Featured New Products 2013

Highlighted products added to the Tocris Bioscience range during 2013

December 2013

Inhibits binding of ¹²⁵I-IP-10 and ¹²⁵I-ITAC to CXCR3 (IC₅₀ values are 8.0 and 8.2 nM respectively). Inhibits CXCR3-mediated cell migration by the chemokines IP-10, ITAC and MiG in vitro (IC₅₀ values are 8, 15 and 36 nM respectively).

Potent Raf kinase inhibitor

4836 | AZ 628

Potent, ATP-competitive inhibitor of Raf kinases (IC₅₀ values are 29, 34 and 105 nM for c-Raf1, B-Raf^V600E and wild-type B-Raf, respectively). Displays selectivity for Raf kinases over a panel of 150 other kinases. Also inhibits growth, and induces cell cycle arrest and apoptosis in colon and melanoma cell lines with the B-Raf^V600E mutation.

Potent protein kinase D (PKD) inhibitor

4975 | CRT 0066101

IC₅₀ values are 1, 2 and 2.5 nM for PKD1, PKD3 and PKD2 respectively. Exhibits selectivity for PKD against a panel of >90 protein kinases, including PKCα, MEK, ERK, c-Raf and c-Src. Orally bioavailable.

Tankyrase inhibitor

5049 | TC-E 5001

K_d values are 79 and 28 nM for TNKS1 and TNKS2 respectively; IC₅₀ = 33 nM for TNKS2. Devoid of activity at PARP1 and PARP2 (IC₅₀ >19 μM). Inhibits Wnt signaling and stabilizes Axin2 levels.

November 2013

Broad spectrum bromodomain inhibitor

4758 | Bromosporine

Accelerates FRAP recovery of BRD4 and CREBBP in cells at a concentration of 1 μM.

Potent and selective PI 3-Kβ inhibitor

4839 | AZD 6482

IC₅₀ values are 0.69, 13.6, 47.8 and 136 nM for PI 3-Kβ, PI 3-Kδ, PI 3-Kγ and PI 3-Kα, respectively. Selectively inhibits in vivo growth of the PTEN-deficient tumor xenografts HCC70 and PC3. Exhibits antithrombotic activity.

Fluorescent hydrogen peroxide indicator

4944 | Peroxy Orange 1

Displays an orange intracellular fluorescence in response to H₂O₂ signals produced in RAW 264.7 macrophages and A431 cells during immune response and growth factor stimulation, respectively. Cell permeable.

Potent Porcn inhibitor

4992 | IWP L6

EC₅₀ = 0.5 nM. Shown to inhibit Wnt-dependent processes such as tailfin regeneration and posterior axis formation in zebrafish; also reduces branching morphogenesis in cultured mouse embryonic kidneys.

Potent and selective ASIC1a blocker

5042 | Psalmotoxin 1

IC₅₀ = 0.9 nM. Displays no effect at ASIC1b, ASIC2a, ASIC3, heteromeric ASIC channels, ENaC and K_V2.1/2.2/4.2/4.3 channels expressed in oocytes, at concentrations up to 100 nM. Displays potent analgesic properties.

October 2013

LPA₅ receptor antagonist

4708 | TC LPA5 4

IC₅₀ = 0.8 μM in LPA₅-RH7777 cells. Inhibits LPA-induced aggregation of isolated human platelets. Exhibits selectivity for LPA₅ against 80 other screened targets.

MALT1 inhibitor

4848 | MI 2 (MALT1 inhibitor)

IC₅₀ = 5.84 μM. Irreversibly suppresses protease function. Decreases NF-κB activity induced by MALT1. Inhibits cell proliferation and MALT1-mediated cleavage activity. Suppresses human TMD8 and HBL-1 activated B cell-like diffuse large B cell lymphoma (ABC-DLBCL) tumor xenografts in mice and primary human ABC-DLBCLs ex vivo.

Selective S1P₃ receptor allosteric agonist

4897 | CYM 5541

EC₅₀ = 72-132 nM. Displays no activity at S1P₁, S1P₂, S1P₄ and S1P₅ receptors at concentrations up to 10 μM. Shows no significant activities in a profiling panel of 55 GPCRs, ion channels and transporters.

