Details of the Drug

General Information of Drug (ID: DMP1I6Y)

Drug Name
Alectinib
Synonyms
1256580-46-7; CH5424802; CH 5424802; AF-802; Alecensa; UNII-LIJ4CT1Z3Y; AF 802; LIJ4CT1Z3Y; Alectinib (CH5424802); 9-ethyl-6,6-dimethyl-8-(4-morpholinopiperidin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile; CHEMBL1738797; AF802; 9-Ethyl-6,6-Dimethyl-8-[4-(Morpholin-4-Yl)piperidin-1-Yl]-11-Oxo-6,11-Dihydro-5h-Benzo[b]carbazole-3-Carbonitrile; 9-Ethyl-6,11-dihydro-6,6-dimethyl-8-[4-(4-morpholinyl)-1-piperidinyl]-11-oxo-5H-benzo[b]carbazole-3-carbonitrile; AK170451; C30H34N4O2; Alectinib; 9-ethyl-6,6-dimethyl-
Indication
Disease Entry ICD 11 Status REF
Lung cancer 2C25.0 Approved [1]
Non-small-cell lung cancer 2C25.Y Phase 2 [2]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 1 Molecular Weight (mw) 482.6
Logarithm of the Partition Coefficient (xlogp) 5.2
Rotatable Bond Count (rotbonds) 3
Hydrogen Bond Donor Count (hbonddonor) 1
Hydrogen Bond Acceptor Count (hbondacc) 5
ADMET Property
Clearance
The drug present in the plasma can be removed from the body at the rate of 7.69 mL/min/kg [3]
Half-life
The concentration or amount of drug in body reduced by one-half in 33 hours [3]
Metabolism
The drug is metabolized via the CYP3A4 to its major active metabolite M4 []
Unbound Fraction
The unbound fraction of drug in plasma is 0.003% [3]
Vd
The volume of distribution (Vd) of drug is 4016 L []
Chemical Identifiers
Formula
C30H34N4O2
IUPAC Name
9-ethyl-6,6-dimethyl-8-(4-morpholin-4-ylpiperidin-1-yl)-11-oxo-5H-benzo[b]carbazole-3-carbonitrile
Canonical SMILES
CCC1=CC2=C(C=C1N3CCC(CC3)N4CCOCC4)C(C5=C(C2=O)C6=C(N5)C=C(C=C6)C#N)(C)C
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
InChIKey
KDGFLJKFZUIJMX-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
49806720
ChEBI ID
CHEBI:90936
CAS Number
1256580-46-7
DrugBank ID
DB11363
TTD ID
D0U3SY
INTEDE ID
DR0059
ACDINA ID
D00016
Combinatorial Drugs (CBD) Click to Jump to the Detailed CBD Information of This Drug

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
ALK tyrosine kinase receptor (ALK) TTPMQSO ALK_HUMAN Inhibitor [4]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 3A4 (CYP3A4)
Main DME 		DE4LYSA CP3A4_HUMAN Substrate [5]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
Alanine aminotransferase 1 (GPT) OTOXOA0Q ALAT1_HUMAN Protein Interaction/Cellular Processes [6]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

ICD Disease Classification 02 Neoplasm
Disease Class ICD-11: 2C82 Prostate cancer
The Studied Tissue Lung tissue
The Studied Disease Lung cancer [ICD-11:2C82]
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
ALK tyrosine kinase receptor (ALK) DTT ALK 7.19E-15 0.18 0.61
Cytochrome P450 3A4 (CYP3A4) DME CYP3A4 5.59E-39 -3.76E-01 -1.64E+00
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Alectinib (Comorbidity)
DDI Drug Name DDI Drug ID Severity Mechanism Comorbidity REF
Remdesivir DMBFZ6L Moderate Increased risk of hepatotoxicity by the combination of Alectinib and Remdesivir. 1D6YCoronavirus Disease 2019 [1D6YCoronavirus Disease 2019] [7]
Pexidartinib DMS2J0Z Major Increased risk of hepatotoxicity by the combination of Alectinib and Pexidartinib. Bone/articular cartilage neoplasm [2F7B] [8]
Calaspargase pegol DMQZBXI Moderate Increased risk of hepatotoxicity by the combination of Alectinib and Calaspargase pegol. Malignant haematopoietic neoplasm [2B33] [9]
Siponimod DM2R86O Major Increased risk of bradycardia by the combination of Alectinib and Siponimod. Multiple sclerosis [8A40] [7]
Ozanimod DMT6AM2 Moderate Increased risk of bradycardia by the combination of Alectinib and Ozanimod. Multiple sclerosis [8A40] [10]

