Featured New Products 2016

Highlighted products added to the Tocris Bioscience range during 2016

December 2016

Potent fluorescent Smo antagonist

5561 | IHR-Cy3

IC₅₀ = 100 nM. Non fluorescent analog IHR 1 also available.

Potent and selective ERK5 inhibitor

5843 | AX 15836

IC₅₀ = 8 nM. Exhibits >1,000-fold selectivity for ERK5 over a panel of over 200 kinases. Also exhibits selectivity over bromodomain BRD4 (K_d = 3,600 nM).

Potent and selective PARG inhibitor; cell permeable

IC₅₀ = 26 nM. Exhibits >350-fold selectivity for PARG over a panel of ion channels, enzymes and receptors, including PARP1 and ARH3. Maintains PAR chains and induces DNA double stranded breaks in cells following DNA damage. Decreases colony formation of ZR-75-1 BRCA1 WT cells. Cell permeable.

Potent and selective BRD1 and TAF1 inhibitor

5970 | BAY 299

IC₅₀ values are 6 and 13 nM, respectively. Displays selectivity over other bromodomains (>30-fold over other members of the BRPF family; BRD9 and ATAD2; >300-fold over BRD4). Displays BRD1 and TAF1 inhibition in a NanoBRET cell assay.

Potent ALK2/3 inhibitor; promotes neural induction of hPSCs

6053 | LDN 193189

IC₅₀ values are 5 and 30 nM, respectively; inhibits BMP4-mediated Smad1/5/8 activation. Exhibits >200-fold selectivity for BMP signaling over TGF-β signaling. Also exhibits selectivity over AMPK, PDGFR and MAPK signaling. Promotes neural induction of hPSCs in combination with SB 431542 (Cat. No. 1614), SU 5402 (Cat. No. 3300), CHIR 99021 (Cat. No. 4423) and DAPT (Cat. No. 2634).

November 2016

Potent dual CRTH2 and prostaglandin D₂ (PGD₂) receptor antagonist

5701 | AMG 853

IC₅₀ values are 8 and 35 nM, respectively in plasma. Inhibits PGD₂-induced down modulation of CRTH2 on CD16^- granulocytes in human whole blood and PGD₂-induced cAMP response in platelets. Inhibits PGD₂-induced airway constriction in vivo. Orally bioavailable.

Potent and selective PFKFB3 inhibitor

5742 | AZ PFKFB3 67

IC₅₀ values are 11, 159 and 1130 nM for PFKFB3, PFKFB2 and PFKFB1 respectively.

Potent LPA₁ antagonist

5913 | Ro 6842262

IC₅₀ = 25 nM. Exhibits >1,200-fold selectivity for LPA₁ over LPA₃. Attenuates NHLF human lung fibroblast cell proliferation and contraction in vitro. Also reduces LPA-induced histamine plasma levels in mice. Orally bioavailable.

Potent and selective PI 3-kinase p110δ inhibitor

5919 | PI 3065

IC₅₀ = 5 nM; K_i = 1.5 nM. Exhibits >100-fold selectivity over p100α, p100γ and p100β isoforms (IC₅₀ values are 600, 910, >10,000 nM, respectively). Attenuates 4TI tumor growth and metastasis in vivo.

Potent δ-opioid receptor positive allosteric modulator

5983 | BMS 986187

EC₅₀ = 30 nM. Exhibits 100-fold selectivity for δ over μ-opioid receptor. Enhances affinity of [Leu⁵]-Enkephalin (Cat.No. 1889), SNC 80 (Cat.No. 0764) and TAN 67 (Cat.No. 0921) for the δ-opioid receptor.

October 2016

Potent Nek2 inhibitor

4546 | rac-CCT 250863

IC₅₀ = 73 nM. Exhibits selectivity for Nek2 over PLK1, MPS1, Cdk2 and Aurora A.

