Featured New Products 2017

Highlighted products added to the Tocris Bioscience range during 2017

June 2017

Potent and reversible NIMA related kinase 2 (Nek2) inhibitor

5150 | NCL 00017509

IC₅₀ = 56 nM. Induces increased mitotic abnormalities and mitotic delay. Cell permeable and active in vivo.

Potent and selective PFKFB3 inhibitor

IC₅₀ = 0.023 μM. Selective for PFKFB3 over PFKFB2 and PFKFB1 isoforms (IC₅₀ values are 0.382 μM and 2.06 μM, respectively). Reduces levels of fructose-1,6-bisphosphate in A549 cells (IC₅₀ = 0.343 μM). Exhibits no significant inhibition of other kinases.

Serine/threonine protein kinase 16 (STK16) inhibitor

6036 | STK16-IN-1

IC₅₀ = 295 nM. Reduces cell number and increases accumulation of binucleated MCF-1 cells. Enhances cell apoptosis in combination with chemotherapeutics. Also inhibits P1 3-Kδ and P1 3-Kγ kinases (IC₅₀ values are 856 and 867 nM, respectively) and mTOR kinase (IC₅₀= 5.56 μM).

Potent Ack1/TNK2 inhibitor

6061 | XMD 8-87

IC₅₀ = 38 and 113 nM in Ba/F3 cell lines containing leukemia-associated D163E and R806Q mutations, respectively. Blocks phosphorylation of TNK2 receptors containing solid-tumor type truncation mutations.

Plasminogen activator inhibitor-1 (PAI-1) inhibitor

6194 | TM 5441

IC₅₀ = 3.58 - 60.3 μM. Increases apoptosis in human cancer cell lines. Reduces senescence and increases lifespan in mouse models of ageing (kl/kl). Inhibits L-NAME (Cat.No. 0665) induced systolic blood pressure increases, telomere length reduction and hypertrophy in mice. Renoprotective. Orally bioavailable.

May 2017

α4β2 nAChR potent positive allosteric modulator

5963 | CMPI

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.

Potent bone morphogenetic protein type I (ALK) inhibitor

6151 | LDN 212854

IC₅₀ values are 1.3, 2.4, 85.8, 2,133 and 9,276 nM for ALK2, ALK1, ALK3, ALK4 and ALK5, respectively. Exhibits selectivity for ALK2 over ALK4 and ALK5 in cellular assays. Inhibits heterotopic ossification in a mutant ALK2 mouse model of fibrodysplasia ossificans progressiva. Also exhibits activity against RIPK2, ABL1 and PDGFR-β (IC₅₀ values < 100 nM).

PROTAC that selectively degrades BRD4 in cells

6154 | MZ 1

Cell penetrant Proteolysis Targeting Chimera (PROTAC) compound based on (+)-JQ1 (Cat.No. 4499), conjugated to a von Hippel-Lindau (VHL) ligand. Retains high affinity for BRD2, BRD3 and BRD4 bromodomains (K_d = 13-60 nM) but induces preferential degradation of BRD4 over BRD2 and BRD3 in cells at 10-100 nM concentrations. Exhibits potent cytotoxicity and profound antiproliferative effects in AML cell lines. Negative control cis MZ 1 also available.

High-affinity inhibitor of E3 ubiquitin ligase VHL

6156 | VH 298

K_d = 80-90 nM. Blocks interaction between VHL and HIF-α downstream of HIF-α hydroxylation, initiating hypoxic response. Results in time and concentration-dependent accumulation of hydroxylated HIF-α, and upregulates mRNA and protein levels of HIF target genes. Cell permeable. Negative control cis VH 298 also available.

Potent Na⁺/Ca²⁺ exchanger (NCX) inhibitor

6164 | SEA 0400

Inhibits NCX activity in canine cardiac sarcolemmal vesicles, rat cardiomyocytes, cultured neurons, astrocytes and microglia (IC₅₀ values are 90, 92, 33, 5 and 8.3 nM, respectively). Reduces infarct volumes and exhibits protective effects against myocardial ischemia in rats.

April 2017

High affinity pan-RAR antagonist

5758 | AGN 193109

K_d values are 2, 2 and 3 nM at RARα, RARβ and RARγ, respectively. Does not bind retinoic X receptors.

Potent DDHD2 inhibitor

5865 | KLH 45

IC₅₀ = 1.3 nM. Selective for DDHD2 over 40 other serine hydrolases, but does exhibit cross-reactivity with ABHD6. In vivo active. Increases brain triacylglycerol levels in mice.

Inhibitor of IL-1β post-translational processing

6107 | CP 424174

IC₅₀ = 210 nM. Inhibits the formation of mature IL-1β. Indirectly inhibits NLRP3. Active in vivo and orally bioavailable.

Photoactivatable cell permeable fluorescent dye

6149 | PA Janelia Fluor™ 549, SE

Supplied as NHS ester. Non-fluorescent until activated at 365 nm. Photochemical quantum yield of uncaging = 2.2%, with improved yield upon protein conjugation. Compatible with self-labeling tag systems. Suitable for single molecule tracking and super resolution microscopy in live cells. Can be multiplexed with PA Janelia Fluor™ 646, SE (Cat. No. 6150) to perform two-colour sptPALM in live cells. Cell permeable. Excitation maximum = 551 - 553 nm; emission maximum = 570 - 573 nm.

