Why are you charging for KCGS?
KCGS is currently a finite resource that is available in limited supply through donation of kinase inhibitors from pharma companies and academic labs. We will use all funds raised through distribution of KCGS to finance resynthesis of the kinase inhibitors so we can continue to make it available as a public resource.
What is KCGS?
The Kinase Chemogenomic Set (KCGS) v1.0 is a collection of 188 well-annotated small molecule ATP-competitive inhibitors that were produced in drug discovery programs targeting protein kinases. Each inhibitor has been profiled for binding against 400 human kinases at DiscoverX. Each inhibitor has a Kd < 100 nM for its target kinases with a selectivity index S10 < 0.04 at 1 µM. In total, KCGS indexes 212 human kinases including many poorly studied (dark) kinases. KCGS is available from the SGC in aliquots of 1 µL of a 10 mM solution in DMSO.
How do I obtain KCGS?
Detailed instructions for requesting the set are posted here.
Requesting the set is a 3 step process:
Step 1: Fill out the KCGS web form
Step 2: Download the MTA file (that will appear after the web form is completed) and have it signed by an authorized institutional signator.
Step 3: Log into infoporte to upload the signed MTA and pay for your order by credit card. Once the MTA has been approved, a payment link will be emailed to you. After payment has been received, your compounds will be shipped to the address provided. Please refer any questions to firstname.lastname@example.org.
How did you decide the $3100 processing and distribution fee?
A survey of recipients of PKIS and PKIS2 indicated that the majority would have paid between $1000-$5000 for access to the sets. All funds raised through distribution of KCGS will be used to support resynthesis of the kinase inhibitors so we can provide the set for years to come.
What if I cannot afford the processing and distribution fee?
We will gladly work with you to submit grant applications to raise the funds. It is likely that the KCGS processing and distribution fee will be only a fraction of the operational cost of your proposed experiment.
Why do I have to sign an MTA?
Many of the kinase inhibitors in KCGS have been made available through a license that requires UNC to document the transfer of the material to a third party. The MTA was developed to support the principles of open science and has been used successfully with over 300 laboratories. The MTA allows you unrestricted use of the compounds in cells, but in return you must agree to publish your data and to not restrict the ability of other scientists to use the compounds in their experiments.
Can I request changes to the wording of the MTA?
No. We cannot customize it to individual institutions.
Who should sign the MTA?
Any individual with institutional signing authority.
How should we store KCGS upon receipt?
We recommend storing the plate between -20 and -80°C until use. Researchers are advised to avoid multiple freeze-thaw cycles with the KCGS plate to ensure best results.
What concentration range should be used when running a cellular screen using the KCGS library?
KCGS contains potent kinase inhibitors that have been profiled for selectivity at 1 μM. We recommend cellular screens be conducted no higher than 1 μM. If assay throughput can accommodate it, another option is to conduct the initial screening at 2-3 different concentrations; for example 10 nM, 100 nM, and 1 μM.
How are KCGS compounds solubilized?
All KCGS compounds are dissolved in DMSO and dispensed as 1 μL of a 10 mM stock solution.
What kind of plate is KCGS dispensed into?
KCGS is dispensed in a Greiner #781280 V-bottom polypropylene 384-well plate as 1 μL of a 10 mM stock solution.
What is the total capacity of the wells in the KCGS plate?
The capacity of the KCGS wells is 130 μL. We recommend volumes at or below 100 μL if automation is involved.
Is there a recommended dilution protocol for the KCGS plate?
When ready to dilute the plates, we recommend bringing the KCGS plate to room temperature, spinning down all liquid, diluting and agitating. We recommend diluting with DMSO. For example, adding 9 μL of DMSO to the 1 μL of 10 mM stock will yield 10 μL of 1 mM stock in your KCGS plate. A 1000-fold dilution of the stock plate in assay media will yield 10 mL of a 1 μM solution containing 0.1% DMSO.
How much can I request?
We dispense KCGS as 1 µL of a 10 mM solution in DMSO. KCGS is currently a limited resource. If you require more than the standard dispensement we will work with you to define the minimum volume necessary to enable the proposed experiments and then decide if we can meet that need.
Is there space for controls on the KCGS plate?
Since KCGS is only 188 compounds there are plenty of available wells for suitable controls.
Which compounds are contained in my plate?
A physical copy of the plate layout is included with every shipment. For an electronic copy of the plate layout click here to access.
What is known about the stability of compounds in KCGS?
The compounds in KCGS are not known to have any light or air sensitivities. A QC plate was analyzed prior to dispensing the KCGS plates. However, researchers are advised to avoid multiple freeze-thaw cycles with the KCGS plate to ensure best results.
Does SGC-UNC have general toxicity data for the KCGS Library?
We are putting a plan in place to obtain this data. We will make the results available on our website when testing is complete.
What is the kinome coverage of KCGS?
Using data collected with the DiscoverX KINOMEscan platform that screens for 400 human kinases, KCGS covers 212 kinases. Each inhibitor has a Kd < 100 nM for its target kinase with a selectivity index S10 < 0.04 at 1 µM. There are no highly promiscuous kinase inhibitors in KCGS.
Where is the KCGS data?
The chemical structures of the inhibitors and the kinase activity data are available on our website randomactsofkinases.org
How do I share data generated with KCGS?
The data can be published in scientific literature, shared by emailing it to us, or by uploading the data to an open access site such as ChEMBL or PubChem.
Do I need to include SGC-UNC scientists on any publications that arise from use of the KCGS?
We do not feel that simple supply of compounds justifies inclusion as coauthors. If we add something more to a collaborative effort, please use normal academic standards for coauthorship. However, all publications should identify the source of KCGS as the SGC-UNC and you should send a copy of the citation to us upon publication. We will post a list of all publications arising from the use of KCGS on our website.
What do I need to put in the Acknowledgments section of a publication?
We recommend using the following text “KGCS was supplied by the SGC-UNC and contains kinase inhibitors that were made available by GlaxoSmithKline, Takeda, Pfizer, Boehringer Ingelheim, Vertex, Harvard University, Cancer Research UK, and the SGC.”
What are the requirements for using KCGS?
Recipients of KCGS will be identified on our website. You must communicate results to us and make all data derived from use of the sets publically available within a reasonable amount of time.
I have some interesting results. Can I get additional quantities of compounds of interest?
We will supply additional quantities of 5 inhibitors at 5 µL each for follow-up. For larger quantities we can provide more material priced by amount required.
I have some interesting results. Can I get analogs of compounds of interest?
The SGC-UNC has analogs of many of the kinase inhibitors in KCGS that may be useful for establishing structure-activity relationships around a kinase of interest. Please contact us if you are interested in collaborating.
I want to pursue an in vivo experiment with a molecule from KCGS. Is this possible?
KCGS is formatted for screening in cells and little is known about the pharmacokinetic properties of the individual inhibitors. Currently we do not have quantities sufficient to provide for in vivo studies. We are happy to provide details needed for outsourcing the scale-up of individual compounds.