Sonlicromanol

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'''Sonlicromanol (KH176)''' is a clinical-stage oral drug compound developed by Khondrion as a potential treatment for primary and secondary mitochondrial diseases, such as [[Leigh syndrome|Leigh's Disease]], [[MELAS syndrome|MELAS]] and [[LHON]].Khondrion. (2016, September 7). ''KH176 Phase 2 clinical trial''. Khondrion. https://www.khondrion.com/kh176-phase-2-clinical-trial/ Due to dysfunctional mitochondria, an increased level of cellular [[reactive oxygen species]] (ROS) is observed in these patients, causing a wide range of symptoms. The active metabolite of Sonlicromanol (KH176m, or KH183) has several mechanisms of action, acting both as antioxidant and as reactive oxygen species (ROS)-redox modulator.{{Cite journal |last1=Beyrath |first1=Julien |last2=Pellegrini |first2=Mina |last3=Renkema |first3=Herma |last4=Houben |first4=Lisanne |last5=Pecheritsyna |first5=Svetlana |last6=van Zandvoort |first6=Peter |last7=van den Broek |first7=Petra |last8=Bekel |first8=Akkiz |last9=Eftekhari |first9=Pierre |last10=Smeitink |first10=Jan A. M. |date=2018-04-26 |title=KH176 Safeguards Mitochondrial Diseased Cells from Redox Stress-Induced Cell Death by Interacting with the Thioredoxin System/Peroxiredoxin Enzyme Machinery |journal=Scientific Reports |language=en |volume=8 |issue=1 |page=6577 |doi=10.1038/s41598-018-24900-3 |issn=2045-2322 |pmc=5920042 |pmid=29700325|bibcode=2018NatSR...8.6577B }} Through selective suppression of [[MPGES-1|microsomal prostaglandin E synthase-1 (mPGES-1)]], Sonlicromanol even has potency as anti-cancer drug for mPGES-1 overexpressing cancer like [[prostate cancer]].{{Cite journal |last1=Jiang |first1=Xiaolan |last2=Renkema |first2=Herma |last3=Smeitink |first3=Jan |last4=Beyrath |first4=Julien |date=2021-07-09 |title=Sonlicromanol's active metabolite KH176m normalizes prostate cancer stem cell mPGES-1 overexpression and inhibits cancer spheroid growth |journal=PLOS ONE |language=en |volume=16 |issue=7 |article-number=e0254315 |doi=10.1371/journal.pone.0254315 |issn=1932-6203 |pmc=8270194 |pmid=34242345|bibcode=2021PLoSO..1654315J |doi-access=free }} Sonlicromanol has been evaluated in phase II clinical trials in the KHENERGYZE,{{Cite journal |date=2019 |title=The KHENERGYZE study |journal=Case Medical Research }} KHENEREXT{{Cite journal |last=Khondrion BV |date=2021-10-15 |others=Julius Clinical, The Netherlands, ProPharma Group, Certara |title=A Phase IIb Open-label, Multi-centre, Extension Study to Explore the Long-term Safety and Efficacy of KH176 in Subjects With a Genetically Confirmed Mitochondrial DNA tRNALeu(UUR) m.3243A>G Mutation Who Have Completed the KHENERGYZE Study KH176-202. |url=https://clinicaltrials.gov/ct2/show/NCT04604548}} and KHENERGYC{{Cite journal |last=Khondrion BV |date=2022-01-26 |others=Julius Clinical, The Netherlands, ProPharma Group, Europees Fonds voor Regionale Ontwikkeling (EFRO), Ardena, Certara |title=A Randomized Placebo Controlled, Double-blind Phase II Study to Explore the Safety, Efficacy and Pharmacokinetics of Sonlicromanol in Children With Genetically Confirmed Mitochondrial Disease |url=https://clinicaltrials.gov/ct2/show/study/NCT04846036}} studies as potent candidate in treatment for mitochondrial diseases and results have been [[doi:10.1093/brain/awae277|published]]. Specifically, sonlicromanol showed meaningful improvements on key symptoms associated with mitochondrial diseases. [https://clinicaltrials.gov/study/NCT06451757?term=KHENERFIN&rank=1 A phase 3 trial] in patients with the m.3243A>G variant has been announced and is expected to start recruitment in 2025. Also, a [[Long COVID]] proof-of-concept trial is expected to start recruitment in [https://www.khondrion.com/news/khondrion-and-amsterdam-umc-announce-to-initiate-phase-2-clinical-trial-of-sonlicromanol-to-combat-long-term-post-covid-symptoms 2025].

