Table 1.

Small molecule JNK inhibitors identified in high throughput screening of proprietary chemical libraries

Core structure/Class description in initial publications	Inhibitor Structure (note: Compound number refers to that given in the original report)	Identification	IC50 (and/or Ki when reported)	PDB entry	Reference
Anthrapyrazolone	SP600125	High throughput screening of Celgene compound collection using JNK2 activity assay, followed by cell-based testing	IC50 JNK1 = 40 nM IC50 JNK2  = 40 nM IC50 JNK3 = 90 nM	1UKI 1PMV	[5]
Diaryl-imidazoles	Compound 1	Reported by scientists at Merck, but discovery approach not described. Note, this compound also interacts with and inhibits p38 with higher potency (IC50 p38 =  0.078 nM)	IC50 JNK3 = 7 nM	1PMN	[5]
(Benzoylaminomethyl) thiophene sulfonamides	Compound 50a	High throughput screening of Serono compound collection using JNK3 activity assay, followed by structure–activity relationship studies and neuronal cell based assays for the inhibition of NGF-deprivation-induced cell death.	IC50 JNK2 = 650 nM IC50 JNK3 = 150 nM	–	[58]
Dihydro-pyrrolo imidazoles	Compound (S)-5	Design by Eisai scientists based on structures of known p38 inhibitors with additions to increase JNK3 inhibitory potency and selectivity; testing inhibition of c-Jun phosphorylation and survival following K+ withdrawal from cerebellar granule neurons. Note, this compound inhibits p38 with lower potency (IC50 p38 = 28 nM)	IC50 JNK1 = 2.5 nM	–	[59]
(Benzothiazol-2-yl) acetonitrile	Compound 59 (AS601245)	High throughput screening of Serono compound collection using JNK3 activity assay, followed by structure–activity relationship studies, cell-based assays and anti-inflammatory effects in vivo.	IC50 JNK1 = 150 nM IC50 JNK2 = 220 nM IC50 JNK3 = 70 nM	–	[60]
Anilinoindazoles	Compound 10	High throughput screening of Astra Zeneca compound collection using JNK3 activity assay, followed structure–activity relationship studies.	IC50 JNK1 = 101 nM IC50 JNK3 = 3 nM	2B1P	[61]
Pyrazoloquinolinones	Compound 16	High throughput screening of Abbott compound collection using JNK1 activity assay, followed by testing in cell-based assays for inhibition of tumour necrosis-factor stimulated c-Jun phosphorylation	IC50 JNK1 = 290 nM	2GO1 (structure with a related compound)	[63]
Aminopyridines	Compound 35	High throughput screening of Abbott compound collection using JNK1 activity assay, followed by testing in cell-based assays for inhibition of tumour necrosis-factor stimulated c-Jun phosphorylation	IC50 JNK1 = 36 μM (Ki JNK1  = 3 nM) IC50 JNK2 = 70 μM (Ki JNK2  = 13 nM)(Ki JNK3 = 61 nM)	2GMX (structure with a related compound)	[64]
Pyridine carboxamide	Compound 12	High throughput screening of Abbott compound collection using JNK1 activity assay, followed by testing in cell-based assays for inhibition of tumour necrosis-factor stimulated c-Jun phosphorylation.	IC50 JNK1 = 24 nM) IC50 JNK2 = 74 nM)	2H96 (structure with a related compound)	[65]
Anilino-bipyridines	Compound 11	High throughput screening of Astra Zeneca compound collection using JNK3 activity assay, followed structure–activity relationship studies. Note, this compound also inhibits p38 with comparable potency (IC50 p38 = 40 nM)	IC50 JNK1 = 88 nM IC50 JNK3  = 15 nM	2EXC	[62]
Anilino-pyrimidines	Compound 2b	High throughput screening of Abbott compound collection using JNK1 activity assay, followed by rational structural design then testing in cell-based assays for inhibition of tumour necrosis-factor stimulated c-Jun phosphorylation.	IC50 JNK3 = 9 nM	2NO3	[66]