Inhibitor of KAT5 histone acetyltransferase

4903 | NU 9056

IC₅₀ values are < 2, 60, 36, and >100 μM for KAT5, p300, pCAF and GCN5, respectively. Inhibits protein acetylation in prostate cancer cell lines and blocks DNA damage response. Decreases proliferation of LNCaP cells; induces apoptosis via caspase activation.

Selective GPR55 antagonist

4959 | CID 16020046

Inhibits LPI-induced Ca²⁺ signaling (IC₅₀ = 0.21 μM in HEK-GPR55 cells), ERK1/2 phosphorylation and GPR55-mediated transcription factor activation. Decreases LPI-induced GPR55 internalization.

September 2013

Selective ADAM10 metalloprotease inhibitor

3995 | GI 254023X

Displays over 100-fold higher potency at ADAM10 compared to ADAM17. Blocks constitutive release of IL-6R, CX3CL1 and CXCL16 in cell-based cleavage experiments. Inhibits calcium ionophore-induced betacellulin shedding in IMPE cells.

Potent pan-Aurora kinase inhibitor

4584 | SNS 314 mesylate

IC₅₀ values are 3, 9 and 31 nM for Aurora C, A and B, respectively. Exhibits both in vitro and in vivo activity against human cancer cell lines and tumor xenograft models. Displays additive antiproliferative effects in combination with chemotherapeutics such as carboplatin (Cat. No. 2626), gemcitabine (Cat. No. 3259) and 5-fluorouracil (Cat. No. 3257).

Potent and selective ASK1 inhibitor

4825 | TC ASK 10

IC₅₀ = 14 nM. Displays selectivity for ASK1 over other kinases including ASK2 (IC₅₀ = 0.51 μM), MEKK1, TAK1, IKKβ, ERK1, JNK1, p38α, GSK-3β, PKCθ and B-raf (IC₅₀ values are > 10 μM). Blocks downstream JNK1/p38 phosphorylation in cells. Orally bioavailable.

Potent CREBBP/EP300 bromodomain inhibitor

4889 | SGC-CBP30

IC₅₀ values are 21-69 and 38 nM for CREBBP and EP300 bromodomains respectively. Displays over 40-fold selectivity for CREBBP over BRD4(1). Accelerates FRAP recovery in cells at a concentration of 1 μM.

Potent ROCK inhibitor

4927 | AS 1892802

IC₅₀ values are 52, 57 and 122 nM for human ROCK2, rat ROCK2 and human ROCK1 respectively by ELISA. Inhibits PKAC-α and PRKX (IC₅₀ values are 200 and 325 nM respectively). Exhibits analgesic effects in rat models of inflammatory (AIA) and noninflammatory (MIA) arthritic pain. Orally bioavailable.

August 2013

Potent α₂β₁ inhibitor; displays antithrombotic activity in vivo

4527 | TC-I 15

IC₅₀ values for the inhibition of human platelet adhesion to type I collagen are 12 and 715 nM for platelets under static conditions and under flow, respectively. Displays selectivity for α₂β₁ over α_vβ₃, α₅β₁, α₆β₁ and α_IIbβ₃ at concentrations exceeding 1000 nM. Reduces collagen IV production in mesangial cells. Active in vivo; prevents ferric chloride-induced clot formation in mice.

Potent Trk inhibitor; inhibits TrkA, TrkB and TrkC

4559 | GNF 5837

Displays antiproliferative effects in cellular Ba/F3 assays (IC₅₀ values are 7, 9 and 11 nM for cells containing the fusion proteins Tel-TrkC, Tel-TrkB and Tel-TrkA, respectively). Exhibits selectivity for Trk receptors over a range of kinases, with some activity at PDGFR and c-Kit (IC₅₀ values are 0.87 and 0.91 μM respectively). Orally bioavailable.

High affinity, non-peptide UT receptor antagonist

4667 | SB 706375

Non-peptide urotensin-II (UT) receptor antagonist (K_i values are 9.3, 19.1 and 20.7 nM for human, mouse and rat respectively). Displays ≥100-fold selectivity for the human UT receptor over 86 different receptors, ion channels, enzymes, transporters and nuclear hormones.

Selective Epac2 inhibitor

4844 | HJC 0350

IC₅₀ = 0.3 μM). Displays no effect on Epac1. Blocks stimulation of the Epac2-FL FRET sensor in HEK293 cells.

