Featured New Products 2009

Highlighted products added to the Tocris Bioscience range during 2009

December 2009

Selective ERβ agonist

3366 | WAY 200070

Displays 68-fold selectivity over ERα (EC₅₀ values are 2 and 155 nM for ERβ and ERα respectively). Displays antianxiolytic and antidepressive effects in vivo.

Selective Rho-kinase (ROCK) inhibitor

IC₅₀ values are 14, 780 and 1940 nM for ROCK1, RSK and p70S6K respectively. Reverses adrenalin-induced contraction of the rat aortic ring (IC₅₀ = 190 nM) and causes a dose-dependent decrease in mean arterial blood pressure in spontaneous hypertensive rats. Orally active.

Selective positive allosteric modulator at mGlu₄

3707 | VU 0361737

EC₅₀ values are 240 and 110 nM at human and rat receptors respectively. Inactive at mGlu₁, mGlu₂, mGlu₃, mGlu₆ and mGlu₇ receptors and displays weak activity at mGlu₅ and mGlu₈ receptors. Brain penetrant.

Potent and highly selective GPR30 agonist

3577 | G-1

K_i = 11 nM, EC₅₀ = 2 nM. Displays no activity at ERα and ERβ at concentration up to 10 μM. Inhibits migration of SKBr3 cells and MCF-7 cells in response to chemoattractants (IC₅₀ values are 0.7 and 1.6 nM respectively) in vitro.

Potent DNA-dependent protein kinase inhibitor

3712 | NU 7441

IC₅₀ values are 14, 1700, 5000, >100000 and >100000 nM for DNA-PK, mTOR, PI 3-K, ATM and ATR respectively. Potentiates the effects of radiation, doxorubicin and etoposide in human tumor cell lines in vitro and etoposide in a human tumor xenograft model in vivo.

November 2009

Potent and selective CB₁ antagonist

3676 | PF 514273

K_i values are 1 and > 10000 nM at CB₁ and CB₂ receptors respectively. Inhibits food intake in vivo following oral administration.

Selective FGFR1 and -3 inhibitor

3044 | PD 173074

IC₅₀ values are 5, 21.5, ~100, 17600 and 19800 nM for FGFR3, FGFR1, VEGFR2, PDGFR and c-Src respectively. Inhibits VEGF- and FGF-induced angiogenesis in the mouse cornea model of angiogenesis.

Selective D₂-like agonist

3680 | Ropinirole

D₃ > D₂ > D₄. Causes biphasic spontaneous locomotor activity and contralateral circling in 6-OHDA-lesioned mice. Displays antiParkinsonian activity.

Benzodiazepine site agonist

3655 | Zaleplon

Non-benzodiazepine agent that acts as an agonist at the benzodiazepine site. Displays hypnotic, anxiolytic, myorelaxant and anticonvulsant activity.

Dual site Src kinase inhibitor

3642 | Src I1

IC₅₀ values are 44 and 88 nM for Src and Lck respectively. Can be used in parallel with PP 1 and PP 2 to inhibit Src family kinases.

October 2009

Potent, competitive NPY Y₁ antagonist

3242 | BMS 193885

K_i = 3.3 nM, IC₅₀ = 5.9 nM. Displays > 47, > 100, > 160, > 160 and > 160-fold selectivity over σ₁, α₁, Y₂, Y₄ and Y₅ receptors respectively. Reduces food intake and body weight via central Y₁ inhibition and is brain penetrant.

Peptide cleaved from PAR₁ upon receptor activation

3554 | Parstatin (mouse)

Cell-permeable peptide cleaved from protease-activated receptor 1 (PAR₁) upon receptor activation. Attenuates endothelial cell migration and proliferation (IC₅₀ ~ 20 μM), and induces cell cycle arrest.

Selective σ₁ antagonist

3133 | NE 100

K_i = 0.86 nM. Displays > 55-fold selectivity over σ₂ receptors and > 6000-fold selectivity over D₁, D₂, 5-HT_1A, 5-HT₂ and PCP receptors. Exhibits reversible binding (K_d = 1.2 nM) and displays antipsychotic activity in vivo. Orally active.

