Details of the Drug

General Information of Drug (ID: DMKM7EW)

Drug Name

PF-06463922

Synonyms

SCHEMBL15274056

Indication

Disease Entry	ICD 11	Status	REF
Non-small-cell lung cancer	2C25.Y	Phase 2	[1]
Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[2], [3]

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

406.4

Topological Polar Surface Area (xlogp)

1.5

Rotatable Bond Count (rotbonds)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

Chemical Identifiers

Formula: C21H19FN6O2
IUPAC Name: (16R)-19-amino-13-fluoro-4,8,16-trimethyl-9-oxo-17-oxa-4,5,8,20-tetrazatetracyclo[16.3.1.02,6.010,15]docosa-1(22),2,5,10(15),11,13,18,20-octaene-3-carbonitrile
Canonical SMILES: C[C@@H]1C2=C(C=CC(=C2)F)C(=O)N(CC3=NN(C(=C3C4=CC(=C(N=C4)N)O1)C#N)C)C
InChI: InChI=1S/C21H19FN6O2/c1-11-15-7-13(22)4-5-14(15)21(29)27(2)10-16-19(17(8-23)28(3)26-16)12-6-18(30-11)20(24)25-9-12/h4-7,9,11H,10H2,1-3H3,(H2,24,25)/t11-/m1/s1
InChIKey: IIXWYSCJSQVBQM-LLVKDONJSA-N

Cross-matching ID

PubChem CID: 71731823
ChEBI ID: CHEBI:143117
CAS Number: 1454846-35-5
DrugBank ID: DB12130
TTD ID: D04DYC
ACDINA ID: D01222

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]

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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease

Non-small-cell lung cancer

ICD Disease Classification

2C25.Y

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

Molecular Expression Atlas (MEA)

MEA Detail

Jump to Detail Molecular Expression Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Same Disease as PF-06463922

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Disease	REF
Brigatinib	DM7W94S	Major	Increased metabolism of PF-06463922 caused by Brigatinib mediated induction of CYP450 enzyme.	Lung cancer [2C25]	[14]
Lurbinectedin	DMEFRTZ	Major	Decreased metabolism of PF-06463922 caused by Lurbinectedin mediated inhibition of CYP450 enzyme.	Lung cancer [2C25]	[15]
Pralsetinib	DMWU0I2	Moderate	Increased metabolism of PF-06463922 caused by Pralsetinib mediated induction of CYP450 enzyme.	Lung cancer [2C25]	[16]
Selpercatinib	DMZR15V	Major	Increased metabolism of PF-06463922 caused by Selpercatinib mediated induction of CYP450 enzyme.	Lung cancer [2C25]	[17]
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Coadministration of a Drug Treating the Disease Different from PF-06463922 (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Gilteritinib	DMWQ4MZ	Moderate	Increased metabolism of PF-06463922 caused by Gilteritinib mediated induction of CYP450 enzyme.	Acute myeloid leukaemia [2A60]	[18]
Oliceridine	DM6MDCF	Major	Increased metabolism of PF-06463922 caused by Oliceridine mediated induction of CYP450 enzyme.	Acute pain [MG31]	[19]
Erdafitinib	DMI782S	Major	Increased metabolism of PF-06463922 caused by Erdafitinib mediated induction of CYP450 enzyme.	Bladder cancer [2C94]	[20]
Eslicarbazepine	DMZREFQ	Major	Increased metabolism of PF-06463922 caused by Eslicarbazepine mediated induction of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[21]
Bay 80-6946	DMLOS5R	Moderate	Increased metabolism of PF-06463922 caused by Bay 80-6946 mediated induction of CYP450 enzyme.	Follicular lymphoma [2A80]	[22]
Tazemetostat	DMWP1BH	Major	Increased metabolism of PF-06463922 caused by Tazemetostat mediated induction of CYP450 enzyme.	Follicular lymphoma [2A80]	[23]
Ripretinib	DM958QB	Moderate	Increased metabolism of PF-06463922 caused by Ripretinib mediated induction of CYP450 enzyme.	Gastrointestinal stromal tumour [2B5B]	[14]
Avapritinib	DMK2GZX	Major	Increased metabolism of PF-06463922 caused by Avapritinib mediated induction of CYP450 enzyme.	Gastrointestinal stromal tumour [2B5B]	[17]
MK-1439	DM215WE	Major	Increased metabolism of PF-06463922 caused by MK-1439 mediated induction of CYP450 enzyme.	Human immunodeficiency virus disease [1C60-1C62]	[17]
Pemigatinib	DM819JF	Major	Increased metabolism of PF-06463922 caused by Pemigatinib mediated induction of CYP450 enzyme.	Liver cancer [2C12]	[17]
Ubrogepant	DM749I3	Moderate	Increased metabolism of PF-06463922 caused by Ubrogepant mediated induction of CYP450 enzyme.	Migraine [8A80]	[24]
Rimegepant	DMHOAUG	Major	Increased metabolism of PF-06463922 caused by Rimegepant mediated induction of CYP450 enzyme.	Migraine [8A80]	[25]
Siponimod	DM2R86O	Major	Increased metabolism of PF-06463922 caused by Siponimod mediated induction of CYP450 enzyme.	Multiple sclerosis [8A40]	[14]
Fedratinib	DM4ZBK6	Major	Increased metabolism of PF-06463922 caused by Fedratinib mediated induction of CYP450 enzyme.	Myeloproliferative neoplasm [2A20]	[17]
Rucaparib	DM9PVX8	Moderate	Decreased metabolism of PF-06463922 caused by Rucaparib mediated inhibition of CYP450 enzyme.	Ovarian cancer [2C73]	[21]
Macimorelin	DMQYJIR	Moderate	Increased metabolism of PF-06463922 caused by Macimorelin mediated induction of CYP450 enzyme.	Pituitary gland disorder [5A60-5A61]	[26]
Lefamulin	DME6G97	Major	Accelerated clearance of PF-06463922 due to the transporter induction by Lefamulin.	Pneumonia [CA40]	[27]
Darolutamide	DMV7YFT	Major	Increased metabolism of PF-06463922 caused by Darolutamide mediated induction of CYP450 enzyme.	Prostate cancer [2C82]	[28]
Upadacitinib	DM32B5U	Moderate	Increased metabolism of PF-06463922 caused by Upadacitinib mediated induction of CYP450 enzyme.	Rheumatoid arthritis [FA20]	[29]
Voxelotor	DMCS6M5	Major	Increased metabolism of PF-06463922 caused by Voxelotor mediated induction of CYP450 enzyme.	Sickle-cell disorder [3A51]	[30]
Larotrectinib	DM26CQR	Moderate	Increased metabolism of PF-06463922 caused by Larotrectinib mediated induction of CYP450 enzyme.	Solid tumour/cancer [2A00-2F9Z]	[14]
Fluticasone	DMGCSVF	Moderate	Increased metabolism of PF-06463922 caused by Fluticasone mediated induction of CYP450 enzyme.	Vasomotor/allergic rhinitis [CA08]	[21]
Betrixaban	DM2C4RF	Moderate	Accelerated clearance of PF-06463922 due to the transporter induction by Betrixaban.	Venous thromboembolism [BD72]	[31]
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⏷ Show the Full List of 23 DDI Information of This Drug