MCT1 and MCT2 inhibitor

4960 | AR-C155858

Inhibitor of the monocarboxylate transporters (MCTs) MCT1 and MCT2 (K_i values are 2.3 and <10 nM respectively). Exhibits no activity at MCT4.

July 2013

Dual irreversible inhibitor of ErbB2 and EGFR

3580 | HKI 357

IC₅₀ values are 33 and 34 nM respectively. Suppresses ligand-induced EGFR autophosphorylation and cell proliferation in NCI-H1975 cells containing L858R and T790M mutations. Circumvents mechanisms of resistance to Iressa (Cat. No. 3000) in non-small-cell lung cancer cells.

Potent MSK1 inhibitor

4630 | SB 747651A

IC₅₀ = 11 nM in an in vitro kinase assay. Targets the N-terminal kinase domain. Inhibits MSK1, MSK2, PKA, PKB, RSK and p70^S6K activity in cells. Blocks IL-10 production in macrophages.

Cdc42 inhibitor

4794 | ZCL 278

Targets the binding site of the Cdc42 guanine nucleotide exchange factor, intersectin (ITSN). Inhibits Cdc42-mediated cellular effects, including microspike formation in 3T3 fibroblasts and neuronal branching in primary neonatal cortical neurons. Also suppresses cell motility and migration in PC3 cells, without cytotoxic effects.

Potent FAAH inhibitor

4752 | SA 57

IC₅₀ < 10 nM. Inhibits both human and mouse FAAH enzymes; also inhibits mouse and human MAGL at higher concentrations (IC₅₀ values are 410 nM and 1.4 μM respectively). Also displays inhibitory activity against FAAH, MAGL and ABHD6 in vivo.

TRPC1 and TRPC6 blocker

4912 | GsMTx4

Inhibitor of the mechanosensitive TRP channels; also blocks stretch-activated cation channels in astrocytes, cardiac cells, and smooth and skeletal muscle cells.

June 2013

Potent Abl kinase inhibitor

4730 | PPY A

Inhibits T315l mutant and wild-type Abl kinases (IC₅₀ values are 9 and 20 nM, respectively). Inhibits growth of cells transformed with either the Bcr-Abl T315l mutant or wild-type Bcr-Abl gene.

Selective H₄ agonist

4769 | VUF 10460

Displays 50-fold selectivity for the rat H₄ receptor over the H₃ subtype (pK_i values are 5.75 and 7.46 for rat H₃ and H₄ receptors respectively). Also exhibits affinity for the human H₄ receptor (pK_i = 8.22).

Potent K_Ca3.1 channel blocker

4864 | NS 6180

IC₅₀ values are 9, 14 and 15 nM for rat, human and mouse erythrocyte K_Ca3.1 channels respectively. Exhibits ~ 50% inhibition of K_Ca1.1, K_V1.3, and K_V11.1 channels, norepinephrine and dopamine transporters, L-type Ca²⁺ channels and melatonin receptors at a concentration of 10 μM.

Potent and selective LPA₂ receptor antagonist

4878 | H2L5186303

IC₅₀ values are 8.9, 1230 and 27354 nM for lysophosphatidic acid 2 (LPA₂), LPA₃ and LPA₁ receptors respectively, in a LPA-elicited calcium mobilization assay.

Potent and selective Na_V1.8 channel blocker

4916 | PF 04885614

IC₅₀ = 53 nM for human Na_V1.8 channel. Exhibits selectivity for hNa_V1.8 over hNa_V1.6, hNa_V1.7, hNa_V1.1, hNa_V1.2 and hNa_V1.5 (IC₅₀ values are 4.2, 7.0, 11, 16 and 27 μM respectively). Orally bioavailable.

May 2013

Potent, selective CCR1 antagonist

3496 | BX 471

K_i = 1 nM for human CCR1. Exhibits 250-fold selectivity for CCR1 over CCR2, CCR5 and CXCR4. Inhibits MIP-α/CCL3-induced intracellular Ca²⁺ mobilization. Orally active; effectively reduces disease severity in a rat model of multiple sclerosis. Decreases renal fibrosis in a mouse model of obstructive nephropathy.

Potent, selective LRRK2 inhibitor

4629 | GSK2578215A

IC₅₀ values are 8.9 and 10.1 nM respectively for LRRK2[G2019S] mutant and wild-type LRRK2 respectively. Displays selectivity for LRRK2 against a panel of 460 other kinases. Blocks Ser910 and Ser935 phosphorylation in vitro and in peripheral tissues in vivo. Brain penetrant.