Negative allosteric modulator at mGlu₇; brain penetrant

5715 | (±)-ADX 71743

IC₅₀ = 300 nM. Blocks high frequency-induced LTP at SC-CA1 synapses in hippocampal slices in vitro. Increases evoked excitatory postsynaptic currents (eEPSCs) in mice. Brain penetrant.

Potent TMEM16A (Anoctamin-1) blocker

5770 | MONNA

IC₅₀ = 80 nM. Exhibits >100-fold selectivity for TMEM16A over bestrophin-1, CLC2 and CFTR. Induces vasorelaxation of rodent resistance arteries in presence or absence of chloride ions.

Selective noradrenalin and dopamine fluorescent indicator

5905 | Neurosensor 521

Exhibits selectivity over adrenalin, glycine and glutamate. Enables visualization of noradrenalin and dopamine in fixed and live cells. Excitation wavelength 488 nm, emission 521 nm.

Selective myeloperoxidase (MPO) inhibitor

6004 | PF 06281355

IC₅₀ = 1.5 μM in LPS-stimulated human whole blood. Selective for MPO over a panel of 50 receptors, enzymes, ion channels and transporters, including thyroid peroxidase. Inhibits MPO activity in peritoneal lavage and plasma in a murine peritonitis model. Also reduces lung edema in a murine pulmonary immune complex vasculitis model. Orally bioavailable.

September 2016

High affinity and selective P2Y₁₄ antagonist

4862 | PPTN

K_B = 434 nM. Exhibits >10,000-fold selectivity for P2Y₁₄ over other P2Y receptors. Inhibits UDP-glucose and MRS 2690-induced porcine pancreatic artery contraction ex vivo. Also blocks UDP-glucose-induced chemotaxis of HL-60 leukemia cells in vitro.

Selective mIDH1 inhibitor; phenotypically lethal

5244 | TC-E 5008

K_i = 120-190 nM. Displays >60-fold selectivity for mIDH1 (found in ~75% of gliomas) over wild type IDH1. Also inhibits D-2-hydroxyglutaric acid in cells expressing mIDH1 (EC₅₀ = 2.4 μM). Does not display cytotoxicity towards non-cancerous human cells. Phenotypically lethal.

Potent cdk1/2 inhibitor

5654 | BMS 265246

IC₅₀ values are 6, 9 and 230 nM for cdk1, cdk2 and cdk4, respectively. Inhibits proliferation of HCT-116 colon cancer cells in vitro.

Potent and selective inhibitor of integrins α_vβ₃ and α_vβ₅

5870 | Cilengitide

IC₅₀ values are 4.1 and 70 nM for α_vβ₃ and α_vβ₅, respectively. Exhibits ~10-fold selectivity over gpIIb/IIIa. Increases endothelial monolayer permeability. Also exhibits antiangiogenic activity.

ADAM 17 (TACE) and MMP inhibitor; orally bioavailable

5960 | TMI 1

IC₅₀ values are 3, 4.7, 6.6, 8.4, 12, 26 and 26 nM for MMP-13, MMP-2, MMP-1, ADAM 17, MMP-9, MMP-7 and MMP-14, respectively. Suppresses TNF-α production in an acute LPS-mouse model. Reduces severity score in an in vivo model of rheumatoid arthritis. Displays selective cytotoxicity towards tumor cells and cancer stem cells in vitro. Induces tumor apoptosis in a breast cancer in vivo model. Orally bioavailable.

August 2016

Potent inhibitor of EGFR, ErbB2 and Abl receptor tyrosine kinases

4397 | AV 412

IC₅₀ values are 0.5-2, 19 and 41 nM, respectively. Also weak inhibitor of FLT1 and Src. Inhibits EGFR and ErbB2 autophosphorylation in vitro in NSCLC and T-47D breast cancer cell lines, respectively. Inhibits tumor growth of EGFR-overexpressing A431 and ErbB2 overexpressing BT-474 tumor xenografts in mice.

Potent P2Y₁₂ antagonist; cell permeable

5650 | SAR 216471

IC₅₀ = 17 nM. Displays antiplatelet and antithrombotic activity in vivo. Orally available.

