cns penetrant

GSK805 is a potent, orally bioavailable and CNS-penetrant RORγt inhibitor.

Lu AF27139 is an effective and selective antagonist of P2X7 receptor (IC50s of 12 and 2.4 nM for human and rat, Kis of 22, 54, and 13 nM for mouse, human, and rat, respectively). Lu AF27139 can be used in CNS diseases studies.

VU6012962 is an orally bioavailable negative allosteric modulator of CNS-penetrant metabotropic glutamate receptor 7(mGlu7; IC50: 347 nM).

VU6005649 is an agonist of CNS penetrant mGlu7/8 receptor (EC50s: 0.65 μM and 2.6 μM for mGlu7 receptor and mGlu8 receptor, respectively).

VP3.15 dihydrobromide is a potent, orally bioavailable, and CNS-penetrant dual inhibitor of phosphodiesterase (PDE7) and glycogen synthase kinase (GSK)3, with IC50 values of 1.59 μM and 0.88 μM, respectively.

AT-007 is an orally active CNS penetrant Aldose Reductase inhibitor for the treatment of Galactosemia (IC50: 100 pM). It reduces toxic galactitol levels and prevents disease complications in GALT deficiency rats.

VP3.15 is an orally bioavailable and CNS-penetrant dual inhibitor of phosphodiesterase (PDE)7- GSK3 (IC50s: 1.59 μM and 0.88 μM for PDE7 and GSK-3).

VU0650786 is a selective and potent CNS-penetrant negative allosteric modulator of metabotropic glutamate receptor subtype 3 (mGlu3 NAM) (IC50: 392 nM), exhibiting antidepressant and anxiolytic activity in rodents.

XPC-6444 is a isoform-selective, and CNS-penetrant inhibitor of NaV1.6 with IC50 of41 nM for hNaV1.6,with anticonvulsant activity.

GLP-1R Antagonist 1 is an orally active, CNS penetrant and non-competitive glucagon-like peptide 1 receptor (GLP-1R) antagonist (IC50: 650 nM).

SB-222200 is a selective, reversible, and competitive antagonist of the human NK-3 receptor(Ki=4.4 nM).

SRX246 has no interaction at V1b and V2 receptors. SRX246 shows negligible binding at 64 other receptors classes, including 35 G-proteincoupled receptors. SRX246 is a potent and CNS-penetrant vasopressin 1a (V1a) receptor antagonist (Ki=0.3 nM for human V

ONO-2920632 is an orally active and CNS-penetrant TREK channel activator with EC50 values of 0.3 µM for TREK-1 and 2.8 µM for TREK-2. It demonstrates selectivity for other K2P channels, showing over 91-fold selectivity against TASK1, TASK2, TASK3, TRAAK, TWIK2, and 31-fold selectivity against TRESK. ONO-2920632 exhibits analgesic effects and is used in the study of pain, migraine, and neurological disorders.

ALK2-IN-6 (Compound 14a) is a and CNS-penetrant small molecule inhibitor target the activin receptor-like kinase 2 (ALK2/ACVR1) protein with a measured half-maximal inhibitory concentration (IC50) of 9 nM in biochemical assays.

ML289 (VU0463597) is a potent, selective, and CNS-penetrant negative allosteric modulator of mGlu3 (IC50=0.66 μM), with over 15-fold selectivity compared to mGlu2 and no activity against mGlu5.

PF-04781340 is an effective, selective, and CNS penetrant agonist of the 5-HT2C receptor.

PF-04781340 is an effective, selective, and CNS penetrant agonist of 5-HT2C receptor.

ML375 is a potent, selective and CNS penetrant M5 negative allosteric modulator (NAM).

ML380 is a highly potent and the first CNS penetrant M5 positive allosteric modulator (PAM).

PF-03463275 is an orally available, CNS-penetrant inhibitor of SLC6A9, a GlyT1 glycine transporter.

PF-06827443 is a orally bioavailable, CNS-penetrant M1-selective PAM with minimal agonist activity.

SB 235375 is a potent and selective antagonist of the neurokinin-3 receptor with low penetrance in the central nervous system (CNS).

Valiglurax (VU2957), also known as VU0652957 and VU2957, is a potent, selective, CNS penetrant, and orally bioavailable mGlu4 PAM. VU2957 possessed attractive in vitro and in vivo pharmacological and DMPK properties across species. VU2957 was evaluated as a preclinical development candidate for the treatment of Parkinson's disease.

Potent positive allosteric modulator of α4β2 nAChRs (EC50 values are 20 and 18 nM for rat and human, respectively). Selective for hα4β2 over hα3β2, hα3β4 and hα7. Inhibits (α4)2(β2)3, muscle-type and Torpedo nAChRs (IC50 values are 0.5, 0.7 and 0.2 μM, respectively), but not (α4)3(β2)2 receptors. Exhibits ability to photoincorporate into aliphatic and nucleophilic amino acid side chains. Hamouda (2016) Photolabeling a nicotinic acetylcholine receptor (nAChR) with an (α4)3(β2)2 nAChR-selective positive allosteric modulator. Mol.Pharmacol. 89 575 PMID:26976945 |Albrecht et al (2008) Discovery and optimization of substituted piperidines as potent, selective, CNS-penetrant α4β2 nicotinic acetylcholine receptor potentiators. Bioorg.Med.Chem.Lett. 18 5209 PMID:18789861 |Wang et al (2017) Unraveling amino acid residues critical for allosteric potentiation of (α4)3(β2)2-type nicotinic acetylcholine receptor responses. J.Biol.Chem. 292 9988 PMID:28446611