Mcl-1 inhibitor

4762 | MIM1

Selectively targets the BH3-binding pocket. Induces caspase-3/7 activation and cell death in Mcl-1-dependent leukemia cells. Also blocks Mcl-1-mediated suppression of tBID-induced Bax activation in vitro.

Potent and selective EP₂ receptor antagonist

4818 | PF 04418948

IC₅₀ = 16 nM for human EP₂ receptors. Displays over 2000-fold selectivity for EP₂ receptors over EP₁, EP₃, EP₄, DP₁ amd CRTH₂ receptors; exhibits <30% binding at a diverse panel of GPCRs and ion channels at a concentration of 10 μM. Inhibits PGE₂-induced increases in intracellular cAMP; reverses PGE₂-invoked relaxation of mouse trachea (IC₅₀ = 2.7 nM).

Tankyrase inhibitor

4855 | WIKI4

Inhibitor of Wnt/β-catenin signaling (EC₅₀ ~ 75 nM). Inhibits auto-ADP-ribosylation of tankyrase 2 (TNKS2) (IC₅₀ ~15 nM); prevents the ubiquitination and degradation of axin.

April 2013

Potent NK₁ receptor antagonist

4012 | SR 140333

K_i = 0.74 nM. IC₅₀ = 1.6 nM. Inhibits substance P-invoked calcium mobilization and outward current (IC₅₀ = 1.3 nM); blocks NK₁-mediated nitric oxide-dependent vasodilation in vivo.

Selective IKKα and IKKβ inhibitor

4547 | ACHP

IC₅₀ values are 8.5 and 250 nM for IKKβ and IKKα respectively. Selective for IKKα and IKKβ over IKK3, Syk and MAPKKK4 (IC₅₀ values are > 20 μM). Inhibits DNA binding activity of NF-κB. Blocks NF-κB pathway in multiple myeloma cell lines; induces cell growth arrest and apoptosis.

Potent and selective S1P₄ agonist

4677 | CYM 50260

EC₅₀ = 45 nM. Displays no activity at other S1P receptor subtypes (S1P_1-3 and S1P₅) at concentrations up to 25 μM.

Selective LPA₂ agonist; antiapoptotic

4779 | GRI 977143

EC₅₀ = 3.3 μM. Does not activate other LPA GPCRs at concentrations up to 10 μM. Antiapoptotic; inhibits activation of caspases 3, 7, 8 and 9, Bax translocation and PARP-1 cleavage. Activates ERK1/2 survival pathway.

ASIC3 channel blocker

4804 | APETx2

IC₅₀ values are 63 and 175 nM for homomeric rat and human ASIC3 channels, and 0.117, 0.9 and 2 μM for heteromeric rat ASIC3/2b, ASIC3/1b and ASIC3/1a channels, respectively. Displays no effect on homomeric ASIC1a, ASIC1b, and ASIC2a channels. Also inhibits Na_V1.8 channels (IC₅₀ = 2.6 μM). Analgesic.

March 2013

Highly potent and selective DOT1L inhibitor

4541 | SGC 0946

K_D = 0.06 nM, IC₅₀ = 0.3 nM in a radioactive assay; blocks H3K79 methylation in A431 cells and MCF10A cells (IC₅₀ values are 2.65 and 8.8 nM respectively). Selectively kills cells transformed with the MLL-AF9 fusion oncogene in an in vitro model of leukemia.

Selective S1P₁ agonist

4543 | CS 2100

EC₅₀ = 4.0 nM. Exhibits 5000-fold selectivity for human S1P₁ over S1P₃. Displays efficacy in a rat adjuvant-induced arthritis model.

Selective inhibitor of PI 3-Kinase γ

4674 | CZC 24832

IC₅₀ = 1.0 μM in a PI 3-Kγ-dependent fMLP-induced neutrophil migration assay. Exhibits limited off-target effects in kinome profiling of 154 identified lipid and protein kinases and 922 other proteins. Orally effective in a rodent model of inflammatory disease.

