Table 3.

Summary of p38^MAPK inhibitors that have reached clinical trials^a,^b

Inhibitorc	Company	Disease indication	Phase	Adverse effects and comments
AMG-548	Amgen	COPDd, RAd	I	Elevated liver enzymes.
ARRY-797	Array Biopharma	ASe, Dental pain, RA	I/II	Aching, conjunctival and ocular hyperaemia, dizziness, diarrhoea, headache, nausea.
ARRY-614	Array Biopharma	MDSe	I
AZD-6703	Astra Zeneca	RAd	I
AVE-9940	Sanofi-Aventis	RAd	I
BIRB796 (Doramapimod)	Boeringer Ingelheim	Crohn’s diseased, psoriasisd, RAd	II/III	Elevated liver enzymes, no efficacy in RA, some histological response in Psoriasis.
BMS-582949	Bristol-Myers Squibb	Atherosclerosise, psoriasis, RAe	II
GSK-681323 (SB-681323)	GlaxoSmithKline	COPD, neuropathic pain, patients with coronary heart disease undergoing percutaneous coronary interventions, RAe	II	Active RA trial is using [14C]SB-681323 preparation; trials with non-radioactive SB-681323 completed.
GSK-856553 (Iosmapimod)	GlaxoSmithKline	Atherosclerosise, COPDe, CVD, depression	II
GSK-610677	GlaxoSmithKline	COPD	I	Inhaled preparation. Dose escalation trial in healthy volunteers completed.
KC706	Kemia	RAc, metabolic disordersd, CVDd, pemphigus vulgarisd	II
PH-797804	Pfizer	COPDe, Neuropathic pain associated with post-herpetic neuralgia, RA	II
SC80036	Pfizer	RAd
PS-540446	Pharmacopoeia	Psoriasis, RA	I
RO4402257(Pamapimod)	Roche	RAd	II	No efficacy. Elevated liver enzymes, GI disorders, infection, RA flare, skin disorders.
RO3201195	Roche	RAd	I
RJW-67657	Johnson and Johnson	Inflammatory diseased	I
SCIO-469	Scios Inc, Johnson and Johnson	Dental pain, MDS, multiple myelomae, RAd	II	Cutaneous lesions, dizziness, light headedness, liver enzyme abnormalities. Some evidence for efficacy in dental pain.
SCIO-323	Scios Inc, Johnson and Johnson	Cerebral ischemiad, diabetesd, MDSd, RAd	I	Cutaneous lesions
TAK-715	Takeda	RAd	II
VX-745	Vertex	RAd	II	GI and liver toxicity, neurological problems in dogs
VX-702	Vertex	Acute coronary diseased, RAd	II	Infection, skin disorders, renal impairment

^aThe information was compiled from reviews cited in the text, www.clinicaltrials.gov and from company websites. Some data could be incomplete, reflecting the paucity of data from some trials.

^bAbbreviations: AS, ankylosing spondylitis; COPD, chronic obstructive pulmonary disease; CVD, cardiovascular disease; GI, gastrointestinal; MDS, myelodysplastic syndromes; RA, rheumatoid arthritis.

^cInhibitor targets: AMG-548, ARRY-797, ARRY-614, AZD-6703, AVE-9940, KC706, RO4402257, RO3201195, SCIO-469, SCIO-323, VX-745 and VX-702 used p38α; BIRB796 usedp38 α β γ and δ, and the specific isoform information is unknown for BMS-582949, GSK-681323, GSK-856553, GSK-610677, PH-797804, SC80036, PS-540446, RJW-67657 and TAK-715.

^dDiscontinued.

^eClinical trial currently active or recruiting patients.