Identification
- Summary
Alectinib is a kinase inhibitor used to treat anaplastic lymphoma kinase positive metastatic non small cell lung cancer.
- Brand Names
- Alecensa, Alecensaro
- Generic Name
- Alectinib
- DrugBank Accession Number
- DB11363
- Background
Alectinib is a second generation oral drug that selectively inhibits the activity of anaplastic lymphoma kinase (ALK) tyrosine kinase. It is specifically used in the treatment of non-small cell lung cancer (NSCLC) expressing the ALK-EML4 (echinoderm microtubule-associated protein-like 4) fusion protein that causes proliferation of NSCLC cells. Inhibition of ALK prevents phosphorylation and subsequent downstream activation of STAT3 and AKT resulting in reduced tumour cell viability.
Approved under accelerated approval in 2015, alectinib is indicated for use in patients who have progressed on or were not tolerant of crizotinib, which is associated with the development of resistance.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Alectinib (DB11363)
- Weight
- Average: 482.6166
Monoisotopic: 482.268176352 - Chemical Formula
- C30H34N4O2
- Synonyms
- 9-ethyl-6,6-dimethyl-8-[4-(morpholin-4-yl)piperidin-1-yl]-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile
- Alectinib
- External IDs
- AF 802
- AF-802
- AF802
- CH 5424802
- CH-5424802
- CH5424802
- RO-5424802
- RO5424802
Pharmacology
- Indication
Alectinib is a kinase inhibitor indicated for the treatment of patients with anaplastic lymphoma kinase (ALK)-positive, metastatic non-small cell lung cancer (NSCLC) who have progressed on or are intolerant to crizotinib. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Refractory, metastatic non-small cell lung cancer •••••••••••• - Contraindications & Blackbox Warnings
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Not Available
- Mechanism of action
Alectinib is a second generation oral drug that selectively inhibits the activity of anaplastic lymphoma kinase (ALK) tyrosine kinase. It is specifically used in the treatment of non-small cell lung cancer (NSCLC) expressing the ALK-EML4 (echinoderm microtubule-associated protein-like 4) fusion protein that causes proliferation of NSCLC cells. Inhibition of ALK prevents phosphorylation and subsequent downstream activation of STAT3 and AKT resulting in reduced tumour cell viability. Both alectinib and its major active metabolite M4 demonstrate similar in vivo and in vitro activity against multiple mutant forms of ALK.
Target Actions Organism AALK tyrosine kinase receptor inhibitorHumans - Absorption
Alectinib reached maximal concentrations at 4 hours following administration of 600 mg twice daily under fed conditions in patients with ALK-positive NSCLC. The absolute bioavailability was 37% in the fed state. A high-fat, high-calorie meal increased the combined exposure of alectinib and its major metabolite M4 by 3.1-fold following oral administration of a single 600 mg dose.
- Volume of distribution
4016 L
- Protein binding
Alectinib and its major metabolite M4 are >99% bound to human plasma proteins.
- Metabolism
Alectinib is metabolized by CYP3A4 to its major active metabolite M4. M4 is then further metabolized by CYP3A4. Both alectinib and M4 demonstrate similar in vivo and in vitro activity. In vitro studies suggest that alectinib is not a substrate for P-gp while M4 is.
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- Route of elimination
When radioactively labeled, 98% of radioactivity was found in feces with 84% of that amount excreted as unchanged alectinib and 6% as M4. Less than 0.5% was found to be recovered in urine.
- Half-life
The mean elimination half life is 33 hr for alectinib and 31 hr for M4.
- Clearance
The apparent clearance is 81.9L/hr for alectinib and 217 L/hr for M4.
- Adverse Effects
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The most common adverse reactions (>5%) associated with alectinib use were fatigue, constipation, edema, and myalgia. Less common effects associated with use were hepatotoxicity, interstitial lung disease (ILD)/pneumonitis, bradycardia, severe myalgia and creatine phosphokinase (CPK) elevation, and embryo-fetal toxicity. Females of reproductive potential are advised to use effective contraception during treatment with alectinib and for 1 week following the final dose.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- 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.