Potent and selective type I PRMT inhibitor

5713 | MS 023

IC₅₀ values are 8, 8, 30, 83 and 119 nM for PRMT6, PRMT8, PRMT1, PRMT4 and PRMT3, respectively. Exhibits no significant activity against type II and III PRMTs, PKMTs, DNMTs, KDMs and reader proteins. Reduces global arginine asymmetric dimethylation levels in vitro.

Selective tryptophan 2,3-dioxygenase (TDO) inhibitor

5794 | LM 10

IC₅₀ values are 0.62 and 2 μM for human and mouse TDO, respectively. Exhibits selectivity for TDO over IDO, MAO-A, MAO-B, and a panel of receptors and transporters. Reduces growth of TDO-expressing P815 mastocytoma tumors in mice. Orally bioavailable.

Potent microsomal prostaglandin E synthase 1 (mPGES-1) inhibitor

5917 | PF 9184

PIC₅₀ values are 16.5 and 1080 nM for human and rat mPGES-1, respectively. Exhibits >6500-fold selectivity for mPGES-1 over COX-1 and COX-2. Inhibits IL-1β-induced PGE₂ synthesis in vitro.

July 2016

Potent and selective BRD9 and BRD7 inhibitor; orally active

5590 | BI 9564

K_d values are 14 and 239 nM, respectively. Exhibits selectivity for BRD9/7 over 48 other bromodomains, 324 kinases and 55 GPCRs. Inhibits proliferation of AML cell lines in vitro and reduces AML tumor xenograft growth in vivo. Cell permeable and orally active.

Nrf2 activator; inhibits Nrf2/Keap1 interaction

5707 | RA 839

K_d = 6 μM. Suppresses LPS-induced iNOS and nitric oxide expression in macrophages. Anti-inflammatory.

Potent and selective S1P₅ agonist

5766 | A 971432

EC₅₀ values are 4.1 and 5.7 nM in cAMP and GTPγS assays, respectively. Exhibits 60-fold selectivity over S1P₁, and >1,600-fold selectivity over S1P_2-4 and a panel of 129 kinases and 79 receptors. Improves blood-brain barrier integrity in vitro and reverses age-related cognitive decline in vivo. Orally available.

Potent TNKS1/2 inhibitor

5775 | AZ 6102

IC₅₀ values are 1 and 3 nM, respectively. Exhibits >100-fold selectivity for TNKS1/2 over PARP-1, PARP-2 and PARP-6. Inhibits Wnt signaling in DLD-1 cells (IC₅₀ = 5 nM). Exhibits moderate oral bioavailability.

Selective ASIC1a inhibitor; analgesic

5938 | Mambalgin 1

IC₅₀ values are 192 and 72 nM for human ASIC1a and ASIC1a/1b dimer, respectively. Binds to closed/inactive channel. Selective for ASIC1a over ASIC2a, ASIC3, TRPV1, P2X₂, 5-HT₃, Na_v1.8, Ca_v3.2 and K_v1.2 channels. Increases latency of tail and paw withdrawal in mouse tail-flick and paw-flick tests. Analgesic.

June 2016

High affinity and selective EP₄ antagonist

5327 | BGC 20-1531

K_i = 3 nM. Exhibits >2500-fold selectivity for EP₄ over EP₂ and EP₃. Also selective over a range of other prostanoid receptors, ion channels, transporters and enzymes. Inhibits PGE₂-induced vasodilation of middle cerebral and meningeal arteries in vitro, and carotid blood flow in vivo. Orally bioavailable.

High affinity and selective HNE1 inhibitor

5651 | ONO 6818

K_i =12 nM. Exhibits >100-fold less activity at other related proteases including trypsin, pancreatic elastase, collagenase and murine macrophage elastase. Inhibits NA-induced lung hemorrhaging and suppresses leukocyte levels in an in vivo model of COPD. Orally active.

