-N-desethylabemaciclib (M18), and an oxidative metabolite (M1) are also formed. M2, M18, and M20 are equipotent to abemaciclib and their AUCs accounted for 25%, 13%, and 26% of the total circulating analytes in plasma, respectively Label.

Route of elimination

Following a single oral dose of 150mg radiolabeled abemaciclib, approximately 81% of the total dose was recovered in feces while 3% of the dose was detected in urine. The majority of the drug is exceted as metabolites Label.

Half life

The mean plasma elimination half-life for abemaciclib in patients was 18.3 hours (72% CV) Label.

Clearance

The geometric mean hepatic clearance (CL) of abemaciclib in patients was 26.0 L/h (51% CV) Label.

Toxicity

According to the bacterial reverse mutation (Ames) assay, abemaciclib and its active metbolites M2 and M20 did not display mutagenic properties. Abemaciclib was not clastogenic in vitro rat bone marrow micronucleus assay. Repeat-dose toxicity studies were performed to assess the effects of abemaciclib in testis, epididymis, prostate, and seminal vesicle at doses ≥10 mg/kg/day in rats and ≥0.3 mg/kg/day in dogs which exceed the recommeded therapeutic doses in humans. The findings included decreased organ weights, intratubular cellular debris, hypospermia, tubular distillation, atrophy and degeneration or necrosis Label.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AcebutololThe serum concentration of Acebutolol can be increased when it is combined with Abemaciclib.
AcetaminophenThe serum concentration of Abemaciclib can be increased when it is combined with Acetaminophen.
AcetyldigoxinAbemaciclib may decrease the excretion rate of Acetyldigoxin which could result in a higher serum level.
Acetylsalicylic acidThe serum concentration of Acetylsalicylic acid can be increased when it is combined with Abemaciclib.
AcyclovirThe excretion of Abemaciclib can be decreased when combined with Acyclovir.
AfatinibThe serum concentration of Afatinib can be increased when it is combined with Abemaciclib.
AlbendazoleThe serum concentration of Abemaciclib can be increased when it is combined with Albendazole.
AldosteroneThe serum concentration of Aldosterone can be increased when it is combined with Abemaciclib.
AlectinibThe serum concentration of Abemaciclib can be increased when it is combined with Alectinib.
AlfentanilThe serum concentration of Alfentanil can be increased when it is combined with Abemaciclib.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

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  • Action
    Action

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Food Interactions
Not Available

