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 activity against 400 human kinases. Each inhibitor has a Kd <100 nM for its target kinase 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 on our web page. You will complete the on-line Material Transfer and Trust Agreement and submit the processing and distribution fee. Once these are received KCGS will be sent to you in a 384-well plate.

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 fund resynthesis of the individual kinase inhibitors so that it will continue to be available as a public resource.

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 fund resynthesis of the individual kinase inhibitors so that it will continue to be available as a public resource.

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.

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. It is recommended to fill up to 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. As KCGS is currently a limited resource and you require more than the standard dispensement we will work with you to define the minimal volume necessary to enable the proposed experiments and decide if we can meet that need.

Is there space for controls on the KCGS plate?

The first two and last two columns of every plate are left intentionally blank for control wells when plating KCGS.

Which compounds are contained in my plate?

Physical and electronic plate maps are included with every shipment. We will be providing plate maps on our website that people can access using the plate number they receive as well.

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 collecting toxicity data against a range of normal cell lines and will make this data available on our website.

What is the kinome coverage of KCGS?

Using data collected with the DiscoverX KinomeSCAN of 400 human kinases, KCGS covers 52% of the screenable kinome. 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 inhibitor 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 connecting with a data repository such as ChEMBL.

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 must use the set within 90 days. 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 try to supply additional quantities compounds when possible from our internal supplies, but these are often limited. However, we will always provide options for obtaining additional quantities of the compounds through resynthesis.

I have some interesting results. Can I get analogs of compounds of interest?

We have analogs of many of the kinase inhibitors in KCGS that may be useful for establishing structure-activity relationships around a kinase of interest.

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. If you plan to use a KCGS compound in animals, evidence of an appropriate institutional animal care and use committee (IACUC or equivalent) protocol approval is required before we can consider a request of this nature. Quantities of individual compounds maybe severely limited and ultimately preclude supply for an in vivo study.