'''Sonlicromanol (KH176)''' is a clinical-stage oral drug compound developed by Khondrion as a potential treatment for primary and secondary mitochondrial diseases, such as [[Leigh syndrome|Leigh's Disease]], [[MELAS syndrome|MELAS]] and [[LHON]].Khondrion. (2016, September 7). ''KH176 Phase 2 clinical trial''. Khondrion. https://www.khondrion.com/kh176-phase-2-clinical-trial/ Due to dysfunctional mitochondria, an increased level of cellular [[reactive oxygen species]] (ROS) is observed in these patients, causing a wide range of symptoms. The active metabolite of Sonlicromanol (KH176m, or KH183) has several mechanisms of action, acting both as antioxidant and as reactive oxygen species (ROS)-redox modulator.{{Cite journal |last1=Beyrath |first1=Julien |last2=Pellegrini |first2=Mina |last3=Renkema |first3=Herma |last4=Houben |first4=Lisanne |last5=Pecheritsyna |first5=Svetlana |last6=van Zandvoort |first6=Peter |last7=van den Broek |first7=Petra |last8=Bekel |first8=Akkiz |last9=Eftekhari |first9=Pierre |last10=Smeitink |first10=Jan A. M. |date=2018-04-26 |title=KH176 Safeguards Mitochondrial Diseased Cells from Redox Stress-Induced Cell Death by Interacting with the Thioredoxin System/Peroxiredoxin Enzyme Machinery |journal=Scientific Reports |language=en |volume=8 |issue=1 |page=6577 |doi=10.1038/s41598-018-24900-3 |issn=2045-2322 |pmc=5920042 |pmid=29700325|bibcode=2018NatSR...8.6577B }} Through selective suppression of [[MPGES-1|microsomal prostaglandin E synthase-1 (mPGES-1)]], Sonlicromanol even has potency as anti-cancer drug for mPGES-1 overexpressing cancer like [[prostate cancer]].{{Cite journal |last1=Jiang |first1=Xiaolan |last2=Renkema |first2=Herma |last3=Smeitink |first3=Jan |last4=Beyrath |first4=Julien |date=2021-07-09 |title=Sonlicromanol's active metabolite KH176m normalizes prostate cancer stem cell mPGES-1 overexpression and inhibits cancer spheroid growth |journal=PLOS ONE |language=en |volume=16 |issue=7 |article-number=e0254315 |doi=10.1371/journal.pone.0254315 |issn=1932-6203 |pmc=8270194 |pmid=34242345|bibcode=2021PLoSO..1654315J |doi-access=free }} Sonlicromanol has been evaluated in phase II clinical trials in the KHENERGYZE,{{Cite journal |date=2019 |title=The KHENERGYZE study |journal=Case Medical Research }} KHENEREXT{{Cite journal |last=Khondrion BV |date=2021-10-15 |others=Julius Clinical, The Netherlands, ProPharma Group, Certara |title=A Phase IIb Open-label, Multi-centre, Extension Study to Explore the Long-term Safety and Efficacy of KH176 in Subjects With a Genetically Confirmed Mitochondrial DNA tRNALeu(UUR) m.3243A>G Mutation Who Have Completed the KHENERGYZE Study KH176-202. |url=https://clinicaltrials.gov/ct2/show/NCT04604548}} and KHENERGYC{{Cite journal |last=Khondrion BV |date=2022-01-26 |others=Julius Clinical, The Netherlands, ProPharma Group, Europees Fonds voor Regionale Ontwikkeling (EFRO), Ardena, Certara |title=A Randomized Placebo Controlled, Double-blind Phase II Study to Explore the Safety, Efficacy and Pharmacokinetics of Sonlicromanol in Children With Genetically Confirmed Mitochondrial Disease |url=https://clinicaltrials.gov/ct2/show/study/NCT04846036}} studies as potent candidate in treatment for mitochondrial diseases and results have been [[doi:10.1093/brain/awae277|published]]. Specifically, sonlicromanol showed meaningful improvements on key symptoms associated with mitochondrial diseases. [https://clinicaltrials.gov/study/NCT06451757?term=KHENERFIN&rank=1 A phase 3 trial] in patients with the m.3243A>G variant has started recruitment. Also, a [[Long COVID]] proof-of-concept trial [https://clinicaltrials.gov/study/NCT07298005 has started recruitment].

[[File:Sonlicromanol and metabolite.png|thumb|The chemical structures of Sonlicromanol - KH176 and its metabolite KH183 - KH176m]]

[[File:Sonlicromanol and metabolite.png|thumb|The chemical structures of Sonlicromanol - KH176 and its metabolite KH183 - KH176m]]