Inxight Drugs

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Status:

Possibly Marketed Outside US

First approved in 2012

Class (Stereo):

CHEMICAL (ACHIRAL)

Carbon monoxide (CO) is a colorless, odorless, tasteless, and nonirritating but highly toxic gas generated by both natural and manufactured processes. CO displays many physiological roles in the neuronal, cardiovascular, and immune systems, as well a...

s in the respiratory, reproductive, gastrointestinal, and urogenital apparatus, including anti‐apoptotic, anti‐inflammatory, anti‐oxidant, anti‐proliferative, and vasodilator effects. Although many pathologies, including cancer, hematological diseases, hypertension, heart failure, inflammation, sepsis, neurodegeneration, and sleep disorders, have been linked to abnormal endogenous CO metabolism and functions, CO displays therapeutic actions. CO has demonstrated therapeutic potential against a wide range of human diseases. However, development of CO as a therapeutic agent is severely impeded, primarily due to the lack of pharmaceutically acceptable delivery forms of CO. The therapeutic use of CO is based on (i) the induction or gene transfer of HO‐1, (ii) the inhalation of gaseous CO, and (iii) the use of CO‐releasing molecules (CO‐RMs). There is a large amount of broad preclinical evidence of the benefits of CO in large and small animal models. Importantly, CO is effective both as a prophylactic and as a therapeutic in diverse models, such as malaria, organ transplantation and pulmonary hypertension. Inhaled CO and CO-RMs are in development as therapeutics; inhaled CO is being tested in Phase II clinical trials for kidney transplantation and various CO-RMs are under preclinical evaluation. The precise molecular targets for CO remain unclear with a wide range of evidence for both haem and non-haem targets. A commonality revolves around the contributions of the mitochondria and alterations in cellular bioenergetics. Inhaled CO delivery can be accomplished with an innovative delivery device. In addition strong medicinal chemistry is driving CO-RM development with efforts towards tissue specificity and the appropriate pharmacokinetic and pharmacodynamic profiling. Inhaled CO has found wide applications in basic research in examining CO’s physiological and pathological roles, yet its application in human has many limitations, such as difficulty in precise dose control, lack of portability and inability for targeted delivery, among others. In order to mitigate these limitations, a family of transition metal based CO-releasing molecules (CO-RMs) have been elegantly devised, and have shown CO-associated biological outcomes both in vitro and in vivo. Proterris is developing an inhaled carbon monoxide (CO) therapy for the treatment of idiopathic pulmonary fibrosis (IPF), delayed graft function (DGF), acute kidney injury and renal fibrosis.

Development Status

Approval Year

Substance Class

Code System

Substance Form

CARBON MONOXIDE

7U1EE4V452