in vitro PHARMACOLOGY 2011 CATALOG - Cerep

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204 in vitro pharmacology 2011 catalog testing conditions ❚ binding, enzyme and cellular assays ❚ suggested testing Primary screening at 1-10 µM in duplicate (2 wells), follow-up for IC 50 /Ki or EC 50 determination (8 concentrations in duplicate (16 wells) when compound displays more than 50% inhibition of control value or 50% stimulation relative to control. For functional GPCR cellular assays: assessment of agonist and/or antagonist effects. ❚ sample size (including IC 50 /EC 50 follow-up studies) See table page 209. ❚ requested compound information To reduce the registration time and ensure that all the appropriate information is available to start the study in a shortest possible timeframe, please use Cerep compound submission form 1 or MS Excel file 2 , and provide the following compound information: Name (compound ID) / Batch # / Molecular weight 3 / Formula weight 4 / Stock concentration / Stock solvent / Quantity / Unit 5 / Form / Storage conditions / Solubility, as well as Plate ID / plate position for compounds delivered in plates, Comments 6 , and Quotation number. NOTE: Impurity and colored compounds might affect the results (compound color information is mentioned in the study report). General remarks: - If compound(s) are supplied as a stock solution in plate(s) (preferred format for any submission of 10 or more compounds), please leave columns 1 and 12 empty in a 96W plate. The 384W plate format is also acceptable with columns 1, 2, 23 and 24 empty. For any other plate format, please inquire. - If compound(s) are not soluble in 100% DMSO, please provide any useful information concerning the solubility of the compound. The following solvents are compatible with most of our assays: DMSO (Cerep standard), H 2 O, Methanol, Tris/HCl 10 mM pH 7.4. - Organic solvents such as acetone, chloroform, ether, acetonitrile, tetrahydrofuran and trifluoroacetic acid are not recommended as they will significantly affect the results from many in vitro assays, even at very low concentrations. Customized handling procedure of compounds can be accommodated, please inquire for pricing conditions. ❚ protocol A typical protocol for binding assays includes a minimum of 6-control wells (non-specific and total binding) with or without vehicle for solvent-soluble compounds, plus an 8-point dose-response of the relevant reference compound. The binding assays that are performed using an agonist radioligand are labeled as such in the assay description. This assay design should pick more easily the test compounds that are agonists. For radioligand binding assays, how should I choose between the agonist and the antagonist models when both are available? For some binding assays two models are available using either agonist or antagonist as radioligand. G-protein-coupled receptors have both high-affinity and low-affinity states that are bound differently by agonists and antagonists. Whereas the antagonists bind with an equal affinity to both affinity states, agonists bind poorly to the low affinity state of the receptor. Therefore, it is advisable to use an antagonist radioligand to evaluate the binding of antagonists knowing that this may fail to reveal the binding of agonists. On the other hand, an assay using an agonist radioligand is suitable to evaluate both agonists and antagonists. The testing of a compound in both assays and the comparison of its competition curves against each radioligand may provide information about its functional activity at the receptor. A typical protocol for enzyme and all cellular assays includes a minimum of 6-control wells (background, and maximal signal with and without vehicle) plus an 8-point dose-response of the relevant reference compound. What kind of information cellular functional GPCR assays can bring about my compounds? Most our cellular functional GPCR assays are designed to determine if compounds induce agonist-like and/or antagonist activity. Those assays also allow to detect allosteric modulators with a modified protocol. Please inquire. Finally, 10 assays are specifically designed to detect inverse agonists. For other targets, please inquire 1 Cerep compound submission form will be emailed to you with your quotation. A copy can be requested from sales@cerep.com, or downloaded from Cerep website: www. cerep.com/Catalog Online 2 Systematically required for studies of 10 compounds or more. 3 Molecular weight (MW) of free acid or base form. 4 Formula weight (FW) including salt form and/or hydrate form if applicable. 5 mg?, mL? 6 e.g. useful information such as sensitivity to light, stability or hygroscopicity issues.