Reverse transcriptase inhibitor

3666 | Tenofovir

Selectively inhibits HIV reverse transcriptase (RNA-dependent DNA polymerase). Prevents cytotoxicity in SIV-infected C-8166 cells in vitro (IC₅₀ = 1.5 μM). Antiviral agent.

Potent and selective NPY Y₅ antagonist

3432 | S 25585

IC₅₀ values are 5.4, > 1000, > 10 000 and > 10 000 nM at Y₅, Y₁, Y₂ and Y₄ receptors respectively. Significantly inhibits NPY-induced feeding but not through blockade of Y₅ receptors.

September 2009

Potent, orally active DPP-IV inhibitor

3506 | NVP DPP 728

K_i = 11 nM, IC₅₀ = 14 nM. Displays > 15 000-fold selectivity over DPP-II and a range of proline-cleaving proteases. Exhibits antidiabetic activity in vivo.

Diacyl glycerolacyltransferase 1 (DGAT-1) inhibitor

3587 | A 922500

IC₅₀ values are 7 and 24 nM at human and mouse DGAT-1 respectively. Devoid of activity at DGAT-2, ACAT1 or ACAT2. Induces significant weight loss without altering food intake, and decreases liver and plasma triglyceride levels in vivo. Orally active.

Potent Raf kinase inhibitor

3185 | L-779,450

IC₅₀ = 10 nM. Displays > 7, > 30 and > 70-fold selectivity over p38α, GSK3β and Lck respectively. Suppresses DNA synthesis and induces apoptosis in cells that proliferate in response to Raf-1 and A-Raf but not B-Raf.

Selective FAAH inhibitor

3307 | PF 750

IC₅₀ = 16.2 nM. Displays no activity at a range of other serine hydrolases. Selectively inhibits FAAH within the central nervous system. Orally active.

Potent and selective CB₂ agonist

3088 | HU 308

K_i values are 22.7 nM and > 10 μM for CB₂ and CB₁ receptors respectively, EC₅₀ = 5.57 nM. Displays antiallodynic activity in the rat hindpaw incision model of postoperative pain.

August 2009

Potent and highly selective EP₃ antagonist

3342 | L-798,106

K_i values are 0.3, 916, > 5000 and > 5000 nM at EP₃, EP₄, EP₁ and EP₂ respectively. Attenuates sulprostone-induced inhibition of EFS-evoked twitch and contractile responses in vivo.

Orally active, selective 5-HT₆ antagonist

3368 | SB 271046

pK_i - 9.02 - 8.92. Increases extracellular glutamate and aspartate in the frontal cortex, and exhibits anticonvulsant activity (EC₅₀ = 0.16 μM).

SGK inhibitor

3572 | GSK 650394

IC₅₀ values are 62 and 103 nM for SGK1 and SGK2 respectively. Displays > 30-fold selectivity over Akt and other related kinases. Inhibits androgen-stimulated growth of LNCaP cells, a human prostate carcinoma cell line (IC₅₀ ~ 1 μM).

Potent AMPK activator

3336 | A 769662

EC₅₀ = 0.8 μM. Displays selectivity towards β1 subunit-containing heterotrimers. Inhibits fatty acid synthesis (IC₅₀ = 3.2 μM) and decreases plasma glucose and triglyceride levels in vivo.

GABA_A receptor positive allosteric modulator

3597 | Indiplon

K_i = 1.2 - 1.7 nM. Acts at the benzodiazepine site. Displays ~ 10-fold selectivity for α1 subunit-containing receptors. Exhibits sedative, hypnotic, anxiolytic and anticonvulsant activity in vivo and is orally active.

July 2009

Functionally selective M₁ agonist

3569 | Xanomeline

EC₅₀ values are 0.3, 5, 42, 52 and 92.5 nM at M₁, M₃, M₅, M₄ and M₂ receptors respectively. Exhibits antipsychotic activity, and improves cognitive deficits and behavioural disturbances in Alzheimer's disease and schizophrenia.

Potent and selective amylin receptor antagonist

3419 | AC 187

IC₅₀ = 0.48 nM. Displays 38-fold and 400-fold selectivity over calcitonin and CGRP receptors respectively. Increases glucagon secretion, accelerates gastric emptying, alters plasma glucose levels and increases food intake in vivo.

