2,3-Disubstituted pyrido[3,4-b]pyrazine-containing Compounds as Kinase Inhibitors

Purdue University researchers have synthesized kinase inhibitors that display potent anti-proliferative effects when dosed into lung, pancreatic, and colon cancer cells. Overactive kinases are a primary driver of cancer cell proliferation. Accordingly, many chemotherapeutic regimens contain kinase inhibitors; however, current kinase targeting compounds are not effective in treating aggressive forms of lung, pancreatic, and colon cancers. Purdue University researchers have optimized previously identified kinase inhibitors to achieve a higher potency against many lung, pancreatic, and colon cancer cell lines. These compounds were tested against the NCI-60 cancer cell panel and have low sub micromolar GI50 values. For example, the GI50 against some colon cancers are as low as 5 nM. These compounds also have IC50 values of 25 nM against proliferation of the MiaPaCa-2 pancreatic cancer cell line. The potency of the compounds toward multiple aggressive cancer cell lines makes them promising cancer therapeutic candidates for future development.

Technology Validation: The compounds were tested against the NCI-60 cancer cell line panel and exhibit nanomolar GI50 values in some cell lines.

Advantages

-Inhibits Growth of Multiple Cancer Cell Lines

-Increased Potency versus Previously Identified Molecules

Applications

-Cancer Therapies

-Cancer Relapse

-Kinase Inhibitors

Related publications:

Targeting RET Solvent-Front Mutants with Alkynyl Nicotinamide-Based Inhibitors

https://doi.org/10.1158/1535-7163.MCT-22-0629

TRL: 3

Intellectual Property:

Keywords: kinase inhibitors, anti-proliferative, lung cancer, pancreatic cancer, colon cancer, cancer cell proliferation, chemotherapeutic regimens, NCI-60 cancer cell panel, GI50, IC50, cancer therapeutic candidates