Browsing Pathways
Showing 124391 -
124400 of 605359 pathways
SMPDB ID | Pathway Name and Description | Pathway Class | Chemical Compounds | Proteins |
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SMP0002699View Pathway |
IRT1 |
Signaling
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SMP0127942View Pathway |
IRX-2 Drug Metabolism |
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SMP0130443View Pathway |
Isaralgagene civaparvovec Drug Metabolism |
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SMP0129586View Pathway |
Isatuximab Drug Metabolism |
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SMP0125814View Pathway |
Isavuconazole Action PathwayIsavuconazole is an triazole antifungal. It works by inhibiting fungal cell membrane synthesis. Invasive fungal infections pose significant clinical challenges for patients, especially those who are immunocompromised. In vitro, most of the Candida species, most Aspergillus species, Mucorales, Cryptococcus spp., Fusarium species, dermatophytes and dimorphic fungi displayed susceptibility to isavuconzaole. Resistance to isavuconazole has been associated with the mutation in the target gene CYP51. Isavucoanzole exhibits antifungal activity against most strains of Aspergillus flavus, Aspergillus fumigatus, Aspergillus niger, and Mucorales such as Rhizopus oryzae and Mucormycetes species in vivo and in vitro.
Isavuconazole disrupts the biosynthesis of ergosterol, which is a key component of fungal cell membrane. It inhibits cytochrome P-450 dependent enzyme lanosterol 14-alpha-demethylase that mediates the conversion of lanosterol to ergosterol. The side arm of of the active isavuconazole molecule allows for greater affinity for the binding pocket in the fungal CYP51 protein by orienting the triazole ring of the molecule to engage with the heme moiety at the bottom of the binding pocket. This explains the wide antifungal spectrum of isavuconazole and possible cross-resistance to other triazoles. As a result of lanosterol 14-alpha-demethylase inhibition, toxic methylated sterol precursors such as 14-α-methylated lanosterol, 4,14-dimethylzymosterol, and 24-methylenedihydrolanosterol alter the function of fungal membrane and accumulate within the fungal cytoplasm. Depletion of ergosterol within the fungal cell membrane leads to decreased structural integrity and function of the cell membrane, inhibited fungal cell growth and replication, and ultimately cell death. Mammalian cell demethylation is less sensitive to isavuconazole inhibition.
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Drug Action
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SMP0144742View Pathway |
Isavuconazole Drug Metabolism Action Pathway |
Drug Action
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SMP0125818View Pathway |
Isavuconazonium Action PathwayIsavuconazonium is a second-generation triazole antifungal which is used to treat invasive aspergillosis and invasive mucormycosis. Due to low solubility in water of isavuconazole on its own, the isovuconazonium formulation is favorable as it has high solubility in water and allows for intravenous administration. This formulation also avoids the use of a cyclodextrin vehicle for solubilization required for intravenous administration of other antifungals such as voriconazole and posaconazole, eliminating concerns of nephrotoxicity associated with cyclodextrin.
Isavuconazonium disrupts the biosynthesis of ergosterol, which is a key component of fungal cell membrane. It inhibits cytochrome P-450 dependent enzyme lanosterol 14-alpha-demethylase (sterol 14-α-demethylase) that mediates the conversion of lanosterol to ergosterol. As a result of lanosterol 14-alpha-demethylase inhibition, toxic methylated sterol precursors such as 14-α-methylated lanosterol, 4,14-dimethylzymosterol, and 24-methylenedihydrolanosterol alter the function of fungal membrane and accumulate within the fungal cytoplasm. Depletion of ergosterol within the fungal cell membrane leads to decreased structural integrity and function of the cell membrane, inhibited fungal cell growth and replication, and ultimately cell death.
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Drug Action
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SMP0144060View Pathway |
Isavuconazonium Drug Metabolism Action Pathway |
Drug Action
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SMP0129735View Pathway |
Iscalimab Drug Metabolism |
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SMP0002265View Pathway |
ischemia reperfusion |
Physiological
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Showing 124391 -
124400 of 132183 pathways