Drug Interaction Integrate drug-drug
interactions in your softwareAbatacept The metabolism of Alectinib can be increased when combined with Abatacept. Abemaciclib Alectinib may decrease the excretion rate of Abemaciclib which could result in a higher serum level. Acalabrutinib The metabolism of Alectinib can be decreased when combined with Acalabrutinib. Acetaminophen The metabolism of Alectinib can be increased when combined with Acetaminophen. Acetazolamide The serum concentration of Alectinib can be increased when it is combined with Acetazolamide. - Food Interactions
- Exercise caution with grapefruit products. Grapefruit inhibits CYP3A4 metabolism, which may increase the serum concentration of alectinib.
- Exercise caution with St. John's Wort. This herb induces CYP3A metabolism, which may reduce serum levels of alectinib.
- Take with food.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Ingredients
Ingredient UNII CAS InChI Key Alectinib hydrochloride P9YY73LO6J 1256589-74-8 GYABBVHSRIHYJR-UHFFFAOYSA-N - International/Other Brands
- Alecensa
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Alecensa Capsule 150 mg Oral Roche Registration Gmb H 2020-12-16 Not applicable EU 
Alecensa Capsule 150 mg/1 Oral Genentech, Inc. 2015-12-11 Not applicable US 
Alecensa Capsule 150 mg Oral Roche Registration Gmb H 2020-12-16 Not applicable EU Alecensaro Capsule 150 mg Oral Hoffmann La Roche 2016-10-14 Not applicable Canada 
Categories
- ATC Codes
- L01ED03 — Alectinib
- Drug Categories
- Anaplastic lymphoma kinase (ALK) inhibitors
- Antineoplastic Agents
- Antineoplastic and Immunomodulating Agents
- BCRP/ABCG2 Inhibitors
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 Substrates
- Enzyme Inhibitors
- Heterocyclic Compounds, Fused-Ring
- Indoles
- Kinase Inhibitor
- Narrow Therapeutic Index Drugs
- P-glycoprotein inhibitors
- P-glycoprotein substrates
- Protein Kinase Inhibitors
- Tyrosine Kinase Inhibitors
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as carbazoles. These are compounds containing a three ring system containing a pyrrole ring fused on either side to a benzene ring.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Indoles and derivatives
- Sub Class
- Carbazoles
- Direct Parent
- Carbazoles
- Alternative Parents
- Naphthalenes / Indoles / Aryl ketones / Dialkylarylamines / Aminopiperidines / Morpholines / Vinylogous amides / Heteroaromatic compounds / Pyrroles / Trialkylamines show 7 more
- Substituents
- 4-aminopiperidine / Amine / Aromatic heteropolycyclic compound / Aryl ketone / Azacycle / Benzenoid / Carbazole / Carbonitrile / Dialkyl ether / Dialkylarylamine show 22 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- LIJ4CT1Z3Y
- CAS number
- 1256580-46-7
- InChI Key
- KDGFLJKFZUIJMX-UHFFFAOYSA-N
- InChI
- InChI=1S/C30H34N4O2/c1-4-20-16-23-24(17-26(20)34-9-7-21(8-10-34)33-11-13-36-14-12-33)30(2,3)29-27(28(23)35)22-6-5-19(18-31)15-25(22)32-29/h5-6,15-17,21,32H,4,7-14H2,1-3H3
- IUPAC Name
- 9-ethyl-6,6-dimethyl-8-[4-(morpholin-4-yl)piperidin-1-yl]-11-oxo-5H,6H,11H-benzo[b]carbazole-3-carbonitrile
- SMILES
- CCC1=CC2=C(C=C1N1CCC(CC1)N1CCOCC1)C(C)(C)C1=C(C3=CC=C(C=C3N1)C#N)C2=O
References
- General References
- McKeage K: Alectinib: a review of its use in advanced ALK-rearranged non-small cell lung cancer. Drugs. 2015 Jan;75(1):75-82. doi: 10.1007/s40265-014-0329-y. [Article]
- Sakamoto H, Tsukaguchi T, Hiroshima S, Kodama T, Kobayashi T, Fukami TA, Oikawa N, Tsukuda T, Ishii N, Aoki Y: CH5424802, a selective ALK inhibitor capable of blocking the resistant gatekeeper mutant. Cancer Cell. 2011 May 17;19(5):679-90. doi: 10.1016/j.ccr.2011.04.004. [Article]