Potent and selective KSP inhibitor

4676 | ARRY 520 trifluoroacetate

Potent kinesin spindle protein (KSP) inhibitor (IC₅₀ = 6 nM); selective for KSP over >250 other receptors and kinases at a concentration of 10 μM. Induces degradation of Mcl-1; exhibits comparable cytotoxic activity to taxol (Cat. No. 1097) in epithelial ovarian cancer cells. Active in vivo.

Potent, selective Cdk4/6 inhibitor; brain penetrant

4786 | PD 0332991 isethionate

IC₅₀ values are 11 and 15 nM for Cdk4 and Cdk6 respectively. Selective for Cdk4/6 over a panel of 34 additional protein kinases (IC₅₀ values are > 10 μM). Induces G₁ cell cycle arrest and senescence in retinoblastoma protein (Rb)-proficient cell lines. Brain penetrant.

February 2013

Potent, selective BET bromodomain inhibitor

4499 | (+)-JQ1

IC₅₀ values are 17.7, 32.6, 76.9 and 12942 nM respectively for BRD2 (N), BRD4 (C), BRD4 (N) and CREBBP respectively. Induces squamous differentiation in NUT midline carcinoma (NMC) cell lines; inhibits tumor growth in NMC xenograft models in vivo. Exhibits reversible contraceptive effects in germ cells from male mice.

Highly potent and selective OX₂ antagonist; brain penetrant

4558 | EMPA

IC₅₀ values are 2.3 nM and 1900 nM for OX₂ and OX₁ respectively. Displays negligible or no inhibition of a panel of 80 receptors. Blocks orexin-B- and orexin-A-invoked calcium mobilization in hOX₂-expressing CHO cells (IC₅₀ values are 7.9 nM and 8.8 nM respectively); reverses orexin-B-induced hyperlocomotion in mice. Brain penetrant.

Potent and selective GPR120 agonist

4601 | TUG 891

pEC₅₀ values are 7.36 and 7.77 for human and mouse GPR120 respectively. Selective for GPR120 over free fatty acid receptors (pEC₅₀ = 4.19 for FFA1; displays no activity at FFA2 or FFA3). Cell permeable.

Potent inhibitor of interleukin-2 inducible T cell kinase (ITK)

4710 | PF 06465469

IC₅₀ = 2 nM. Also exhibits inhibitory activity against Bruton's tyrosine kinase (BTK) (IC₅₀ = 2 nM). Displays nanomolar potencies in a cell-based IP1 assay and human whole blood assay (IC₅₀ values are 31 and 48 nM respectively).

USP7 inhibitor

4733 | P005091

IC₅₀ = 4.2 μM. Displays little-to-no inhibition of other USP variants or proteases such as caspase, cathepsins and serine proteases; exhibits some activity at USP47. Induces elevated p53 and induces apoptosis in cancer cell lines; displays antiangiogenic activity in vivo.

January 2013

Potent and selective mTOR inhibitor

4282 | WYE 687

IC₅₀ = 7 nM. Displays selectivity for mTOR over PI 3-Kα (~100-fold) and PI 3-Kγ (~500-fold). Inhibits phosphorylation of mTORC1 and mTORC2 substrates including S6K, SGK and Akt; blocks VEGF secretion and HIF-1α expression. Exhibits antiproliferative effects in cancer cell lines through G₁ cell cycle arrest and selective apoptosis. ATP-competitive.

Potent and selective ERK2 inhibitor

4465 | TCS ERK 11e

K_i values are <2, 395, 540 and 852 nM for ERK2, GSK-3, Aurora Kinase A and Cdk2 respectively. Potently blocks proliferation of HT29 cells (IC₅₀ = 48 nM). Orally bioavailable.

Potent JAK inhibitor

4556 | CP 690550 citrate

IC₅₀ values are 1, 20, and 112 nM for JAK3, JAK2 and JAK1 respectively. Orally active immunosuppressant; exhibits efficacy in rodent rheumatoid arthritis models.

NPY Y₂ antagonist

4606 | CYM 9484

Potent neuropeptide Y (NPY) Y₂ receptor antagonist (IC₅₀ = 19 nM).

TRPC4 blocker

4732 | ML 204

IC₅₀ values are 0.96 and 2.6 μM in fluorescent and electrophysiological assays, respectively. Exhibits 19-fold selectivity against TRPC6 and 9-fold selectivity against TRPC5; displays no significant activity at TRPV1, TRPV3, TRPA1 and TRPM8 channels at concentrations up to 22 μM.