The Kinase Chemogenomic Set (KCGS) is a collection of narrow spectrum small molecule kinase inhibitors that has been assembled by the SGC-UNC to study the biology of dark kinases. KCGS is the most diverse and highly annotated publicly-available collection of kinase inhibitors. Version 1.0 of the set contains 188 kinase inhibitors sourced from eight pharma companies and academic laboratories with potent activity on 211 human kinases. Each inhibitor has been cross-screened across hundreds of kinases and only those meeting strict selectivity criteria are included in the set.
The list of kinases covered by the inhibitors in KCGS v1.0 and their distribution across the human kinome:
AAK1 ABL1 ACVR1 ACVR1B ACVRL1 AKT1 AKT2 ALK ATM ATR AURKA AURKB AURKC BLK BMP2K BMPR1A BMPR1B BMPR2 BMX BRAF BRSK1 BRSK2 BTK BUB1 CAMKK1 CAMKK2 CASK CDK1 CDK2 CDK3 CDK4 CDK7 CDK8 CDK9 CDK12 CDK13 CDK19 CDKL2 CDKL5 CHEK1 CHEK2 CIT CLK1 CLK2 CLK3 CLK4 CSF1R CSNK1A1 CSNK1D CSNK1E DAPK3 DCLK3 DDR1 DYRK1A DYRK1B DYRK2 EGFR EIF2AK3 EPHA2 EPHA6 EPHB4 EPHB6 ERBB2 ERBB3 ERBB4 ERN1 FER FES FGFR1 FLT1 FLT3 FLT4 FRK GAK GSG2 GSK3A GSK3B HCK HIPK1 HIPK2 HIPK3 HIPK4 ICK IGF1R IKBKB IKBKE INSR INSRR IRAK1 JAK1 JAK2 JAK3 KDR KIT LATS1 LCK LIMK2 LRRK2 LTK LYN MAP2K1 MAP2K3 MAP2K4 MAP2K5 MAP3K2 MAP3K5 MAP3K7 MAP3K11 MAP3K19 MAP3K20 MAP4K2 MAP4K4 MAPK1 MAPK3 MAPK6 MAPK7 MAPK8 MAPK9 MAPK10 MAPK11 MAPK14 MAPK15 MAPKAPK2 MAPKAPK5 MARK3 MELK MET MINK1 MKNK1 MKNK2 MTOR MUSK MYLK MYLK2 NEK2 NEK3 NEK5 NEK6 NEK9 NLK NTRK1 NTRK2 NTRK3 NUAK1 NUAK2 PAK1 PDGFRA PDGFRB PDPK1 PHKG1 PI4KB PIK3C2B PIK3C2G PIK3C3 PIK3CA PIK3CB PIK3CD PIK3CG PIM1 PIM2 PIM3 PIP4K2C PIP5K1C PKN2 PLK1 PLK2 PLK3 PRKAA2 PRKCD PRKCE PRKCH PRKCQ PRKD1 PRKD2 PRKD3 PRKX PTK2 PTK2B PTK6 RAF1 RET RIOK1 RIOK2 RIPK1 RIPK2 RIPK3 ROCK1 ROCK2 RPS6KA1 RPS6KA2 RPS6KA3 RPS6KA4 RPS6KA5 RPS6KA6 RPS6KB1 SIK1 SRC SRMS STK10 STK16 STK17A STK17B STK36 SYK TAOK3 TBK1 TEK TGFBR1 TNK1 TNK2 TNNI3K TTK TYK2 YES1 ZAP70
For additional information see the KCGS FAQ
The current set is available to any investigator at a non-for-profit organization for an access fee of $3100 that off-sets the resynthesis cost of the small molecule inhibitors. Requestors receive:
A copy of KCGS in 384-well plates as 1 µL of 10 mM DMSO solution
A spreadsheet that lists chemical structure, target kinase, and literature references for each inhibitor
5 x 1 µL of 10 mM DMSO cherry picks upon request
Access to the full kinase selectivity data for each inhibitor
KCGS v1.0 can be requested through the following link.
A list of investigators that have received a copy of KCGS can be found here.
To ensure the continued availability of KCGS, we have embarked on a project to resupply all of the inhibitors in the set. Current status of the resynthesis project is shown below:
Funding to support the assembly and annotation of KCGS was provided by the UNC Eshelman Institute for Innovation, the NIH Illuminating the Druggable Genome (1U24DK116204-01), and the SGC. Kinase inhibitors were made available by AbbVie, Bayer, Boehringer Ingelheim, GlaxoSmithKline, Merck Sharp & Dohme, Pfizer, Takeda, AstraZeneca, and Vertex. Additional kinase inhibitors were provided by Nathanael Gray (Dana Farber Cancer Institute) and Julian Blagg (Cancer Research UK). Screening assays were supported by Promega and Eurofins-DiscoverX. Funding to support resynthesis of KCGS has been provided by the University Cancer Research Fund, UNC Eshelman Institute for Innovation, the Office of the UNC Vice Chancellor for Research, the UNC School of Medicine, and the SGC.