Please note that we are not in a position to supply cell lines, small molecules or protein reagents to external investigators. However, in the HMS LINCS Database we provide information about the vendors from whom these reagents can be acquired.
The HMS LINCS Center acquires its cell lines and primary cells from a variety of sources. Whenever possible, lines are acquired directly from ATCC or other established cell repositories and master stocks prepared after a minimum number of passages. Cell line identity also is validated by STR profiling. Complete information about all cells and cell lines used at HMS LINCS can be found in the HMS LINCS Database. Additional cell types are regularly added to our collection as a result of collaboration with outside laboratories.
Example cell types studied at HMS LINCS:
Breast cancer cells in the ICBP43 panel
The ICBP43 panel of 43 breast cancer cell lines represents a diverse set of tumor types (Her2+, triple negative, Basal A/B, etc.) assembled by investigators, the lab of Joe Gray at Oregon Health Sciences University in particular, working with the National Cancer Institute’s Integrative Cancer Biology Program (ICBP). Identical isolates of these cell lines have been distributed to multiple laboratories in the US, and the cells have been profiled extensively at the genomic level.
Primary synovial fibroblasts
Commercially-available primary synovial fibroblasts from multiple normal donors and donors suffering from rheumatoid arthritis are being profiled to identify therapeutically-relevant signaling networks and small molecule inhibitors.
Commercially-available iPS-derived cardiomyocytes are being profiled to understand kinase inhibitor-induced cardiotoxicity.
July 2, 2015: The HMS LINCS cell collection was updated to include only cells used at Harvard Medical School and in collaboration with other LINCS Phase II investigators. An archive of all cell information posted in the HMS LINCS database before July 2, 2015, is available here and also at LIFE.
The HMS LINCS Center currently focuses mostly on two types of perturbagens: small molecule protein kinase inhibitors and naturally occurring growth factors, cytokines and chemokines. Small molecules targeting chromatin structures are beginning to be studied. Complete information about all perturbagens used at HMS LINCS can be found in the HMS LINCS Database.
Small molecule kinase inhibitors
Many kinase inhibitors used in the HMS LINCS Center are in clinical use, particularly as anti-cancer drugs, and many more are in development. Discoveries made by the HMS LINCS Center should therefore have good translational potential. In addition, we expect to monitor the effects of kinase inhibitors in the presence of standard-of-care therapeutics that do not target kinases (e.g. paclitaxel).
As of the middle of 2015, we have obtained or synthesized >375 small molecule kinase inhibitors, some commercial and some unique to our LINCS Center. The HMS LINCS inhibitor collection will continue to be expanded in the next few years. Basic information about each inhibitor (including SMILES, InChi, and rendered structures; compound names and synonyms; vendor/supplier name and batch information; quality control information such as NMR and LCMS data; and target information and relevant references) are reported in the HMS LINCS Database. Please note that we are not in a position to provide these reagents to outside investigators other than LINCS collaborators.
Kinase specificity profiles
We have profiled the biochemical specificity of many of the kinase inhibitors across 442 purified recombinant kinases using the KINOMEscan method (outsourced to DiscoveRx). KiNativ in situ kinase profiles for several of the inhibitors have been collected as well. We anticipate that these KINOMEscan and KiNativ specificity data will be of high value to the community and will help us to quantify polypharmacology effects of these perturbagens on signaling networks. Finally, more than 200 compounds from the HMS LINCS inhibitor collection also have been provided to the Broad Institute LINCS Center for profiling in their L1000 assay.