Kinases play an important role in regulating cellular functions and the communication of cells with their environments. When dysregulated, kinases contribute to the development and progression of diseases including cancer and inflammatory and autoimmune diseases. Kinase inhibitors are an important class of therapeutics with over 40 kinase inhibitor drugs approved in the United States. Despite the success of kinase inhibitors as a drug class, the therapeutic potential of individual kinase inhibitors has been limited by the development of drug resistance and by poor potency and selectivity profiles experienced with some agents that can lead to off-target toxicities or diminished efficacy. In addition, currently approved kinase inhibitors target fewer than 10% of the over 500 known human kinases. We believe there is a substantial opportunity to develop novel kinase inhibitor therapies.
Currently approved kinase inhibitors target fewer than 10% of the over 500 known human kinases. We believe there is a substantial opportunity to develop novel kinase inhibitor therapies.
– Mike Taylor
Our Platform
Our proprietary drug discovery Kinase Switch Control platform is based on our deep insight into the biology of kinases. The transformation of a kinase from an inactive to an activated state is dependent upon the interaction of one region of the kinase called the activation switch with an area called the switch pocket; a mechanism of activation that is common among kinases. By directly targeting the switch pocket, we design inhibitors to be broadly active against the target kinase, covering both wild-type and many or all of the known mutant or amplified forms, or spectrum-selective towards several chosen kinases.
While this activation mechanism is common among kinases, the molecular structure of the activation switch and the switch pocket varies among kinases. At Deciphera, we take advantage of this variation to design molecules that inhibit a specific kinase or kinases.
We believe no other kinase inhibitors on the market or active in clinical development directly target the switch pocket region, making Deciphera the only biopharmaceutical company that is currently developing kinase inhibitors using this approach. Our kinase switch control inhibitors interact at a molecular level that is distinct from other kinase inhibitors and are designed to generate higher and more durable rates of response as compared to other kinase inhibitors. Using our kinase switch control inhibitor platform, we have developed a diverse pipeline of differentiated, wholly-owned, orally administered drug candidates that include three clinical-stage and two research-stage programs.
Drug Resistant Kinase Mutations
Within almost all kinases, a molecular control known as the activation switch governs whether the kinase is in the inactive or the active state. Most of the time kinases are in an inactive state and are triggered into the active state when they are needed to direct normal cellular functions. Mutations within kinases, particularly those that involve the activation switch region, can cause uncontrolled kinase signaling within the cell. In addition, kinases may acquire further mutations during treatment with traditional kinase inhibitor drugs that confer resistance to these drugs.
Learn more about our tumor-targeted drug candidate, ripretinib (DCC-2618).
Role of Immunokinases in Cancer
Certain kinases known as immunokinases play a role in the development of cancer through the suppression of the immune system. Tumors suppress immune system cells, such as macrophages and T-cells, essentially shutting off their ability to identify and destroy cancer cells. For instance, tumors may suppress the immune system by sending a signal that activates an immunokinase in immune system cells. The activated kinase then initiates internal signaling within the immune system cells to suppress their function and prevent them from identifying and destroying the cancer cells. Learn more about our immune-targeted drug candidates rebastinib and DCC-3014.
Immune-Targeted Therapies