References

1	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
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: 7476).
3	ClinicalTrials.gov (NCT01970865) A Study Of PF-06463922 An ALK/ROS1 Inhibitor In Patients With Advanced Non Small Cell Lung Cancer With Specific Molecular Alterations. U.S. National Institutes of Health.
4	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.
5	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
6	2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
7	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
8	2017 FDA drug approvals.Nat Rev Drug Discov. 2018 Feb;17(2):81-85.
9	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).
10	CH5424802, a selective ALK inhibitor capable of blocking the resistant gatekeeper mutant. Cancer Cell. 2011 May 17;19(5):679-90.
11	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
12	Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
13	Treatment of ALK-positive non-small cell lung cancer. Arch Pathol Lab Med. 2012 Oct;136(10):1201-4.
14	Cerner Multum, Inc. "Australian Product Information.".
15	Product Information. Zepzelca (lurbinectedin). Jazz Pharmaceuticals, Palo Alto, CA.
16	Product Information. Gavreto (pralsetinib). Blueprint Medicines Corporation, Cambridge, MA.
17	Cerner Multum, Inc. "UK Summary of Product Characteristics.".
18	Product Information. Xospata (gilteritinib). Astellas Pharma US, Inc, Deerfield, IL.
19	Canadian Pharmacists Association.
20	Product Information. Balversa (erdafitinib). Janssen Products, LP, Horsham, PA.
21	Product Information. Lorbrena (lorlatinib). Pfizer U.S. Pharmaceuticals Group, New York, NY.
22	Product Information. Aliqopa (copanlisib). Bayer Pharmaceutical Inc, West Haven, CT.
23	Product Information. Tazverik (tazemetostat). Epizyme, Inc, Cambridge, MA.
24	Product Information. Ubrelvy (ubrogepant). Allergan Inc, Irvine, CA.
25	Product Information. Nurtec ODT (rimegepant). Biohaven Pharmaceuticals, New Haven, CT.
26	Product Information. Macrilen (macimorelin). Aeterna Zentaris, Charleston, SC.
27	Product Information. Xenleta (lefamulin). Nabriva Therapeutics US, Inc., King of Prussia, PA.
28	Product Information. Nubeqa (darolutamide). Bayer HealthCare Pharmaceuticals Inc., Whippany, NJ.
29	Product Information. Rinvoq (upadacitinib). AbbVie US LLC, North Chicago, IL.
30	Product Information. Oxbryta (voxelotor). Global Blood Therapeutics, Inc., South San Francisco, CA.
31	Gelosa P, Castiglioni L, Tenconi M, et.al "Pharmacokinetic drug interactions of the non-vitamin K antagonist oral anticoagulants (NOACs)" Pharmacol Res 135 (2018): 60-79. [PMID: 30040996]