205 The reference compound for each assay is listed in each assay description. The historical average IC 50 /EC 50 value is also shown in each assay description. Any of our assay protocols can be customized: Please inquire ❚ deliverables Percent inhibition (mean of replicates), individual values as percent of control, EC 50 or IC 50 value (calculated from a minimum 5 concentration testing), Ki value for receptor binding assays (calculated using Cheng-Prussof equation, and the true Kd of the membrane preparation used for the experiment), K Bapp for functional GPCR cellular assays, Hill coefficient (nH), and plotted EC 50 or IC 50 curves. NOTE: The Kd values mentioned in the catalog are indicative values only. ❚ data turnaround Complete data set is typically available within 3 weeks, after receipt of the compounds at the testing site, for all the binding assays and most of the enzyme assays (providing that we receive all available information to initiate the study). The cell-based assays (including the functional assays) would require 3 to 6 weeks for data delivery. Secure, password-protected data can be viewed on line as soon as they are produced, after scientific approval and QC-ed by an experienced technician. For majority of assays, ExpresScreen option (5 business day turnaround time) is available: please inquire. Cerep services Receptors Ion channels Transporters ❚ tissue assays ❚ suggested testing Qualitative screening Assessment of both agonism and antagonism at 3 concentrations in duplicate (2 tissues) Suggested test concentrations: 1, 3 and 10 times the IC 50 /K i binding value Catalog prices correspond to this combination. Follow-up testing for quantitative determination of pharmacological parameters EC 50 /pD 2 values of agonists at 6-8 concentrations in duplicate IC 50 values of antagonists at 6-8 concentrations in duplicate pA 2 or pD’ 2 values of antagonists at 3 concentrations, each at least in triplicate Prices upon request. ❚ sample size (including IC 50 follow-up studies) See information page 210. ❚ protocol Agonism/antagonism assessment The agonist activity is evaluated by exposing the tissues to increasing concentrations of the compounds. Where an agonistlike response is obtained, the reference antagonist is tested against the highest test concentration to confirm the involvement of the receptor studied in this response. A reference full agonist is used as a positive control. The antagonist activity is evaluated by testing increasing concentrations of the compounds against a single concentration of the reference agonist. A reference antagonist is used as a positive control. EC 50 /pD 2 values for agonists, IC 50 values for antagonists and maximum responses (Emax) Same protocols as above, with full concentration response curves. pA 2 or pD’ 2 values for antagonists Concentration-response curves to the reference full agonist are obtained in the absence (control) and in the presence of a fixed concentration of the compound. The resulting changes in the agonist curves are used to determine a pA 2 value for competitive antagonism (decrease in the pD 2 value of the agonist) or a pD’ 2 value for non-competitive antagonism (decrease in the maximum response to the agonist). Any of our assay protocols can be customized: Please inquire ❚ deliverables Mean percent of control values, EC 50 /pD 2 , IC 50 , pA 2 or pD’ 2 values. Concentration-response curves. ❚ data turnaround Complete data set is typically available 4 weeks after receipt of the compound at the testing site. Kinases Epigenetic & DNA-related enzymes Other enzymes Specialized cellular assays Standard profiles Testing conditions Ordering information Assay list & index
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in vitro pharmacology 2011 catalog
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Cerep services p. 4 Receptors [GPC
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5 ❚ tool-box for cell-based assay
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7 ❚ profile design Cerep offers a
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9 ❚ data online A powerful web-ba
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11 in vitro pharmacology assays Rec
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13 Cerep services receptors Recept
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15 Adenosine ❚ A 2B - antagonist
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17 alpha 1B - antagonist radioligan
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19 adrenergic ❚ alpha 2C - antago
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adrenergic ❚ 21 beta 3 cellul ar
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-12 -11 -10 -9 -8 -7 -6 -5 -4 -3 bo
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adykinin ❚ 25 B 2 cellul ar Ref.
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27 ❚ cannabinoid CB 1 - agonist r
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29 chemokines ❚ CCR2 cellul ar Re
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31 cholecystokinin ❚ CCK 2 (CCK B
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33 dopamine ❚ D 2S - antagonist r
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dopamine ❚ 35 D 5 cellul ar Ref.