References

General References
  1. Gelbert LM, Cai S, Lin X, Sanchez-Martinez C, Del Prado M, Lallena MJ, Torres R, Ajamie RT, Wishart GN, Flack RS, Neubauer BL, Young J, Chan EM, Iversen P, Cronier D, Kreklau E, de Dios A: 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. 2014 Oct;32(5):825-37. doi: 10.1007/s10637-014-0120-7. Epub 2014 Jun 13. [PubMed:24919854]
  2. Patnaik A, Rosen LS, Tolaney SM, Tolcher AW, Goldman JW, Gandhi L, Papadopoulos KP, Beeram M, Rasco DW, Hilton JF, Nasir A, Beckmann RP, Schade AE, Fulford AD, Nguyen TS, Martinez R, Kulanthaivel P, Li LQ, Frenzel M, Cronier DM, Chan EM, Flaherty KT, Wen PY, Shapiro GI: Efficacy and Safety of Abemaciclib, an Inhibitor of CDK4 and CDK6, for Patients with Breast Cancer, Non-Small Cell Lung Cancer, and Other Solid Tumors. Cancer Discov. 2016 Jul;6(7):740-53. doi: 10.1158/2159-8290.CD-16-0095. Epub 2016 May 23. [PubMed:27217383]
  3. Tate SC, Sykes AK, Kulanthaivel P, Chan EM, Turner PK, Cronier DM: A Population Pharmacokinetic and Pharmacodynamic Analysis of Abemaciclib in a Phase I Clinical Trial in Cancer Patients. Clin Pharmacokinet. 2017 May 24. doi: 10.1007/s40262-017-0559-8. [PubMed:28540640]
  4. Raub TJ, Wishart GN, Kulanthaivel P, Staton BA, Ajamie RT, Sawada GA, Gelbert LM, Shannon HE, Sanchez-Martinez C, De Dios A: Brain Exposure of Two Selective Dual CDK4 and CDK6 Inhibitors and the Antitumor Activity of CDK4 and CDK6 Inhibition in Combination with Temozolomide in an Intracranial Glioblastoma Xenograft. Drug Metab Dispos. 2015 Sep;43(9):1360-71. doi: 10.1124/dmd.114.062745. Epub 2015 Jul 6. [PubMed:26149830]
  5. FDA approves new treatment for certain advanced or metastatic breast cancers [Link]
External Links
PubChem Compound
46220502
PubChem Substance
347828320
ChemSpider
29340700
BindingDB
50110183
ChEMBL
CHEMBL3301610
PharmGKB
PA166153471
HET
6ZV
Wikipedia
Abemaciclib
ATC Codes
L01XE50 — Abemaciclib
AHFS Codes
  • 10:00.00 — Antineoplastic Agents
PDB Entries
5l2s
FDA label
Download (325 KB)
MSDS
Download (23.8 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0Not Yet RecruitingTreatmentGBM / Glioblastomas / Neoplasms, Brain / Recurrent Brain Tumors1
0Not Yet RecruitingTreatmentHormone Receptor Positive Malignant Neoplasm of Breast / Locally Advanced Breast Cancer (LABC) / Malignant Neoplasm of Female Breast1
0RecruitingTreatmentBladder Cancers1
0RecruitingTreatmentEndometrial Endometrioid Adenocarcinoma1
1Active Not RecruitingBasic ScienceNeoplasms Metastasis1
1Active Not RecruitingTreatmentBreast Cancer / Cholangiocarcinomas / Malignant Neoplasm of Colon / Soft Tissue Sarcoma (STS) / Tumors, Solid1
1Active Not RecruitingTreatmentBreast Cancer / Lung Cancer Non-Small Cell Cancer (NSCLC)1
1Active Not RecruitingTreatmentCancer, Advanced1
1Active Not RecruitingTreatmentCancer, Advanced / Lung Cancer Non-Small Cell Cancer (NSCLC) / Mesothelioma, Malignant / Metastatic Breast Cancer / Metastatic Cancers / Non-Hodgkin's Lymphoma (NHL)1
1Active Not RecruitingTreatmentCancer, Advanced / Metastatic Cancers1
1Active Not RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
1CompletedBasic ScienceHealthy Volunteers8
1CompletedBasic ScienceHealthy Volunteers / Hepatic Insufficiency1
1CompletedBasic ScienceNeoplasms / Neoplasms Metastasis1
1CompletedTreatmentCancer, Advanced / Colorectal Cancers / Mantle Cell Lymphoma (MCL)1
1CompletedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC) / Neoplasms Metastasis1
1CompletedTreatmentMalignant Lymphomas / Neoplasms Metastasis1
1Not Yet RecruitingTreatmentBreast Cancer1
1Not Yet RecruitingTreatmentCancer, Advanced1
1RecruitingTreatmentBreast Cancer (HR+HER2-) / Cutaneous Melanoma / Malignant Neoplasm of Pancreas / Microsatellite Instability-High (MSI-H) Solid Tumors / Tumors, Solid1
1RecruitingTreatmentCancer, Advanced / Colorectal Cancers / Metastatic Melanoma / Metastatic Non-Small Cell Lung Cancer / Metastatic Pancreatic Ductal Adenocarcinoma1
1RecruitingTreatmentDiffuse Intrinsic Pontine Glioma (DIPG) / Ewing Sarcoma, Recurrent, Refractory / Neuroblastoma, Recurrent, Refractory / Osteosarcoma, Recurrent, Refractory / Recurrent Brain Tumors / Rhabdoid Tumor, Recurrent, Refractory / Rhabdomyosarcoma, Recurrent, Refractory / Solid Tumor, Recurrent1
1RecruitingTreatmentNeoplasms, Breast1
1RecruitingTreatmentNeoplasms / Neoplasms, Breast1
1SuspendedTreatmentRenal Cell Carcinoma Metastatic1
1, 2Not Yet RecruitingTreatmentAnatomic Stage IV Breast Cancer AJCC v8 / ERBB2 Gene Amplification Negative / Estrogen Receptor Positive / HER2/Neu Negative / Hormone Receptor Positive Breast Carcinoma / Metastatic Breast Carcinoma / Progesterone Receptor Positive / Prognostic Stage IV Breast Cancer AJCC v8 / Progressive Disease / Recurrent Breast Carcinoma1
