Table 1

Trk selective inhibitor AR786 is >1000 fold selective for TrkA over a diverse panel of kinases, receptors, channels and transporters

Kinases					CNS receptors	Nociceptive receptors
AKT1	Flt3	MAPKAP-K2	PKCα	SGK2	Adenosine A2A	Bradykinin B2
AKT2	Flt4	MAPKAP-K3	PKCβI	SGK3	Adenosine A3	Cannabinoid
AKT3	Fms	MAPKAP-K5	PKCβII	SIK	Adrenergic α1	CGRP1
ALK	Fyn	MARK1	PKCδ	SRC	Adrenergic α2	Opiate δ
ALK4	GRK5	MARK2	PKCε	SRPK1	Adrenergic β	Opiate κ
AMPK	GRK6	MEK1	PKCη	SRPK2	Androgen	Opiate µ
ARK5	GRK7	MELK	PKCγ	STK33	Dopamine D1	Phorbolester
AURKA	GSK3α	MKK7β	PKCι	Syk	Dopamine D3	Purinergic
Abl-P	GSK3β	MKNK2	PKCθ	TAK1	GABAA (flunitrazepam)	Tachykinin NK1
Abl2	HIPK1	MLK1	PKCζ	TAO1	GABAA (Muscimol)	Sigma
Ax1	HIPK2	MRCKα	PKD1	TAO2	GABAB	Inflammatory response
BLK_m	HIPK3	MRCKβ	PKD2	TAO3	Glutamate	1EP4
BTK	Haspin	MSK1	PRK2	TBK1	GPR103	Glucocorticoid
Bmx	Hck	MSK2	PRKG1α	TLK2	Imidazoline 12	Histamine H1
BrSK1	IGF-1R	MSSK1	PRKG1β	TNK2	Melatonin MT2	Histamine H2
BrSK2	IKKα	MST1	PTK5	TSSK1	Muscarinic (non-selective central)	Histamine H4
CAMK1	IKKβ	MST2	PTK6	TSSK2	Muscarinic oxotremorine	Leukotriene
CAMK1d	IR	MST3	PhKγ2	Tie2	Neuropeptide Y1	PAF
CAMK2b	IR Act	MYLK	Pim-1	Txk	Neurotensin	CNS transporters
CAMK2g	IRAK1	Mer	Pim-2	ULK2	Nicotine Acetylcholine	GABA
CAMK4	IRAK4	Met	Pim-3	ULK3	Nicotine Acetylcholine α1	Norepinephrine (NET)
CDK1/cyclinB	IRR	MuSK	Plk1	VRK2	Rolipram	Serotonin (SERT)
CDK2/cyclinA	ITK	NEK11	Plk2	WNK2	Serotonin 5-HT1A	Channels
CDK2/cyclinE	JAK2	NEK2	Plk3	WNK3	Serotonin 5-HT2B	Calcium Channel l-Type
CDK3/cyclinE	JAK3	NEK3	PrKX	Yes	Serotonin 5-HT3	Calcium Channel N-type
CDK5/p25	JNK1α1	NEK6	RIPK2	ZAP-70	Somatostatin sst5	Miscellaneous
CDK5/p35	JNK2α2	NEK7	ROCK-I	c-Raf	Thyroid Hormone	Endothelin
CDK6/cyclinD3	JNK3	NLK	ROCK-II	eEF-2K		EGF
CDK7/cyclinH/MAT1	KDR	PAK2	Ret	mTOR		VIP1
CDK9/cyclinT1	KIT	PAK3	Ron	mTOR/FKBP12
CHK1	LIMK1	PAK5	Ros	p38α
CHK2	LKB1	PAK6	Rse	p38β
CK1_v	1OK	PASK	Rsk1	p38δ
CK1δ	Lck	PDGFRα	Rsk2	p38γ
CK1γ1	Lyn	PDGFRβ	Rsk3	p790S6K
CK1γ2	MAP3K5	PDK1	Rsk4
CK1γ3	MAP4K2	PKACα	SGK

The TrkA selective inhibitor AR786 demonstrated sub-nanomolar cellular inhibition of TrkA (IC50=0.6 nM) and >1000 fold selectivity over TrkB (IC50=1147 nM), and TrkC (IC50=1834 nM). AR786 exhibited a high level of selectivity over a panel of kinases run at the ATP Km at 1.0 and 10 nM compound concentrations respectively as well as a panel of non-kinase receptors and ion channels run at a 10 nM compound concentration. CNS, central nervous system; TrkA, tropomyosin receptor kinase A.