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37 Cerep services ❚ Free fatty ac
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39 galanin ❚ GAL 2 - agonist radi
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41 ❚ Growth hormone-releasing hor
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43 H 3 - agonist radioligand Source
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45 leukotrienes ❚ CysLT 2 (LTC 4
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melanin concentrating hormone ❚
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49 ❚ melatonin Cerep services MT
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51 M 2 - antagonist radioligand bin
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53 muscarinic ❚ M 5 - antagonist
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55 NK 3 - agonist radioligand bindi
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neuropeptide y ❚ 57 Y 1 cellul a
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59 Cerep services ❚ opioid and op
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61 NOP (ORL1) - agonist radioligand
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63 platelet activating factor ❚ P
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65 prostanoid ❚ EP 4 - agonist ra
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67 proteinase-activated ❚ PAR2 ce
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serotonin ❚ 69 5-HT 1A cellul ar
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71 serotonin ❚ 5-HT 2B - agonist
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73 5-HT 7 - agonist radioligand bin
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75 ❚ thyrotropin releasing hormon
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77 ❚ vasopressin Cerep services O
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81 LXRb - agonist radioligand bindi
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85 gaba ❚ GABA A1 (a1, b2, g2) -
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87 glycine (strychnine-insensitive)
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89 ❚ Melatonin MT 3 (ML 2 ) - ago
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91 ❚ Sigma Cerep services sigma (
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93 Cerep services [Voltage-gated ch
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voltage-gated channels [K + channel
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transient receptor potential channe
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99 kainate - agonist radioligand bi
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101 ❚ purinergic channels Cerep s
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103 Cerep services transporters Rec
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105 norepinephrine ❚ norepinephri
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107 Cerep services Kinases Receptor
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109 DDR2 kinase Ref. 2783 Q 3 weeks
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111 protein-tyrosine kinases [Rtk]
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113 FLT-3 kinase Ref. 2866 Q 3 week
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115 KDR kinase (VEGFR2) Ref. 2864 Q
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117 TRKB Ref. 2902 Q 3 weeks Includ
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119 protein-tyrosine kinases [Ctk]
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121 JAK1 Ref. 2619 Q 3 weeks Includ
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123 TXK Ref. 2786 Q 3 weeks Include
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125 CDK6 (cycD3) Ref. 2909 Q 3 week
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protein-SERINE/THREONINE kinases [C
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129 JNK3 Ref. 2916 Q 3 weeks Includ
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131 CaMK1d Ref. 2922 Q 3 weeks Incl
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133 MAPKAPK2 Ref. 3367 Q 3 weeks I
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135 PhKg1 Ref. 2745 Q 3 weeks Inclu
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137 ❚ protein-SERINE/THREONINE ki
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139 MSK1 Ref. 1724 Q 3 weeks Source
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141 PKCe Ref. 2044 Q 3 weeks PKCz R
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143 ROCK2 Ref. 2884 Q 3 weeks Inclu
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145 COT kinase (MAP3K8) Ref. 2003 Q
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147 MKK6/p38a (mutant active) Ref.
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149 ❚ protein-SERINE/THREONINE ki
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151 RAF-1/MEK1 Ref. 1703 Q 3 weeks
Page 153 and 154: 153 other kinases ❚ MYT1 kinase R
Page 155 and 156: 155 other kinases ❚ TBK1 Ref. 33
Page 157 and 158: 157 Cerep services Epigenetic & DNA
Page 159 and 160: 159 HDACs ❚ HDAC3 Ref. 2083 Q 3 w
Page 161 and 162: 161 HDACs ❚ sirtuin 3 Source Subs
Page 163 and 164: 163 Cerep services Other enzymes Re
Page 165 and 166: 165 phosphatases ❚ phosphatase LA
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Page 169 and 170: 169 caspase-3 ❚ Cysteine protease
Page 171 and 172: 171 proteases [aspartic proteases]
Page 173 and 174: 173 proteases [metalloproteases]
Page 175 and 176: phosphodiesterases ❚ 175 PDE4A 1
Page 177 and 178: 177 no synthases ❚ inducible NOS
Page 179 and 180: 179 ❚ Monoamine & neurotransmitte
Page 181 and 182: 181 Cerep services ❚ Transduction
Page 183 and 184: 183 miscellaneous enzymes ❚ carbo
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Page 187 and 188: 187 ion transport systems ❚ Na +
Page 189 and 190: 189 cytokine secretion ❚ IL-2 sec
Page 191 and 192: 191 expression of endothelial adhes
Page 193 and 194: 193 PDGF-stimulated Balb/c 3T3 prol
Page 195 and 196: 195 cerep Standard profiles ExpresS
Page 197 and 198: 197 ❚ Cellular functional GPCR pr
Page 199 and 200: Cerep standard profiles ❚ 199 Dr
Page 201 and 202: Cerep standard profiles ❚ 201 Sa
Page 203: 203 testing conditions Binding, enz
Page 207 and 208: 207 ordering information Quotation
Page 209 and 210: 209 REQUESTED COMPOUND INFORMATION
Page 211 and 212: shipment instructions ❚ 211 For
Page 213 and 214: 213 assay list & index
Page 215 and 216: 215 CDK5/p35 124 CDK6 (cycD3) 125 C
Page 217 and 218: 217 MMP-3 172 MMP-7 172 MMP-8 172 M
Page 219 and 220: contacts ❚ france [Laboratories]
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in vitro PHARMACOLOGY 2011 CATALOG - Cerep

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