1, 2RecruitingTreatmentHead and Neck Squamous Cell Carcinoma (HNSCC)1
1, 2RecruitingTreatmentNeoplasms, Breast1
1, 2RecruitingTreatmentRelapsed Or Refractory Multiple Myeloma1
2Active Not RecruitingTreatmentAdvanced Non-Small Cell Lung Cancer1
2Active Not RecruitingTreatmentBreast Cancer / Lung Cancer Non-Small Cell Cancer (NSCLC) / Melanoma / Metastatic Brain Tumors1
2Active Not RecruitingTreatmentGlioblastomas1
2Active Not RecruitingTreatmentHER-2 Positive Breast Cancer / Hormone Receptor Positive Tumor1
2Active Not RecruitingTreatmentMantle Cell Lymphoma (MCL)1
2Active Not RecruitingTreatmentMetastatic Breast Cancer2
2CompletedTreatmentBreast Cancer / Early-Stage Breast Carcinoma / Hormone Receptor Positive Tumor1
2CompletedTreatmentMetastatic Breast Cancer1
2CompletedTreatmentPancreatic Ductal Adenocarcinoma1
2Not Yet RecruitingTreatmentAnatomic Stage I Breast Cancer AJCC v8 / Anatomic Stage IA Breast Cancer AJCC v8 / Anatomic Stage IB Breast Cancer AJCC v8 / Anatomic Stage II Breast Cancer AJCC v8 / Anatomic Stage IIA Breast Cancer AJCC v8 / Anatomic Stage IIB Breast Cancer AJCC v8 / Anatomic Stage III Breast Cancer AJCC v8 / Anatomic Stage IIIA Breast Cancer AJCC v8 / Anatomic Stage IIIB Breast Cancer AJCC v8 / Anatomic Stage IIIC Breast Cancer AJCC v8 / Breast Fibrocystic Change / Ductal Breast Carcinoma In Situ / Estrogen Receptor Negative / HER2/Neu Negative / Invasive Breast Carcinoma / Lobular Breast Carcinoma In Situ / Progesterone Receptor Negative / Prognostic Stage I Breast Cancer AJCC v8 / Prognostic Stage IA Breast Cancer AJCC v8 / Prognostic Stage IB Breast Cancer AJCC v8 / Prognostic Stage II Breast Cancer AJCC v8 / Prognostic Stage IIA Breast Cancer AJCC v8 / Prognostic Stage IIB Breast Cancer AJCC v8 / Prognostic Stage III Breast Cancer AJCC v8 / Prognostic Stage IIIA Breast Cancer AJCC v8 / Prognostic Stage IIIB Breast Cancer AJCC v8 / Prognostic Stage IIIC Breast Cancer AJCC v8 / Triple-Negative Breast Carcinoma1
2Not Yet RecruitingTreatmentBiliary Tract Carcinoma1
2Not Yet RecruitingTreatmentGlioblastomas1
2Not Yet RecruitingTreatmentHepatocellular,Carcinoma1
2Not Yet RecruitingTreatmentLung Cancer Small Cell Lung Cancer (SCLC) / Wild Type Rb Extensive Stage SCLC1
2RecruitingPreventionHNSCC / Neoplasms, Head and Neck2
2RecruitingTreatmentAdenocarcinoma Of Esophagus / Cholangiocarcinomas / Endometrial Cancer / Esophagus SCC / Urothelial/Bladder Cancer, Nos1
2RecruitingTreatmentAdenocarcinoma of Endometrium1
2RecruitingTreatmentAdenocarcinomas / Gastrooesophageal Cancer1
2RecruitingTreatmentAdvanced Digestive System Neuroendocrine Neoplasm / Digestive System Neuroendocrine Tumor / Foregut Carcinoid Tumor / Hindgut Carcinoid Tumor / Locally Advanced Unresectable Digestive System Neuroendocrine Neoplasm / Metastatic Digestive System Neuroendocrine Neoplasm / Midgut Carcinoid Tumor / Progressive Neuroendocrine Tumors of pancreatic origin / Refractory Digestive System Neuroendocrine Neoplasm1
2RecruitingTreatmentAdvanced Solid Tumors / Multiple Myeloma (MM) / Non-Hodgkin's Lymphoma (NHL)1
2RecruitingTreatmentBreast Cancer2
2RecruitingTreatmentBreast Cancer / Malignancies1
2RecruitingTreatmentCDK Gene Mutation / Metastatic Malignant Neoplasm in the Brain / Metastatic Malignant Solid Neoplasm / NTRK Family Gene Mutation / PI3K Gene Mutation / ROS1 Gene Mutation1
2RecruitingTreatmentCancer, Advanced / Head and Neck Carcinoma / Metastatic Cancers1
2RecruitingTreatmentChondrosarcomas / Sarcoma, Osteogenic / Soft Tissue Sarcoma (STS)1
2RecruitingTreatmentEndometrial Cancer1
2RecruitingTreatmentGlioblastomas1
2RecruitingTreatmentLiposarcomas, Dedifferentiated / Sarcomas1
2RecruitingTreatmentMalignancies1
2RecruitingTreatmentMalignant Neoplasms of Female Genital Organs1
2RecruitingTreatmentMesothelioma, Malignant1
2RecruitingTreatmentNeoplasms, Brain1
2RecruitingTreatmentOligodendroglioma, Adult1
2RecruitingTreatmentProstate Cancer1
3Active Not RecruitingTreatmentBreast Cancer3
3Active Not RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
3Not Yet RecruitingTreatmentCancer Metastatic1
3RecruitingTreatmentBreast Neoplasm Female1
3RecruitingTreatmentNeoplasms, Breast1
4RecruitingTreatmentMetastatic Breast Cancer1
4WithdrawnTreatmentMetastatic Breast Cancer1
Not AvailableApproved for MarketingNot AvailableMetastatic Breast Cancer1
Not AvailableAvailableNot AvailableMetastatic Breast Cancer1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
TabletOral100 mg
TabletOral100 mg/1
TabletOral150 mg
TabletOral150 mg/1
TabletOral200 mg
TabletOral200 mg/1
TabletOral50 mg/1
TabletOral50 mg
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US7855211No2010-12-212029-12-15Us
Additional Data Available
  • Filed On
    Filed On