Potent and selective GlyT1 inhibitor

3397 | LY 2365109

IC₅₀ values are 15.8 and > 30 000 nM at GlyT1 and GlyT2 respectively. Induces a dose-dependent elevation in CSF levels of glycine, and enhances acetylcholine and dopamine release in the striatum and prefrontal cortex respectively. Produces profound locomotor and respiratory impairments at higher doses.

Potent FGFR and VEGFR inhibitor

3300 | SU 5402

IC₅₀ values are 0.02, 0.03, 0.51 and > 100 μM at VEGFR2, FGFR1, PDGFRβ and EGFR respectively. Inhibits embryonic left-right determination and exhibits potent anticancer activity in vitro and in vivo.

P2X₇ allosteric modulator

3385 | GW 791343

Exhibits species-specific activity; acts as a negative allosteric modulator of human P2X₇ (pIC₅₀ = 6.9 - 7.2) and a positive allosteric modulator of rat P2X₇.

June 2009

Potent and selective PAR₂ agonist

3369 | AC 55541

pEC₅₀ = 6.7). Displays no activity at other PAR subtypes. Stimulates cell proliferation, PI hydrolysis and Ca²⁺ mobilization in vitro (pEC₅₀ values are 6.7, 5.9 and 6.6 respectively) and exhibits pronociceptive activity in vivo.

Selective, non-competitive AMPA antagonist

2932 | CP 465022

IC₅₀ = 25 nM in rat cortical neurons. Displays potent anticonvulsant activity. Also significantly blocks the persistent component of Na_v1.6 channel activity. Brain penetrant and orally active.

Potent, broad spectrum MMP inhibitor

2961 | Batimastat

C₅₀ values are 3, 4, 4, 6 and 20 nM for MMP -1, -2, -9, -7 and -3 respectively). Exhibits antiproliferative, anti-invasive and antimetastatic activity in human ovarian carcinoma xenografts in vivo.

Potent and selective ATM kinase inhibitor

3544 | KU 55933

K_i = 2.2 nM, IC₅₀ values are 13, 2500, 9300, 16600, >100000 and > 100000 nM at ATM, DNA-PK, mTOR, PI 3-K, PI 4-K and ATR respectively. Decreases viability of MCF-7, A549 and HCT116 cells and decreases p21^CIP1 levels in vitro.

Potent ErbB receptor family inhibitor

3352 | JNJ 28871063

IC₅₀ values are 21, 22 and 38 nM for ErbB4, EGFR and ErbB2 respectively). Displays potent growth inhibition of human cancer cell lines overexpressing ErbB2 in vitro (IC₅₀.

May 2009

Potent, selective mGlu₅ antagonist

2921 | MTEP hydrochloride

IC₅₀ = 5 nM in Ca²⁺-flux assay; K_i= 16 nM. Displays anxiolytic activity in vivo and is orally active.

Antiangiogenic. Heparanase inhibitor

2710 | OGT 2115

IC₅₀ = 0.4 μM). Displays no major inhibition of human cytochrome P450 isoenzymes (IC₅₀ > 30 μM). Exhibits antiangiogenic properties in vitro (IC₅₀ = 1 μM).

Voltage-independent, CFTR channel blocker

3430 | CFTR_inh 172

K_i = 300 nM. Blocks intestinal fluid secretion induced by cholera toxin and Escherichia coli and suppresses cyst growth in animal models of polycystic kidney disease. Orally active.

Potent and selective CK1ε and CK1δ inhibitor

3316 | PF 670462

IC₅₀ values are 7.7 and 14 nM for CK1ε and CK1δ respectively. Displays > 30 fold selectivity over 42 other common kinases. Attenuates methamphetamine-stimulated locomotion in vivo.

Potent P2X₇ receptor antagonist

3323 | AZ 10606120

K_D values are 1.4 and 19 nM at human and rat P2X₇ receptors respectively. Binds in a positive cooperative manner to sites distinct from, but coupled to, the ATP binding site and acts as a negative allosteric modulator.

