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.