TABLE 3

Summary of clinical development of drug candidates targeting chemokine receptors

See Figs. 8–10 for structures of representative clinical candidates.

Receptor	Company	Compound	Affinity	Indication	Clinical Phase	Status
			nM
CCR1	Schering AG (Berlex)	BX 471	1.0	MS, Psoriasis endometriosis	II	No efficacy
CCR1	Millennium	MLN 3701		MS, Multiple myeloma	II	No longer reported
CCR1	Millennium	MLN 3897	2.3	RA, Multiple myeloma	II	No efficacy in RA
CCR1	Pfizer	CP-481,715	64	RA	II	No efficacy
CCR1	AstraZeneca	AZD4818	5.0	COPD	II	No efficacy
CCR1	ChemoCentryx/GSK	CCX354	1.5	RA	II	Ongoing
CCR1	Merck	C-4462		RA	II	No efficacy
CCR1	Merck	C-6448		MS	II	No efficacy
CCR2	Millennium	MLN 1202^{^a}		RA	II	No efficacy
CCR2	Millennium	MLN 1202^{^a}		Atherosclerosis, MS	II	Ongoing
CCR2	Incyte	INCB8696		MS, Lupus	I	No longer reported
CCR2	Incyte	INCB3284	3.7	RA, Type II diabetes	II	No longer reported
CCR2	ChemoCentryx	CCX915		MS	I	Terminated
CCR2	ChemoCentryx	CCX140	2.3	Diabetic nephropathy	II	Ongoing
CCR2	Merck	MK-0812	5.0	RA, MS	II	No efficacy
CCR2	Pfizer	PF-4136309		Pain	II	No longer reported
CCR2	BMS	BMS-741672		Diabetic neuropathy	II	Ongoing
CCR2	Johnson & Johnson	JNJ-17166864	20.0	Allergic rhinitis	II	No efficacy
CCR3	Pharmaxis	ASM8^{^b}		Asthma	II	Ongoing
CCR3	GlaxoSmithKline	GSK766994	10.0	Asthma and allergic rhinitis	II	No efficacy
CCR3	Dupont	DPC168	2.0	Asthma	I	Development halted
CCR3	BMS	BMS-639623	0.3	Asthma	I	Ongoing
CCR3	Novartis	QAP-642		Allergic rhinitis	I	Development halted
CCR3	AstraZeneca	AZD3778	8.1	Allergic rhinitis	II	No longer reported
CCR4	Amgen	KW-0761^{^a}		Oncology	II	Ongoing
CCR4	GSK	GSK2239633	10.0	Asthma	I	Ongoing
CCR5	Pfizer	UK-427,857 (Maraviroc)	3.0	RA	II	No efficacy
CCR5	Pfizer	UK-427,857 (Maraviroc)	3.0	AIDS	Approved	Registered Drug
CCR5	Schering-Plough	SCH-C	2.0	RA	II	No efficacy
CCR5	Schering-Plough	SCH-C	2.0	AIDS	I	Development halted
CCR5	Schering-Plough	SCH-D	0.45	AIDS	II	Development halted
CCR5	GlaxoSmithKline	GW2239633	3.0	AIDS	III	Development halted
CCR5	Incyte	INCB9471	3.1	AIDS	II	Development halted
CCR5	Progenics	Pro 140^{^a}		AIDS	II	Ongoing
CCR5	Tobira	TAK652 (cenicroviroc)	3.1^{^e}	AIDS	II	Ongoing
CCR5	AstraZeneca	AZD5672	0.26	RA	II	No efficacy
CCR5	Novartis	NIBR-6465	0.8	AIDS	I	Ongoing
CCR5	Sangamo	SB-728^{^c}		AIDS	II	Ongoing
CCR5	HGS	HGS004^{^a}		AIDS	I	Ongoing
CCR9	ChemoCentryx/GSK	CCX282/vercirnon	6.0	IBD, Crohn’s	III	Terminated
CXCR1/ CXCR2	Schering-Plough	SCH 527123	3.9	COPD	II	Ongoing
CXCR1/ CXCR2	Schering-Plough	SCH 527123	0.049	COPD	II	Ongoing
CXCR1/ CXCR2	Dompé	Reparixin	1.0 (CXCR1)	Pancreatic islet transplantation	III	Ongoing
CXCR1/ CXCR2	Dompé	Reparixin	100 (CXCR2)	Pancreatic islet transplantation	III	Ongoing
CXCR2	GlaxoSmithKline	SB-656933	5.1	COPD, Cystic fibrosis	I	Ongoing
CXCR2	GlaxoSmithKline	GSK-1325756B		COPD?	I	Ongoing
CXCR2	AstraZeneca	AZD-5069		Bronchiectasis	II	Ongoing
CXCR3	Amgen	AMG487	8.0	Psoriasis	II	No efficacy
CXCR4	Genzyme/Sanofi-Aventis	Plerixafor (AMD3100)	74	Stem cell mobilization for transplantation in cancer (MM, Non-Hodgkins lymphoma)	Approved	Registered Drug
CXCR4	TaiGen	Burixafor		Stem cell transplantation	II	Ongoing
CXCR4	Polyphor	POL6326		Stem cell transplantation	II	Ongoing
CXCR4	Medarex	MDX-1338^{^a}		Multiple myeloma	I	Ongoing
CXCR4	Biokine	BKT140^{^d}		Stem cell transplantation	I	Ongoing

IBD, inflammatory bowel disease; MM, multiple myeloma; RA, rheumatoid arthritis.
↵^a Neutralizing monoclonal antibodies.
↵^b Antisense oligonucleotide.
↵^c Zinc finger nuclease;
↵^d Peptide.
↵^e Also has potent antagonist activity at CCR2.