MK-0812

Investigational

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C24H36F3N3O2
Molecular Weight	455.5567
Optical Activity	UNSPECIFIED
Defined Stereocenters	4 / 4
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@]1(CC[C@](CN2CCC3=C(C2)C=C(C=N3)C(F)(F)F)(C1)C(C)C)N[C@H]4CCOC[C@H]4OC

InChI

InChIKey=UNVWTBOGMHPKJM-CWKRKGSWSA-N

InChI=1S/C24H36F3N3O2/c1-16(2)23(7-4-19(11-23)29-21-6-9-32-14-22(21)31-3)15-30-8-5-20-17(13-30)10-18(12-28-20)24(25,26)27/h10,12,16,19,21-22,29H,4-9,11,13-15H2,1-3H3/t19-,21+,22-,23-/m1/s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/24984897

MK-0812 is a potent and selective CCR2 antagonist, which was developed by Merck. This drug has entered clinical trials for both rheumatoid arthritis and multiple sclerosis. However, the rheumatoid arthritis trial was terminated because of lack of favorable outcomes when MK-0812 failed to show any early clinical improvement. The outcome of the multiple sclerosis trial of MK-0812 also had negative outcomes.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
C-C chemokine receptor type 2 17 Target ID: CHEMBL4015 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20004647	Antagonist 2778

Conditions

Condition	Modality	Targets	Highest Phase	Product
Arthritis 89 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20004647	Primary		Phase II 1132	Unknown Approved Use Unknown
Relapsing-remitting multiple sclerosis 10 Sources: https://clinicaltrials.gov/ct2/show/NCT00239655	Primary		Phase II 1132	Unknown Approved Use Unknown

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587	inhibitor 1767	inhibitor 1852

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	P-gp 1537

Drug as perpetrator

Target	Modality	Activity
CYP2C9 1819	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645842#sid=440681564	no
CYP3A4 1925	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645841#sid=440681564	no
CYP2D6 1891	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645840#sid=440681564	yes [IC50 16.933 uM]

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 1537	substrate 3367 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1346987#sid=363678186	no

Sourcing

Vendor/Aggregator	ID	URL
AA Blocks	AA00ECBJ	https://www.aablocks.com/goods/Goods/detail?id=AA00ECBJ
AK Scientific, Inc. (AKSCI)	Y0264	http://www.aksci.com/item_detail.php?cat=Y0264
AbMole Bioscience	M2156	http://www.abmole.com/products/mk-0812.html
Achemtek	0102-018093	http://www.achemtek.com/624733-88-6
Active Biopharma	ABP000347	http://www.activebiopharma.com/624733-88-6
Allbio Pharm Co., Ltd	AF08986	http://www.allbiopharm.com/product/n/AF08986
Ambinter	Amb22170000	http://www.ambinter.com/reference/22170000
Aurum Pharmatech LLC	W-5508	http://www.Aurumpharmatech.com/Product/ProductDetails/W_5508
BioCrick	BCC1755	http://www.biocrick.com/MK-0812-BCC1755.html
BioSynth	J-504013	https://www.biosynth.com/en/products/all-products/products/J-504013.html
Chem Scene	CS-0344	http://www.chemscene.com/624733-88-6.html
ChemShuttle	169486	http://www.chemshuttle.com/catalogsearch/result/?q=624733-88-6&cat=
Chemspace	CSSB00020618766	https://chem-space.com/CSSB00020618766
DC Chemicals	DC3167	http://www.dcchemicals.com/product_show-MK0812.html
Excenen	EX-A939	http://www.excenen.com/searchresultlist.php?id=624733-88-6
Lab Network	LN01342189	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01342189
MedChem Express	HY-50669	https://www.medchemexpress.com/mk-0812.html
MolPort	MolPort-021-804-973	https://www.molport.com/shop/molecule-link/MolPort-021-804-973
MuseChem	I004357	https://www.musechem.com/product/I004357.html
Renno Tech	RL04375	http://www.rennotech.com/product_show.asp?id=4624
Smolecule	S535602	http://www.smolecule.com/products/s535602
THE BioTek	bt-276043	https://www.thebiotek.com/product/inhibitors/bt-276043
THE BioTek	bt-464855	https://www.thebiotek.com/product/others/bt-464855
abcr GmbH	AB261951	http://www.abcr.com/shop/en/AB261951
eNovation Chemicals	D371895	http://www.enovationchem.com/productDetails.asp?productID=D371895
eNovation Chemicals	D548273	https://www.enovationchem.com/ProductDetails.asp?ProductID=D548273
eNovation Chemicals	D552130	https://www.enovationchem.com/ProductDetails.asp?ProductID=D552130

PubMed

Title	Date	PubMed
Assessment of chemokine receptor function on monocytes in whole blood: In vitro and ex vivo evaluations of a CCR2 antagonist.	2010 Jan 31	19913021
CC chemokine ligand 2 and CXC chemokine ligand 8 as neutrophil chemoattractant factors in canine idiopathic polyarthritis.	2016 Dec	27863550

Patents

Sample Use Guides

In Vivo Use Guide

MK0812 once daily for 12 weeks

Route of Administration: Oral

In Vitro Use Guide

MK0812 inhibited the binding of 125I-labeled recombinant human CCL2 to CCR2-containing mouse cell membranes with an IC50 of 19 nM in the presence of 97% mouse plasma. Similarly, MK0812 potently inhibited CCL2-mediated chemotaxis of WEHI-274.1 cells with an IC50 = 5 nM in the presence of 99% mouse plasma. The inhibition of WeHi-274.1 cell chemotaxis was tested with the concentrations of MK0812 (0.3 – 300 nM).

Name

Type

Language

MK-0812

Common Name

English

MK0812

Common Name

English

D-ERYTHRO-PENTITOL, 1,5-ANHYDRO-2,3-DIDEOXY-3-(((1R,3S)-3-((7,8-DIHYDRO-3-(TRIFLUOROMETHYL)-1,6-NAPHTHYRIDIN-6(5H)-YL)CARBONYL)-3-(1-METHYLETHYL)CYCLOPENTYL)AMINO)-4-O-METHYL-

Common Name

English

Code System Code Type Description

PUBCHEM

71587773