Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DMP1I6Y)

• Drug Name: Alectinib Drug Info
• 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]

• Cross-matching ID:
  PubChem CID: 49806720
  ChEBI ID: CHEBI:90936
  CAS Number: CAS 1256580-46-7
  TTD Drug ID: DMP1I6Y
  INTEDE Drug ID: DR0059
  ACDINA Drug ID: D00016

Molecule-Related Drug Atlas

Drug(s) Targeting ALK tyrosine kinase receptor (ALK)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Crizotinib	DM4F29C	Non-small-cell lung cancer	2C25.Y	Approved	[6]
Lorlatinib	DMICDLV	Non-small-cell lung cancer	2C25.Y	Approved	[7]
Entrectinib	DMMPTLH	Non-small-cell lung cancer	2C25	Approved	[8]
Brigatinib	DM7W94S	Anaplastic large cell lymphoma	2A90.A	Approved	[9]
Repotrectinib	DM9FB2T	Non-small-cell lung cancer	2C25	Approved	[10]
Ceritinib	DMB920Z	Non-small-cell lung cancer	2C25.Y	Approved	[11]
Ensartinib	DMIKDCQ	Non-small-cell lung cancer	2C25.Y	Phase 3	[10]
PF-06463922	DMKM7EW	Non-small-cell lung cancer	2C25.Y	Phase 2	[12]
AP26113	DMYBQEF	Solid tumour/cancer	2A00-2F9Z	Phase 2	[13]
TSR-011	DMFOR9Y	Non-small-cell lung cancer	2C25.Y	Phase 1/2	[14]

Drug(s) Metabolized By Cytochrome P450 3A4 (CYP3A4)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[15]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[16]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[17]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[18]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[19]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[20]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[21]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[22]
Prasterone	DM67VKL	Chronic obstructive pulmonary disease	CA22	Approved	[16]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[23]

Drug(s) Affected By Alanine aminotransferase 1 (GPT)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Halothane	DM80OZ5	Anaesthesia	9A78.6	Approved	[24]
Isoniazid	DM5JVS3	Latent tuberculosis infection		Approved	[25]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[26]
Primidone	DM0WX6I	Epilepsy	8A60-8A68	Approved	[24]
Ciprofloxacin XR	DM2NLS9	Acute gonococcal cervicitis		Approved	[24]
Cocaine	DMSOX7I	Anaesthesia	9A78.6	Approved	[24]
Gefitinib	DM15F0X	Colon adenocarcinoma		Approved	[5]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[27]
Lapatinib	DM3BH1Y	Breast cancer	2C60-2C65	Approved	[5]
Crizotinib	DM4F29C	Non-small-cell lung cancer	2C25.Y	Approved	[5]

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	[3]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4) Main DME	DE4LYSA	CP3A4_HUMAN	Substrate	[4]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Alanine aminotransferase 1 (GPT)	OTOXOA0Q	ALAT1_HUMAN	Protein Interaction/Cellular Processes	[5]

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] CH5424802, a selective ALK inhibitor capable of blocking the resistant gatekeeper mutant. Cancer Cell. 2011 May 17;19(5):679-90.
• [4] In vitro metabolism of alectinib, a novel potent ALK inhibitor, in human: contribution of CYP3A enzymes. Xenobiotica. 2018 Jun;48(6):546-554.
• [5] 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.
• [6] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [7] 2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
• [8] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
• [9] 2017 FDA drug approvals.Nat Rev Drug Discov. 2018 Feb;17(2):81-85.
• [10] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [11] 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: 7397).
• [12] PF-06463922, an ALK/ROS1 Inhibitor, Overcomes Resistance to First and Second Generation ALK Inhibitors in Preclinical Models. Cancer Cell. 2015 Jul 13;28(1):70-81.
• [13] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
• [14] Treatment of ALK-positive non-small cell lung cancer. Arch Pathol Lab Med. 2012 Oct;136(10):1201-4.
• [15] Expression levels and activation of a PXR variant are directly related to drug resistance in osteosarcoma cell lines. Cancer. 2007 Mar 1;109(5):957-65.
• [16] Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
• [17] Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. J Pharmacol Exp Ther. 2004 Sep;310(3):1062-75.
• [18] Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
• [19] Metabolic interactions between acetaminophen (paracetamol) and two flavonoids, luteolin and quercetin, through in-vitro inhibition studies. J Pharm Pharmacol. 2017 Dec;69(12):1762-1772.
• [20] Potent mechanism-based inhibition of CYP3A4 by imatinib explains its liability to interact with CYP3A4 substrates. Br J Pharmacol. 2012 Apr;165(8):2787-98.
• [21] Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
• [22] The metabolism of zidovudine by human liver microsomes in vitro: formation of 3'-amino-3'-deoxythymidine. Biochem Pharmacol. 1994 Jul 19;48(2):267-76.
• [23] Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
• [24] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
• [25] Quercetin protected against isoniazide-induced HepG2 cell apoptosis by activating the SIRT1/ERK pathway. J Biochem Mol Toxicol. 2019 Sep;33(9):e22369. doi: 10.1002/jbt.22369. Epub 2019 Jul 23.
• [26] Drug-induced liver injury: Oltipraz and C2-ceramide intervene HNF-1/GSTA1 expression via JNK signaling pathway. J Appl Toxicol. 2021 Dec;41(12):2011-2020. doi: 10.1002/jat.4181. Epub 2021 May 6.
• [27] A Study of Gentianae Radix et Rhizoma Class Differences Based on Chemical Composition and Core Efficacy. Molecules. 2023 Oct 17;28(20):7132. doi: 10.3390/molecules28207132.