Potent and selective VCP allosteric inhibitor

6180 | NMS 873

IC₅₀ = 30 nM. Selective over all other AAA ATPases, HSP90 and kinases tested (IC₅₀ >10 nM). Activates the unfolded protein response (UPR), and modulates autophagosome maturation. Exhibits antiproliferative activity in cancer cells in vitro. Reduces VCP-sensitaisation to trypsin digestion.

March 2017

Stable photoreleaser of L-glutamate

5785 | MDNI-caged-L-glutamate

Rapidly and efficiently releases glutamate (Cat. No. 0218) when photolysed (350 - 365 nm excitation). Water soluble and stable at neutral pH, and pharmacologically inactive at neuronal glutamate receptors (up to 200 μM). 5.5 times more photosensitive than MNI-caged L-glutamate (Cat. No. 1490). Laser activation of MDNI-glu evokes a rapid increase in intracellular Ca²⁺ concentration in astrocytes.

Potent and selective PRMT5 inhibitor

5777 | GSK 591

IC₅₀ = 4 nM. Selective for PRMT5 over a panel of other PRMTs and lysine methyltransferases. Inhibits proliferation of mantle cell lymphoma (MCL) in vitro.

Potent CXCR2 antagonist

5872 | AZ 10397767

IC₅₀ = 1 nM. Attenuates oxaliplatin-induced NF-κB activation, increases oxaliplatin cytotoxicity, and potentiates oxaliplatin-induced apoptosis in AIPC cells. Reduces the numbers of infiltrating neutrophils into both in vitro and in vivo tumor models. Orally bioavailable.

Selective fluorescent VMAT2 substrate

5911 | FFN 200

Selectively traces exocytosis in dopaminergic neuronal cell culture and brain tissue. Excitation and emission maxima are 352 and 451 nm, respectively.

Highly potent and SAM-competitive EZH2 inhibitor

6169 | PF 06726304

IC₅₀ = 0.7 nM. Inhibits proliferation of Karpas-422 cells (non-Hodgkin's lymphoma) in vitro, halts tumor growth and reduces intratumoral H3K27Me3 levels in mice.

February 2017

Potent and selective S1P₁ receptor antagonist

5833 | Ex 26

IC₅₀ = 0.93 nM. Exhibits >3,000-fold selectivity for S1P₁ over S1P₂, S1P₃, S1P₄ and S1P₅. Induces lymphocyte sequestration in peripheral lymph nodes and upregulates S1P₁ receptor expression. Reduces disease severity in mice with EAE. Increases IFN-α production in stimulated dendritic cells in vivo.

Potent mTOR inhibitor

5955 | eCF 309

IC₅₀ = 15 nM. Exhibits >60-fold selectivity for mTOR over PI 3-kinases and is inactive against a panel of other kinases. Inhibits growth of ER-positive MCF7 breast cancer cells in vitro (EC₅₀ = 8.5 nM). Cell permeable.

Potent PAK4 inhibitor; orally available

6005 | PF 3758309

IC₅₀ = 1.3 nM; K_d = 2.7 nM. Inhibits proliferation and anchorage-independent growth of a panel of tumor cell lines in vitro. Suppresses growth of human HCT116 and A549 tumor cell xenografts in mice.

Potent glucokinase activator; orally bioavailable

6034 | AM 2394

EC₅₀ = 60 nM. Reduces plasma glucose levels in an oral glucose tolerance test in ob/ob mice.

Ketamine metabolite; lacks ketamine side effects

6094 | 2R,6R-Hydroxynorketamine

Enhances AMPA receptor-mediated excitatory post-synaptic potentials in the CA1 region of hippocampal slices. Decreases intracellular D-serine (a NMDA co-agonist) concentrations in PC-12 cells (IC₅₀ = 0.68 nM). Exerts antidepressant effects in mice.

January 2017

Potent BRD9/7 inhibitor

6000 | TP 472

K_d values are 33 and 340 nM, respectively. Exhibits >30-fold selectivity for BRD9 over other bromodomains except BRD7. Cell permeable and active in vivo

Raf kinase and VEGFR-2 inhibitor

6015 | RAF 265

Inhibits c-Raf, wild type B-Raf and mutant B-Raf (V600E). Cytotoxic in certain melanoma cells lines. Effects enhanced by protein kinase D3 inhibition, preventing reactivation of MAPK signaling and increasing caspase activity. Orally bioavailable.

Endogenous amylin, calcitonin, CGRP and adrenomedullin agonist

6030 | Amylin (rat)

pEC₅₀ values are 7.06-9.50 at hCT_a, 8.11 at rCT_a, 7.73-10.1 at hAMY1_a, 9.74 at rAMY1_a, 7.92 at hAMY1_b, 7.78-9.9 at hAMY_2a, 7.94 at hAMY_2b, 8.09-10.8 at hAMY_3a, 9.97 at rAMY and 8.19 at hAMY_3b receptors. Suppresses insulin-stimulated glucose uptake. Delays gastric emptying and promotes satiety. Active in vivo.

Potent soluble guanylyl cyclase (sGC) activator

6052 | BAY 58-2667

EC₅₀ = 6.4 nM. Binds heme-free sGC. Exhibits antihypertensive effects in vivo.

Oct4 activator; enhances iPSC reprogramming efficiency

6066 | OAC-2

Enhances iPSC reprogramming four-fold and accelerates the appearance of iPSC colonies in combination with 4F (Oct4, Sox2, c-Myc and Klf4). Also induces cardiomyocyte-like cells from human fibroblasts, as part of the 9C cocktail (CHIR 99021, A83-01, BIX 01294, AS83541, SC1, Y-27632, SU 16f, JNJ10198409 and OAC-2)