    The date on which a patent was filed with the relevant government.

    Learn more

Properties

State
Not Available
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0159 mg/mLALOGPS
logP4.25ALOGPS
logP4.42ChemAxon
logS-4.5ALOGPS
pKa (Strongest Acidic)10.27ChemAxon
pKa (Strongest Basic)7.94ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area75 Å2ChemAxon
Rotatable Bond Count7ChemAxon
Refractivity141.26 m3·mol-1ChemAxon
Polarizability54.75 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as benzimidazoles. These are organic compounds containing a benzene ring fused to an imidazole ring (five member ring containing a nitrogen atom, 4 carbon atoms, and two double bonds).
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Benzimidazoles
Sub Class
Not Available
Direct Parent
Benzimidazoles
Alternative Parents
N-alkylpiperazines / Halopyrimidines / Aralkylamines / Aminopyrimidines and derivatives / Aminopyridines and derivatives / N-substituted imidazoles / Imidolactams / Benzenoids / Aryl fluorides / Heteroaromatic compounds
show 4 more
Substituents
Benzimidazole / Aminopyridine / Aminopyrimidine / Halopyrimidine / Aralkylamine / N-alkylpiperazine / Aryl fluoride / Aryl halide / 1,4-diazinane / N-substituted imidazole
show 18 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Cyclin-dependent protein serine/threonine kinase regulator activity
Specific Function
Ser/Thr-kinase component of cyclin D-CDK4 (DC) complexes that phosphorylate and inhibit members of the retinoblastoma (RB) protein family including RB1 and regulate the cell-cycle during G(1)/S tra...
Gene Name
CDK4
Uniprot ID
P11802
Uniprot Name
Cyclin-dependent kinase 4
Molecular Weight
33729.55 Da
References
  1. Gelbert LM, Cai S, Lin X, Sanchez-Martinez C, Del Prado M, Lallena MJ, Torres R, Ajamie RT, Wishart GN, Flack RS, Neubauer BL, Young J, Chan EM, Iversen P, Cronier D, Kreklau E, de Dios A: 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. 2014 Oct;32(5):825-37. doi: 10.1007/s10637-014-0120-7. Epub 2014 Jun 13. [PubMed:24919854]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Cyclin-dependent protein serine/threonine kinase activity
Specific Function
Serine/threonine-protein kinase involved in the control of the cell cycle and differentiation; promotes G1/S transition. Phosphorylates pRB/RB1 and NPM1. Interacts with D-type G1 cyclins during int...
Gene Name
CDK6
Uniprot ID
Q00534
Uniprot Name
Cyclin-dependent kinase 6
Molecular Weight
36938.025 Da
References
  1. Gelbert LM, Cai S, Lin X, Sanchez-Martinez C, Del Prado M, Lallena MJ, Torres R, Ajamie RT, Wishart GN, Flack RS, Neubauer BL, Young J, Chan EM, Iversen P, Cronier D, Kreklau E, de Dios A: 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. 2014 Oct;32(5):825-37. doi: 10.1007/s10637-014-0120-7. Epub 2014 Jun 13. [PubMed:24919854]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2B6
Uniprot ID
P20813
Uniprot Name
Cytochrome P450 2B6
Molecular Weight
56277.81 Da
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Binder
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
Kind
Protein group
Organism
Humans
Pharmacological action
Unknown
Actions
Binder
General Function
Not Available
Specific Function
Functions as transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in...