Oct3/4 inducer

5664 | O4I2

Promotes Oct3/4 expression and stabilizes the Oct3/4 protein in HEK293 cells. Induces expression of the pluripotent-associated genes Lin28, Sox2 and Nanog, and suppresses Rex1. Induces a 15-fold increase in Oct3/4 expression in human primary fibroblasts.

LSD1 inhibitor

5714 | S 2101

IC₅₀ = 990 nM; K_i = 610 nM. Exhibits selectivity for LSD1 over MAO-B and MAO-A (K_i values are 17 and 110 μM, respectively).

Potent and selective PI 3-kinase β inhibitor

5832 | TGX 221

IC₅₀ values are 0.007, 0.1, 3.5 and 5 μM for β, δ, γ and α isoforms, respectively. Shows >1,000-fold selectively for PI 3-kinase β over a range of other kinases. Inhibits thrombus formation in animal models.

May 2016

Potent TBK1 inhibitor

5067 | MRT 68601

IC₅₀ = 6 nM. Inhibits the formation of autophagosomes in lung cancer cells.

Potent and selective SMYD2 inhibitor

5365 | LLY 507

IC₅₀ = 15 nM. Exhibits >100-fold selectivity for SMYD2 over 25 other methyltransferases including SMYD3, SUV420H1 and SUV420H2. Also exhibits selectivity over a panel of GPCRs, nuclear receptors and cytochrome P450 enzymes. Inhibits SMYD2-mediated p53 methylation in vitro. Also inhibits proliferation of a range of esophageal, liver and breast cancer cell lines.

Potent Nurr1 activator

5699 | IP7e

EC₅₀ = 3.9 nM. Delays onset and reduces severity of symptoms in mice with experimental autoimmune encephalomyelitis (EAE). Also suppresses NF-κB signaling. Brain penetrant and orally bioavailable.

High affinity and selective presynaptic CHT inhibitor

5725 | ML 352

K_i = 92 nM. Exhibits selectivity for CHT over dopamine, serotonin and noradrenaline transporters; acetylcholinesterase and cholineacetyltransferase; and a panel of 65 other GPCRs, ion channels and transporters.

CXCR4 allosteric agonist

5795 | ATI 2341

EC₅₀ = 194 nM. Induces chemotaxis in CXCR4-expressing cells in vitro. Mobilizes polymorphonuclear neutrophils (PMNs) and hematopoietic stem and progenitor cells (HSPCs) from bone marrow niche in vivo. Exhibits biased signaling towards G_i proteins over G₁₃ and β-arrestin.

April 2016

Potent Chk2 inhibitor

4968 | CCT 241533

IC₅₀ = 3 nM. Shows >63-fold selectivity for Chk1 over Chk2 and a panel of 84 other kinases. Inhibits Chk2 activation in response to etoposide-induced DNA damage in HT29 cells. Blocks ionizing radiation-induced apoptosis of mouse thymocytes.

High affinity and selective CB₂ inverse agonist

5039 | SR 144528

K_i = 0.6 nM. Exhibits >700-fold selectivity for CB₂ over CB₁ receptors. Blocks the effects of CP 55,940 (Cat. No. 0949) on forskolin-sensitive adenylyl cyclase activity and MAPK in CHO cells expressing CB₂ receptors. Also blocks CP 55,940-induced B-cell activation. Orally bioavailable.

Potent and selective CXCR2 antagonist

5660 | NVP CXCR2 20

IC₅₀ = 40 nM. Exhibits selectivity for CXCR2 over a panel of 49 other GPCRs. Orally bioavailable.

Potent and selective GPR139 agonist

5666 | JNJ 63533054

EC₅₀ = 16 nM. Selective for GPR139 over a panel of GPCRs, ion channels and transporters, including GPR142. Brain and cell penetrant. Orally bioavailable.

