Details of the Drug

General Information of Drug (ID: DM6IYAT)

Drug Name

PMID28270010-Compound-Figure21-b

Indication

Disease Entry	ICD 11	Status	REF
Brain metastases	2D50	Patented	[1]

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)

0

Hydrogen Bond Donor Count (hbonddonor)

1

Hydrogen Bond Acceptor Count (hbondacc)

7

ADMET Property

Absorption Tmax: The time to maximum plasma concentration (Tmax) is 1.2 h [2]
Bioavailability: The bioavailability of drug is 81% [2]
Clearance: The apparent oral clearance of drug is 11 L/h [3]
Elimination: 48% of the single oral 100 mg dose was recovered in urine (<1% as unchanged) and 41% in feces (about 9% as unchanged) [3]
Half-life: The concentration or amount of drug in body reduced by one-half in 24 hours [2]
Metabolism: The drug is metabolized via the CYP3A4 and UGT1A4, with minor contribution from CYP2C8, CYP2C19, CYP3A5, and UGT1A3 [2]
Vd: The volume of distribution (Vd) of drug is 305 L [3]

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: D0N8YJ
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	[1]
Proto-oncogene c-Ros (ROS1)	TTSZ6Y3	ROS1_HUMAN	Inhibitor	[1]

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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

Brain metastases

ICD Disease Classification

2D50

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Proto-oncogene c-Ros (ROS1)	DTT	ROS1	1.45E-44	-1.01	-1.9
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

References

1	Tropomyosin receptor kinase inhibitors: an updated patent review for 2010-2016 - Part I.Expert Opin Ther Pat. 2017 Jun;27(6):733-751.
2	FDA approval: ado-trastuzumab emtansine for the treatment of patients with HER2-positive metastatic breast cancer. Clin Cancer Res. 2014 Sep 1;20(17):4436-41.
3	An FDA phase I clinical trial of quinacrine sterilization (QS). Int J Gynaecol Obstet. 2003 Oct;83 Suppl 2:S45-9.
4	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
5	2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
6	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
7	2017 FDA drug approvals.Nat Rev Drug Discov. 2018 Feb;17(2):81-85.
8	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).
9	CH5424802, a selective ALK inhibitor capable of blocking the resistant gatekeeper mutant. Cancer Cell. 2011 May 17;19(5):679-90.
10	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
11	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.
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	Clinical pipeline report, company report or official report of AnHeart Therapeutics.
14	National Cancer Institute Drug Dictionary (drug id 766123).
15	RET kinase inhibitors: a review of recent patents (2012-2015).Expert Opin Ther Pat. 2017 Jan;27(1):91-99.