April 2009

Selective protein kinase D inhibitor

3327 | CID 755673

IC₅₀ values are 0.182, 0.280, 0.227, >10, 15.3, 20.3, 40.5 and >50 μM at PKD1, PKD2, PKD3, PKC, CAK, PLK1, CAMKIIα and Akt respectively. Inhibits prostate cancer cell proliferation, migration and invasion in vitro.

Selective mGlu₁ antagonist

3060 | A 841720

Displays 34-fold selectivity over mGlu₅m (IC₅₀ values are 10 and 342 nM respectively). Exhibits analgesic effects; decreases mechanical allodynia in models of neuropathic pain. Also impairs cognitive function.

Potent and selective α7 nAChR agonist

3092 | PHA 543613

Displays selectivity over α3β4, α1β1γδ, α4β2 and 5-HT₃ receptors. Positively influences sensory gating and memory in in vivo models of schizophrenia. Orally active and brain penetrant.

Potent and selective γ-secretase inhibitor

2627 | L-685,458

IC₅₀ = 17 nM. Displays > 50-fold selectivity over a range of aspartyl, serine and cysteine proteases. Exhibits equal potency for inhibition of Aβ40 and Aβ42 peptides (IC₅₀ values are 48 and 67 nM respectively in human neuroblastoma cells).

Potent and selective OX₂ antagonist

3371 | TCS OX2 29

IC₅₀ = 40 nM. Displays > 250 fold selectivity over OX₁ and 50 other receptors, ion channels and transporters.

March 2009

Subtype-selective GABA_A partial agonist

3250 | L-838,417

Selectively binds to α1, α2, α3 and α5 subunits (K_i values are 0.79, 0.67, 0.67 and 2.25 nM respectively) but displays no efficacy at α1 (α1-sparing). Exhibits non-sedative anxiolytic, antinociceptive and anti-inflammatory activity in vivo.

Non-steroidal androgen receptor antagonist

3389 | Bicalutamide

IC₅₀ = 190 nM. Displays peripheral selectivity and does not effect serum levels of LH and testosterone. Exhibits potent anticancer activity in vivo.

Potent aromatase (CYP19) inhibitor

3388 | Anastrozole

IC₅₀ = 15nM. Displays no discernible effect on adrenocorticoid hormone synthesis. Reduces plasma estrogen levels and exhibits antitumor activity in vivo. Orally active.

JAK2, FLT3 and TrkA inhibitor

3395 | Lestaurtinib

IC₅₀ values are 0.9, 3 and > 25 nM for JAK2, FLT3 and TrkA respectively. Prevents STAT5 phosphorylation (IC₅₀ = 20 - 30 nM). Exhibits antiproliferative activity in vitro and is effective against myeloproliferative disorders in vivo.

Potent, selective p38α and p38β inhibitor

2999 | RWJ 67657

IC₅₀ values are 1 and 11 μM for p38α and p38β respectively. Displays no activity at p38γ, p38δ and a range of other kinases. Exhibits cardioprotective and anti-inflammatory activity in vivo. Orally active.

February 2009

Positive allosteric modulator at mGlu₅

3235 | CDPPB

EC₅₀ values are 10 and 20 nM for human and rat receptors respectively. Antipsychotic; reverses amphetamine-induced locomotor activity and amphetamine-induced deficits in prepulse inhibition in rats.

Selective GABA_B positive allosteric modulator

3313 | rac BHFF

Increases the potency and efficacy of GABA ( > 15-fold and > 149% respectively). Exhibits anxiolytic activity in vivo and is orally active.

Potent Chk1 inhibitor

3038 | TCS 2312

K_i = 0.38 nM, EC₅₀ = 60 nM. Enhances the cell killing activity of Gemcitabine (Cat. No. 3259) in breast and prostate cancer cell lines and displays antiproliferative effects in vitro.

Highly selective CXCR4 antagonist

3299 | AMD 3100

IC₅₀ values are 0.02 - 0.13 and > 25 μM for CXCR4 and all other chemokine receptors respectively. Switches inflammatory responses from Th2 to Th1 type and reduces airway hyperresponsiveness in a mouse model of asthma.

Selective Pim-1 kinase inhibitor

2979 | TCS PIM-1 1

IC₅₀ values are 50, > 20000 and > 20000 nM for Pim-1, Pim-2 and MEK1/2 respectively.