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG
DIG Name DIG ID PubChem CID Functional Classification
FD&C blue no. 2 E00446 2723854 Colorant
Glyceryl monooleate E00473 5283468 Bioadhesive material; Emollient; Emulsifying agent; Emulsion stabilizing agent; Gelling agent; Modified-release agent; Surfactant
Potassium chloride E00074 4873 Tonicity agent
Sodium lauryl sulfate E00464 3423265 Emulsifying agent; Modified-release agent; Penetration agent; Solubilizing agent; Surfactant; lubricant
Carboxymethylcellulose sodium E00621 Not Available Adsorbent; Binding agent; Disintegrant; Emulsifying agent; Suspending agent; Viscosity-controlling agent
Eisenoxyd E00585 56841934 Colorant
Ferric hydroxide oxide yellow E00539 23320441 Colorant
Hydroxypropyl cellulose E00632 Not Available Binding agent; Coating agent; Emulsifying agent; Film/Membrane-forming agent; Modified-release agent; Suspending agent; Viscosity-controlling agent
Hypromellose E00634 Not Available Coating agent
Lactose monohydrate E00393 104938 Binding agent; Diluent; Dry powder inhaler carrier; Lyophilization aid
Magnesium stearate E00208 11177 lubricant
Titanium dioxide E00322 26042 Coating agent; Colorant; Opacifying agent
Haematite red E00236 14833 Colorant
Carrageenan E00714 Not Available Emulsion stabilizing agent; Gelling agent; Microencapsulating agent; Modified-release agent; Suspending agent; Viscosity-controlling agent
Pregelatinized starch E00674 Not Available Binding agent; Diluent; Disintegrant
Shellac E00695 Not Available Coating agent; Film/membrane-forming agent; Microencapsulating agent; Modified-release agent
⏷ Show the Full List of 16 Pharmaceutical Excipients of This Drug
Pharmaceutical Formulation
Formulation Name Drug Dosage Dosage Form Route
Alectinib 150 mg capsule 150 mg Oral Capsule Oral
Alectinib Hydrochloride eq 150mg base capsule eq 150mg base Capsule Oral
Jump to Detail Pharmaceutical Formulation Page of This Drug

References

1 Alectinib versus crizotinib in patients with ALK-positive non-small-cell lung cancer (J-ALEX): an open-label, randomised phase 3 trial. Lancet. 2017 Jul 1;390(10089):29-39.
2 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7739).
3 Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
4 CH5424802, a selective ALK inhibitor capable of blocking the resistant gatekeeper mutant. Cancer Cell. 2011 May 17;19(5):679-90.
5 In vitro metabolism of alectinib, a novel potent ALK inhibitor, in human: contribution of CYP3A enzymes. Xenobiotica. 2018 Jun;48(6):546-554.
6 Cytotoxicity of 34 FDA approved small-molecule kinase inhibitors in primary rat and human hepatocytes. Toxicol Lett. 2018 Jul;291:138-148. doi: 10.1016/j.toxlet.2018.04.010. Epub 2018 Apr 12.
7 Cerner Multum, Inc. "Australian Product Information.".
8 Product Information. Turalio (pexidartinib). Daiichi Sankyo, Inc., Parsippany, NJ.
9 Al-Nawakil C, Willems L, Mauprivez C, et.al "Successful treatment of l-asparaginase-induced severe acute hepatotoxicity using mitochondrial cofactors." Leuk Lymphoma 55 (2014): 1670-4. [PMID: 24090500]
10 Product Information. Zeposia (ozanimod). Celgene Corporation, Summit, NJ.