Table 2. Kinase targets for CNS indications: small molecules with preclinical in vivo efficacy data.

Kinase	Type	Disease indication	Example compounds	Refs
AMPK	S–T	Multiple sclerosis	Arasine	144
		Cerebral ischaemia	Compound C	145
CDK	S–T	Traumatic brain injury	Roscovitine	147
		Cerebral ischaemia	Flavopiridol and indolinone A	148,149
DAPK1	S–T	Acute brain injury	11-(3-imino-5,6-dihydrobenzo[h]cinnolin-2(3H)-yl)- N-(6-phenylpyridazin-3-yl)undecanamide	41,43
		Alzheimer’s disease	11-(3-imino-5,6-dihydrobenzo[h]cinnolin-2(3H)-yl)- N-(6-phenylpyridazin-3-yl)undecanamide	42
GSK3	S–T	Alzheimer’s disease	SB-216763	150
			AR-AO14418	150
			Lithium	150,151
			Indirubin-3′-monoxime	150
			Alsterpaullone	150
			Chir98014	150
			NP-12*	34
		Amyotrophic lateral sclerosis	AR-AO14418	26
		Bipolar disorder	Multiple 3-benzofuranyl-4-indolylmalemide	152
		Cerebral ischaemia	Compound 1	153
			Chir025*	154
			TDZD-8	30
			AR-AO14418	28
		Depression	NP031115*	32
		HIV-associated dementia	Valproic acid	155
		Parkinson’s disease	AR-AO14418	156
			Indirubin-3′-oxime ((E)-3-(hydroxyimino)-2,3′-biindolin- 2′-one)	156
		Neurocognitive deficits after cranial irradiation	SB-415286	157
			SB-216763	157
		Shock	TDZD-8	30
		Spinal cord injury	TDZD-8	31
		Traumatic brain injury	Lithium	158
JAK3	S–T	Amyotrophic lateral sclerosis	WHI-P131	159
JNK1, JNK2 and JNK3	S–T	Subarachnoid haemorrhage	SP600125	87
		Parkinson’s disease	SP600125	160
		Cerebral ischaemia	AS601245	86
MEK1 and MEK2	S–T	Behavioral disorders and drug abuse	SL 327	161
		Cerebral ischaemia	U0126	82
			PD-98059	162,163
		Traumatic brain injury	PD-98059	85
		Neuropathic pain	PD 198306	164
MLK1, MLK2 and MLK3	S–T	Excitotoxic injury	CEP-1347	165
		Hearing loss	CEP-1347	89
		Huntington’s disease	CEP-1347	90,166
			CEP-11004	90
		Motor neuron disease	CEP-1347	167
		Parkinson’s disease	CEP-5104, CEP-6331 and CEP-1347	94
MLCK	S–T	Cerebral vasospasm	ML-9	168
mTOR	Y	Autism	Rapamycin	169
		Huntington’s disease	Temsirolimus	170
		Tuberous sclerosis	Rapamycin	169
p38α MAPK	S–T	Alzheimer’s disease	MW01-2-069ASRM	58
		Amyotrophic lateral sclerosis	SB203580	59
		Cerebral ischaemia	SB203580	60
			SB239063	61; 62
		Neuropathic pain	FR167653	171
		Parkinson’s disease	SB239063	70
		Spinal cord injury	SB203580	172
		Cerebral ischaemia	VX-745	173
		Traumatic brain injury	SB203580	85
PKA	S–T	Alzheimer’s disease	H89	174
		Memory impairment	Halofantrine	175
		Morphine tolerance	KT 5270	176
		Neuropathic pain	Triterpene mixture	177
PKC	S–T	Alzheimer’s disease	GF-109203X	178
		Bipolar disorder	Tamoxifen	179
		Brain tumours	LY 333531	180
		Cerebral ischaemia	Staurosporine	181
			GF-109203X	178
			Ebselen	182
		Cerebral vasospasm	H-7 and calphostin C	183
			Cheleritrine and rottlerin	184
		Neuropathic pain	Staurosporine and calphostin C	181
		Opioid dependence	H-7	185
		Parkinson’s disease	Rottlerin	186
PLK2	S–T	Parkinson’s disease	BI2536	187
ROCK	S–T	Alzheimer’s disease	Y-27632	188
		Cerebral ischaemia	Fasudil and hydroxyfasudil	189, 190
		Multiple sclerosis	Fasudil	191
		Epilepsy	Y-27632	192
		Spinal canal stenosis	Fasudil	171
		Pain	Y-27632	193
		Spinal cord injury	Y-27632	194
SNRPE	S–T	Cerebral ischaemia	SB-699393	146
SRC	Y	Brain injury	PP-1	195
		Intracerebral haemorrhage	PP-2	196
TGFβR	Y	Glioblastoma	SX-007*	197

^*The structure has not been disclosed. AMPK, AMP-activated kinase; CDK, cyclin-dependent kinase; DAPK1, death-associated protein kinase 1; GSK3, glycogen synthase kinase 3; JAK3, Janus kinase 3; MAPK, mitogen-activated protein kinase; MEK, MAPK–ERK kinase; MLCK, myosin light chain kinase; MLK, mixed lineage kinase; mTOR, mammalian target of rapamycin; PKA, protein kinase A; PKC, protein kinase C; PLK2, polo-like kinase 2; ROCK, Rho-associated protein kinase; SNRPE, small nuclear ribonucleoprotein polypeptide E (also known as B-RAF); TGFβR, transforming growth factor-β receptor.