BRISBANE, Calif., April 18, 2023 (GLOBE NEWSWIRE) -- Nitrase Therapeutics, Inc., a biopharmaceutical company deploying its NITROME platform to build a pipeline of therapies targeting nitrases, a new class of enzymes discovered in-house that are involved in a broad variety of diseases, today announced the company presented preclinical data highlighting nitrases as newly-discovered therapeutic targets for oncology in a poster presentation (abstract #3941) at the 2023 American Association for Cancer Research (AACR) Annual Meeting. The data demonstrated that several proteins known to regulate tumor cell survival and/or evasion of immune surveillance, such as PAK4, BAX and RhoA, are specifically nitrated by different nitrases and this alters their biochemical activities. High expression of certain nitrases is associated with poor prognosis as determined by the Human Protein Atlas, and several of them are associated with liver or kidney cancers.
“We have once again established the critical role of nitrases in disease biology; this time, with the discovery that the nitration of known cancer-associated proteins alters their activity and is likely a driver of tumorigenesis,” said Irene Griswold-Prenner, Ph.D., chief scientific officer of Nitrase Therapeutic. “Therefore, targeted inhibition or degradation of the specific nitrase, or of the nitrated protein itself, could be a promising therapeutic approach in cancer. We are developing modulators of these nitrases as potential drug candidates for several underserved cancers.”
Company-identified nitrases were evaluated for specific cancer associations. It was discovered that PAK4, a protein that has been implicated as an oncogenic driver, as well as in immune evasion, is specifically nitrated by Nitrase #3 causing increased kinase activity. Similarly, RhoA, a protein implicated in the oncogenic state of tumors is nitrated by Nitrase #12. This nitration activates RhoA biochemically and in cells. BAX is a specific substrate for Nitrase #11, and its cytochrome C release from the mitochondria is reduced upon nitration.
Additionally, in silico analysis of nitrases for overall survival association was performed. Utilizing The Cancer Genome Atlas (TCGA) RNA expression data and The Human Protein Atlas, nitrases were screened for association with overall survival in relation to nitrase RNA expression. Nitrases showing lower overall survival with high nitrase RNA expression and a p. value of <0.001 were identified as negatively prognostic. Nine nitrases showed negative prognostic association, suggesting that they could be favorable therapeutic targets. Additionally, several nitrases were negatively prognostic for kidney cancer or liver cancer.
About
Nitrase Therapeutics, Inc.
Nitrase Therapeutics is a pioneering biopharmaceutical company deploying its
unique NITROME platform to unlock the therapeutic potential of nitrases, a new
class of enzymes that it discovered, to develop a pipeline of therapies against
a broad range of diseases. The medicines that Nitrase Therapeutics is
developing will target these enzymes and potentially help slow or halt the progression
of numerous diseases in which nitrases and nitro-substrates play a role,
including Parkinson’s, cancer, immunological and fibrotic diseases. Nitrase
Therapeutics (under the former name Nitrome Biosciences) has been widely
recognized and has won multiple awards including the prestigious Target
Advancement grant from The Michael J. Fox Foundation for Parkinson's Research
(MJFF). Nitrase Therapeutics is located in Brisbane, CA, and its investors
include Sofinnova Partners, AbbVie Ventures, Dementia Discovery Fund, Bristol
Myers Squibb, Mission Bay Capital and Alexandria Venture Investments. For more
information, please visit the company’s website at www.nitrasetx.com.
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