Identification

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
  • LY2835219
External IDs
LY-2835219 / LY2835219
Product Ingredients
IngredientUNIICASInChI Key
Abemaciclib MesylateKKT462Q8071231930-82-7NCJPFQPEVDHJAZ-UHFFFAOYSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
VerzenioTablet50 mg/1OralEli Lilly and Company2017-09-28Not applicableUs
VerzenioTablet150 mg/1OralEli Lilly and Company2017-09-28Not applicableUs
VerzenioTablet100 mg/1OralEli Lilly and Company2017-09-28Not applicableUs
VerzenioTablet200 mg/1OralEli Lilly and Company2017-09-28Not applicableUs
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
Human
ACyclin-dependent kinase 6
inhibitor
Human
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
DrugInteraction
(R)-warfarinThe metabolism of Abemaciclib can be decreased when combined with (R)-warfarin.
(S)-WarfarinThe metabolism of (S)-Warfarin can be decreased when combined with Abemaciclib.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Abemaciclib.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Abemaciclib.
5-androstenedioneThe metabolism of Abemaciclib can be decreased when combined with 5-androstenedione.
6-Deoxyerythronolide BThe metabolism of Abemaciclib can be decreased when combined with 6-Deoxyerythronolide B.
6-O-benzylguanineThe metabolism of Abemaciclib can be decreased when combined with 6-O-benzylguanine.
9-aminocamptothecinThe metabolism of 9-aminocamptothecin can be decreased when combined with Abemaciclib.
AbirateroneThe metabolism of Abemaciclib can be decreased when combined with Abiraterone.
AcalabrutinibThe metabolism of Abemaciclib can be decreased when combined with Acalabrutinib.
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
PDB Entries
5l2s
FDA label
Download (325 KB)
MSDS
Download (23.8 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1Active Not RecruitingBasic ScienceNeoplasms Metastasis1
1Active Not RecruitingTreatmentCancer, Advanced1
1Active Not RecruitingTreatmentCancer, Advanced / Colorectal Cancers / Mantle Cell Lymphoma (MCL)1
1Active Not RecruitingTreatmentCancer, Advanced / Metastatic Cancers1
1Active Not RecruitingTreatmentCancer, Breast / Cholangiocarcinomas / Malignant Neoplasm of Colon / Soft Tissue Sarcoma (STS) / Tumors, Solid1
1Active Not RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC) / Neoplasms Metastasis1
1Active Not RecruitingTreatmentMalignant Lymphomas / Neoplasms Metastasis1
1Active Not RecruitingTreatmentNon-Small Cell Lung Carcinoma (NSCLC)1
1CompletedBasic ScienceHealthy Volunteers8
1CompletedBasic ScienceHealthy Volunteers / Hepatic Insufficiency1
1CompletedBasic ScienceNeoplasms / Neoplasms Metastasis1
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
1RecruitingTreatmentCancer, Advanced / Lung Cancer Non-Small Cell Cancer (NSCLC) / Mesothelioma, Malignant / Metastatic Breast Cancer (MBC) / Metastatic Cancers / Non-Hodgkin's Lymphoma (NHL)1
1RecruitingTreatmentCancer, Breast / Lung Cancer Non-Small Cell Cancer (NSCLC)1
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
1, 2Not Yet RecruitingTreatmentHead and Neck Squamous Cell Carcinoma (HNSCC)1
2Active Not RecruitingTreatmentAdvanced Non-Small Cell Lung Cancer1
2Active Not RecruitingTreatmentCancer, Breast / 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 Cancer (MBC)2
2Active Not RecruitingTreatmentPancreatic Ductal Adenocarcinoma1
2CompletedTreatmentCancer, Breast / Early-Stage Breast Carcinoma / Hormone Receptor Positive Tumor1
2Not Yet RecruitingTreatmentAdenocarcinoma Of Esophagus / Cholangiocarcinomas / Endometrial Cancers / Esophagus SCC / Urothelial/Bladder Cancer, Nos1
2Not Yet RecruitingTreatmentEndometrial Cancers1
2Not Yet RecruitingTreatmentMesothelioma, Malignant1
2RecruitingPreventionHNSCC / Neoplasms, Head and Neck2
2RecruitingTreatmentAdenocarcinoma of Endometrium1
2RecruitingTreatmentCancer, Advanced / Head and Neck Carcinoma / Metastatic Cancers1
2RecruitingTreatmentCancer, Breast2
2RecruitingTreatmentGlioblastomas1
2RecruitingTreatmentLiposarcomas, Dedifferentiated / Sarcomas1
2RecruitingTreatmentMalignancies1
2RecruitingTreatmentMetastatic Breast Cancer (MBC)1
2RecruitingTreatmentNeoplasms, Brain1
2RecruitingTreatmentProstate Cancer1
3Active Not RecruitingTreatmentCancer, Breast2
3Active Not RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
3Active Not RecruitingTreatmentNeoplasms, Breast1
3RecruitingTreatmentCancer, Breast1
Not AvailableApproved for MarketingNot AvailableMetastatic Breast Cancer (MBC)1

Pharmacoeconomics

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

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
Human
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
Human
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
Human
Pharmacological action
Unknown
Actions
Substrate
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

Carriers

Kind
Protein
Organism
Human
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
Human
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
Human
Pharmacological action
Unknown
Actions
Substrate
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
Human
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
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Phospholipid binding
Specific Function
Not Available
Gene Name
OTC
Uniprot ID
P00480
Uniprot Name
Ornithine carbamoyltransferase, mitochondrial
Molecular Weight
39934.775 Da
Kind
Protein
Organism
Human
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
Kind
Protein
Organism
Human
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

Drug created on October 20, 2016 15:09 / Updated on November 02, 2018 09:02