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Details

Stereochemistry ACHIRAL
Molecular Formula C22H21ClFN3O3S
Molecular Weight 461.937
Optical Activity UNSPECIFIED
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of MK-5108

SMILES

OC(=O)[C@@]3(CC1=NC(NC2=NC=CS2)=CC=C1)CC[C@@H](CC3)OC4=CC=CC(Cl)=C4F

InChI

InChIKey=LCVIRAZGMYMNNT-VVONHTQRSA-N
InChI=1S/C22H21ClFN3O3S/c23-16-4-2-5-17(19(16)24)30-15-7-9-22(10-8-15,20(28)29)13-14-3-1-6-18(26-14)27-21-25-11-12-31-21/h1-6,11-12,15H,7-10,13H2,(H,28,29)(H,25,26,27)/t15-,22-

HIDE SMILES / InChI

Description
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/20053775

MK-5108 is a small molecule inhibitor of AuroraA kinase with high selectivity versus Aurora-B and C. It was tested in phase I study against advanced or refractory solid tumors both as a monotherapy or in combination with docetaxel, but this study was terminated early due to toxicities at MK-5108 doses below the anticipated PK exposure target.

Originator

Curator's Comment: Drug VX-689 was developed by Vertex Pharmaceuticals and licensed to Merck in 2009

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
0.064 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
50.2 μM
1800 mg 1 times / day multiple, oral
dose: 1800 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
MK-5108 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
25 μM
1200 mg 1 times / day multiple, oral
dose: 1200 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
MK-5108 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
28.9 μM
1500 mg 1 times / day multiple, oral
dose: 1500 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
MK-5108 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
4.8 μM
200 mg 1 times / day multiple, oral
dose: 200 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
MK-5108 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
11 μM
400 mg 1 times / day multiple, oral
dose: 400 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
MK-5108 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
20 μM
800 mg 1 times / day multiple, oral
dose: 800 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
MK-5108 plasma
Homo sapiens
population: UNHEALTHY
age: UNKNOWN
sex: FEMALE / MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
324.4 nM × h
1800 mg 1 times / day multiple, oral
dose: 1800 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
MK-5108 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
115.9 μM × h
1200 mg 1 times / day multiple, oral
dose: 1200 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
MK-5108 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
130.7 μM × h
1500 mg 1 times / day multiple, oral
dose: 1500 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
MK-5108 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
31.2 μM × h
200 mg 1 times / day multiple, oral
dose: 200 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
MK-5108 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
75.7 μM × h
400 mg 1 times / day multiple, oral
dose: 400 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
MK-5108 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
95.5 μM × h
800 mg 1 times / day multiple, oral
dose: 800 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
MK-5108 plasma
Homo sapiens
population: UNHEALTHY
age: UNKNOWN
sex: FEMALE / MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
6.6 h
1800 mg 1 times / day multiple, oral
dose: 1800 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
MK-5108 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
8.3 h
1200 mg 1 times / day multiple, oral
dose: 1200 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
MK-5108 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
11.4 h
1500 mg 1 times / day multiple, oral
dose: 1500 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
MK-5108 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
9.3 h
200 mg 1 times / day multiple, oral
dose: 200 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
MK-5108 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
8.7 h
400 mg 1 times / day multiple, oral
dose: 400 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
MK-5108 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
11.1 h
800 mg 1 times / day multiple, oral
dose: 800 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
MK-5108 plasma
Homo sapiens
population: UNHEALTHY
age: UNKNOWN
sex: FEMALE / MALE
food status: UNKNOWN
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG



OverviewOther

Other InhibitorOther SubstrateOther Inducer

Drug as perpetrator​
PubMed

PubMed

TitleDatePubMed
MK-5108, a highly selective Aurora-A kinase inhibitor, shows antitumor activity alone and in combination with docetaxel.
2010 Jan
A phase I study of MK-5108, an oral aurora a kinase inhibitor, administered both as monotherapy and in combination with docetaxel, in patients with advanced or refractory solid tumors.
2016 Feb
Patents

Patents

Sample Use Guides

In a randomized phase I study of against advanced or refractory solid tumors MK-5108 was administered p.o. BID Q12h on days 1-2 in 14-21 day cycles either alone (200 to 1800 mg) or in combination (100 to 225 mg) with IV docetaxel 60 mg/m(2).
Route of Administration: Oral
Recombinant His-tagged human Aurora-A protein was expressed in Escherichia coli and was purified with HisTrap HP column (GE Healthcare). The Aurora-A assay reaction was conducted in the presence of 20 μmol/L ATP, 25 μmol/L Tetra-Kemptide [RRR(GLRRASLG)4R-NH2], 1.0 μCi per well [gamma-33P]-ATP, 0.1 ng per well Aurora-A in 50 mmol/L Tris-HCl (pH 7.4), 15 mmol/L Mg(OAc)2, and 0.2 mmol/L EDTA at 30°C for 40 min. To investigate the inhibition mode of MK-5108 for Aurora-A, the IC50 values of MK-5108 were determined in the presence of different concentrations of ATP. Then, the IC50 value was plotted as a function of ATP concentration to analyze the effect of ATP concentration on the IC50 value of MK-5108.
Name Type Language
MK-5108
Common Name English
MK 5108
Code English
VX-689
Code English
CYCLOHEXANECARBOXYLIC ACID, 4-(3-CHLORO-2-FLUOROPHENOXY)-1-((6-(2-THIAZOLYLAMINO)-2-PYRIDINYL)METHYL)-, TRANS-
Common Name English
MK5108
Code English
Code System Code Type Description
EPA CompTox
DTXSID901026054
Created by admin on Sat Dec 16 19:32:12 UTC 2023 , Edited by admin on Sat Dec 16 19:32:12 UTC 2023
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CAS
1010085-13-8
Created by admin on Sat Dec 16 19:32:12 UTC 2023 , Edited by admin on Sat Dec 16 19:32:12 UTC 2023
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PUBCHEM
24748204
Created by admin on Sat Dec 16 19:32:12 UTC 2023 , Edited by admin on Sat Dec 16 19:32:12 UTC 2023
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DRUG BANK
DB12556
Created by admin on Sat Dec 16 19:32:12 UTC 2023 , Edited by admin on Sat Dec 16 19:32:12 UTC 2023
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FDA UNII
H8J407531S
Created by admin on Sat Dec 16 19:32:12 UTC 2023 , Edited by admin on Sat Dec 16 19:32:12 UTC 2023
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ChEMBL
CHEMBL3182444
Created by admin on Sat Dec 16 19:32:12 UTC 2023 , Edited by admin on Sat Dec 16 19:32:12 UTC 2023
PRIMARY
NCI_THESAURUS
C90585
Created by admin on Sat Dec 16 19:32:12 UTC 2023 , Edited by admin on Sat Dec 16 19:32:12 UTC 2023
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