Components:

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Monovalent cation:proton antiporter activity
Specific Function
Solute transporter for tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, N-methylnicotinamide (NMN), metformin, creatinine, guanidine, procainamide, topotecan, estrone sulfat...
Gene Name
SLC47A1
Uniprot ID
Q96FL8
Uniprot Name
Multidrug and toxin extrusion protein 1
Molecular Weight
61921.585 Da
References
  1. Patnaik A, Rosen LS, Tolaney SM, Tolcher AW, Goldman JW, Gandhi L, Papadopoulos KP, Beeram M, Rasco DW, Hilton JF, Nasir A, Beckmann RP, Schade AE, Fulford AD, Nguyen TS, Martinez R, Kulanthaivel P, Li LQ, Frenzel M, Cronier DM, Chan EM, Flaherty KT, Wen PY, Shapiro GI: Efficacy and Safety of Abemaciclib, an Inhibitor of CDK4 and CDK6, for Patients with Breast Cancer, Non-Small Cell Lung Cancer, and Other Solid Tumors. Cancer Discov. 2016 Jul;6(7):740-53. doi: 10.1158/2159-8290.CD-16-0095. Epub 2016 May 23. [PubMed:27217383]
  2. Spring LM, Zangardi ML, Moy B, Bardia A: Clinical Management of Potential Toxicities and Drug Interactions Related to Cyclin-Dependent Kinase 4/6 Inhibitors in Breast Cancer: Practical Considerations and Recommendations. Oncologist. 2017 Sep;22(9):1039-1048. doi: 10.1634/theoncologist.2017-0142. Epub 2017 Jul 13. [PubMed:28706010]
  3. Verzenio FDA label [File]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Drug transmembrane transporter activity
Specific Function
Solute transporter for tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, N-methylnicotinamide, metformin, creatinine, guanidine, procainamide, topotecan, estrone sulfate, acy...
Gene Name
SLC47A2
Uniprot ID
Q86VL8
Uniprot Name
Multidrug and toxin extrusion protein 2
Molecular Weight
65083.915 Da
References
  1. Thill M, Schmidt M: Management of adverse events during cyclin-dependent kinase 4/6 (CDK4/6) inhibitor-based treatment in breast cancer. Ther Adv Med Oncol. 2018 Sep 3;10:1758835918793326. doi: 10.1177/1758835918793326. eCollection 2018. [PubMed:30202447]
  2. Abemaciclib FDA label [File]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Quaternary ammonium group transmembrane transporter activity
Specific Function
Mediates tubular uptake of organic compounds from circulation. Mediates the influx of agmatine, dopamine, noradrenaline (norepinephrine), serotonin, choline, famotidine, ranitidine, histamin, creat...
Gene Name
SLC22A2
Uniprot ID
O15244
Uniprot Name
Solute carrier family 22 member 2
Molecular Weight
62579.99 Da
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Xenobiotic-transporting atpase activity
Specific Function
High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both fro...
Gene Name
ABCG2
Uniprot ID
Q9UNQ0
Uniprot Name
ATP-binding cassette sub-family G member 2
Molecular Weight
72313.47 Da
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da

Drug created on October 20, 2016 15:09 / Updated on November 22, 2019 04:24