- Kodama T, Tsukaguchi T, Yoshida M, Kondoh O, Sakamoto H: Selective ALK inhibitor alectinib with potent antitumor activity in models of crizotinib resistance. Cancer Lett. 2014 Sep 1;351(2):215-21. doi: 10.1016/j.canlet.2014.05.020. Epub 2014 Jun 2. [Article]
- Sullivan I, Planchard D: ALK inhibitors in non-small cell lung cancer: the latest evidence and developments. Ther Adv Med Oncol. 2016 Jan;8(1):32-47. doi: 10.1177/1758834015617355. [Article]
- External Links
- KEGG Drug
- D10542
- PubChem Compound
- 49806720
- PubChem Substance
- 310265230
- ChemSpider
- 26326738
- BindingDB
- 50362781
- 1727455
- ChEBI
- 90936
- ChEMBL
- CHEMBL1738797
- ZINC
- ZINC000066166864
- PharmGKB
- PA166160050
- PDBe Ligand
- EMH
- RxList
- RxList Drug Page
- Wikipedia
- Alectinib
- PDB Entries
- 3aox / 5xv7
- FDA label
- Download (581 KB)
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 4 Recruiting Treatment ALK Gene Translocation / Drug Monitoring / Lung Cancer / Non-Small Cell Lung Carcinoma / Positive for Anaplastic Lymphoma Kinase 1 3 Active Not Recruiting Treatment ALK+ Advanced NSCLC 1 3 Active Not Recruiting Treatment Anaplastic Lymphoma Kinase-positive Non-small Cell Lung Cancer 1 3 Active Not Recruiting Treatment Non-Small Cell Lung Cancer (NSCLC) 1 3 Active Not Recruiting Treatment Non-Small Cell Lung Carcinoma 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Capsule Oral Capsule Oral 150 mg/1 Capsule Oral 161.33 MG Capsule, coated Oral 150 mg Capsule Oral 150 mg - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US9126931 No 2015-09-08 2031-05-29 US US9440922 No 2016-09-13 2030-06-09 US US9365514 No 2016-06-14 2032-03-04 US US10350214 No 2019-07-16 2035-04-24 US US11433076 No 2015-04-24 2035-04-24 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source pKa 7.05 FDA Label - Predicted Properties
Property Value Source Water Solubility 0.0105 mg/mL ALOGPS logP 5.59 ALOGPS logP 4.89 Chemaxon logS -4.7 ALOGPS pKa (Strongest Acidic) 12.18 Chemaxon pKa (Strongest Basic) 7.59 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 5 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 72.36 Å2 Chemaxon Rotatable Bond Count 3 Chemaxon Refractivity 155.11 m3·mol-1 Chemaxon Polarizability 56.56 Å3 Chemaxon Number of Rings 6 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-001i-0001900000-85ef76c1ea416bc3f259 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-001i-0000900000-8d745b712d02d9e34a3d Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-001i-0001900000-bb9b29a755380e7e0af3 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-001i-0000900000-acaa3ca05a01049e1d14 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-0pvi-3902400000-3237cf047324a301beca Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-0uel-1000900000-b5386752d62e248f48ba Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 210.11423 predictedDeepCCS 1.0 (2019) [M+H]+ 212.47224 predictedDeepCCS 1.0 (2019) [M+Na]+ 218.86176 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Transmembrane receptor protein tyrosine kinase activity
- Specific Function
- Neuronal orphan receptor tyrosine kinase that is essentially and transiently expressed in specific regions of the central and peripheral nervous systems and plays an important role in the genesis a...
- Gene Name
- ALK
- Uniprot ID
- Q9UM73
- Uniprot Name
- ALK tyrosine kinase receptor
- Molecular Weight
- 176440.535 Da
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- 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
- 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 at January 19, 2016 19:11 / Updated at September 06, 2023 02:10