Featured New Products 2008

Highlighted products added to the Tocris Bioscience range during 2008

December 2008

mGlu₂ positive allosteric modulator

3283 | LY 487379

Potentiates glutamate-stimulated [³⁵S]GTPγS binding (EC₅₀ values are 1.7 and > 10 μM for mGlu₂ and mGlu₃ receptors respectively). Devoid of any activity at mGlu₅ and mGlu₇ receptors.

Potent and selective CRF₁ antagonist

3212 | CP 376395

K_i values are 12 and >10000 nM for CRF₁ and CRF₂ receptors respectively. Attenuates CRF-induced activation of the HPA axis in vivo following i.v. administration. Orally active.

Potent and selective FAK inhibitor

3239 | PF 573228

IC₅₀ = 4 nM. Displays 50-250-fold selectivity over other protein kinases. Blocks serum and fibronectin-directed migration and decreases focal adhesion turnover in vitro.

Highly selective NPY Y₁ receptor antagonist

IC₅₀ values are 0.38 and 0.72 nM at human and rat receptors respectively. Displays > 2600-fold selectivity over Y₂, Y₄ and Y₅ receptors. Inhibits NPY- and fasting-induced feeding in vivo following central administration.

Potent, positive allosteric mGlu₄ agonist

3248 | VU 0155041

EC₅₀ = 798 and 693 nM at human and rat mGlu₄ receptors respectively. Active in in vivo models of Parkinson"s disease following i.c.v. administration.

November 2008

Highly selective group II mGlu agonist

3246 | LY 354740

EC₅₀ values are 5.1 and 24.3 nM at mGlu₂ and mGlu₃ receptors respectively. Displays antianxiety and antiaddictive activity in vivo. Orally active.

Selective 5-HT₄ partial agonist

3089 | CJ 033466

Displays > 1000-fold selectivity for 5-HT₄ over other 5-HT and D₂ receptors. Exhibits gastroprokinetic effects in vivo following oral administration.

Selective, reversible FAAH inhibitor

3262 | JNJ 1661010

IC₅₀ = 12nM. Brain penetrant and active in vivo.

Potent TGF-βRI inhibitor

3269 | SD 208

Displays > 100 fold and > 17 fold selectivity over TGF-βRII and other common kinases respectively. Exhibits anti-inflammatory and antitumour activity.

Antiprion agent

3238 | TCS PrP Inhibitor 13

Potently inhibits protease-resistant prion protein (PrP-res) accumulation in two types of prion-infected mouse neuroblastoma (N2a) cell lines (IC₅₀ = 3nM).

October 2008

Selective 5-ht_5A antagonist

3188 | SB 699551

pK_i values are 8.3 for 5-ht_5A and < 6.0 for 5-HT_1B/D, 5-HT_2A, 5-HT_2C, 5-HT_1A and 5-HT₇ receptors.

Urotensin II (U-II) receptor antagonist

3162 | [Orn⁵]-URP

pEC₅₀ = 7.24. Displays no agonist activity unlike other U-II/URP analogues. Inhibits the action of U-II in the rat aorta ring assay.

Potent and selective 5-HT₆ antagonist

3189 | SB 399885

Displays > 200-fold selectivity for 5-HT₆over other 5-HT receptors (pK_i values are 9.11, 8.81 and 9.02 for human recombinant, native rat and native human 5-HT₆ receptors respectively).

Potent and selective MC₄R agonist

3032 | THIQ

IC₅₀ values are 1.2, 761 and 2067 nM for human MC₄R, MC₃R and MC₁R receptors respectively. Stimulates erectile activity in rats ex copula following systemic administration.

Selective 5-HT_1F agonist

3079 | LY 334370

K_i values are 1.87, 16.4, > 100 (IC₅₀), 176, 189 and 281 (IC₅₀) nM for 5-HT_1F, 5-HT_1A, 5-HT₄, 5-HT_1E, 5-HT_1B and 5-HT_1D receptors respectively. Displays antimigraine effects.

September 2008

Selective EGFR inhibitor

3000 | Iressa (Gefitinib)

Shows minimal activity against ErbB-2, KDR, c-flt, PKC, MEK and ERK-2. Blocks EGFR autophosphorylation and inhibits tumour growth in mice bearing a range of human xenografts.

High affinity 5-HT_2B antagonist

3077 | LY 272015

K_i values are 0.75, 21.63 and 28.7 nM for 5-HT_2B, 5-HT_2C and 5-HT_2A receptors respectively. Orally active.

Positive allosteric modulator of α7 nAChR

2995 | NS 1738

Exhibits no substantial activity for α4β2, α3β3 and α1-containing receptors. Displays cognitive-enhancing properties in vivo.

Selective V_1b agonist

3127 | d[Leu⁴,Lys⁸]-VP

K_ivalues are 0.16, 64, 100 and 3800 nM for V_1b, oxytocin, V₂ and V_1a receptors respectively. Displays weak antidiuretic, vasopressor and in vitro oxytocic activities.

Potent and selective inhibitor of iNOS

2866 | BYK 191023

IC₅₀ values are 86, 17000, 162000 nM for iNOS, nNOS and eNOS respectively). Acts in an NADPH- and time-dependent manner. Active in vivo, reverses pathological hypotension in the rodent endotoxin model.