Selective CBP/p300 bromodomain inhibitor

5801 | PF CBP1

IC₅₀ values are 125 and 363 nM for CBP and p300, respectively. Exhibits >100-fold selectivity for CBP over BRD4. Also exhibits selectivity over a panel of other bromodomains. Reduces LPS-induced IL-1β, IL-6 and IFN-β expression in macrophages in vitro. Also downregulates RGS4 expression in primary cortical neurons in vitro.

March 2016

Potent and selective breast tumor kinase (Brk) inhibitor

5579 | Tilfrinib

IC₅₀ = 3.15 nM. Exhibits >1000-fold selectivity for Brk over a panel of other kinases. Inhibits proliferation of breast cancer cells in vitro.

Potent and selective dual mTORC1 and 2 inhibitor

5615 | AZD 3147

IC₅₀ = 1.5 nM. Exhibits >300-fold selectivity for mTOR over PI 3-kinase isoforms. Orally bioavailable.

Potent LXR antagonist

5694 | GSK 2033

pIC₅₀ = 7.5. Enhances T-cell proliferation and blocks T 0901317-antiproliferative activity on T-cells. Cell permeable.

Potent γ-secretase inhibitor

5751 | PF 3084014

IC₅₀ values are 1.2 and 6.2 nM in whole cell and cell-free assays, respectively. Reduces Aβ in brain, CSF and plasma in mice and guinea pigs.

High affinity 15-PGDH inhibitor

5759 | SW 033291

K_i = 0.1 nM. Increases PGE₂ levels in A549 cells in vitro, as well as in bone marrow, colon, lung and liver in mice. Promotes hematopoiesis, recovery from DSS-induced colitis, and hepatocyte proliferation after partial hepatectomy in mice.

February 2016

Potent and selective GRK2/3 inhibitor

5642 | CMPD101

Potent and selective GRK2/3 inhibitor (IC₅₀ values are 32 and 54 nM for GRK3 and GRK2, respectively). Exhibits selectivity for GRK2/3 over GRK1/5. Reduces DAMGO-induced desensitization and internalization of μ-opioid receptors.

OX₂ receptor antagonist; orally bioavailable

5645 | IPSU

OX₂ receptor antagonist. Exhibits approximately six-fold selectivity for OX₂ versus OX₁ receptors. Decreases activity and increases sleep time in mice during the active phase, without affecting REM/NREM balance. Orally bioavailable. Brain penetrant.

Potent and selective HDAC2/3 inhibitor

5647 | MI 192

Potent and selective HDAC2/3 inhibitor (IC₅₀ values are 16 and 30 nM, respectively). Exhibits >250-fold selectivity for HDAC2/3 over other HDAC isoforms. Promotes apoptosis of leukemia cell lines in vitro. Also attenuates IL-6 production in rheumatoid arthritis PBMCs in vitro.

Potent FXR antagonist

5656 | DY 268

Potent FXR antagonist (IC₅₀ = 7.5 nM). Exhibits no detectable cytotoxicity in cell-based assays.

MAP4K4 (HGK) inhibitor

5752 | PF 06260933

MAP4K4 (HGK) inhibitor (IC₅₀ = 140 nM). Also inhibits MINK and TNIK (IC₅₀ values are 8 and 13 nM, respectively). Improves fasting hyperglycemia in mice. Orally active.

January 2016

Potent stearoyl-CoA desaturase 1 inhibitor

4845 | A 939572

IC₅₀ = 0.4 nM. Selective for SCD1 over a range of kinases and hERG channels. Inhibits proliferation of squamous cell carcinoma FaDu cells in vitro. Also induces cell death of undifferentiated human embryonic stem cells (ESCs). Orally bioavailable.

Potent and selective NHE1 inhibitor

5512 | BIX NHE1 inhibitor

IC₅₀ = 31 nM. Selective for NHE1 over NHE2 and NHE3. Prevents ischemic damage in an ischemia reperfusion injury isolated rat heart model ex vivo. Prevents phenylephrine-induced cardiomyocyte hypertrophy in vitro, and attenuates cardiac hypertrophy and left ventricular dysfunction postinfarction in rats. Orally bioavailable.