CYP51 Inhibitor

Tebuconazole is an orally active agricultural azole fungicide which can also inhibit CYP51 with IC₅₀s of 0.9 and 1.3 μM for Candida albicans CYP51 (CaCYP51) and truncated Homo sapiens CYP51 (Δ60HsCYP51), respectively. Tebuconazole induces lipid accumulation and oxidative stress in HepG2 Cells. Tebuconazole decreases MAC-T cells viability and proliferation, induces ER-stress-mediated apoptosis and increases oxidative stress levels in MAC-T cells.

Oteseconazole (VT-1161) is a potent and orally active anti-fungal agent. Oteseconazole potently binds to and inhibits Candida albicans cytochrome P45051 (CYP51) activity (K_d ≤39 nM), shows no obvious effect on human CYP51. Oteseconazole also can be used for the research of dermatophytes.

Obtusifoliol is a specific CYP51 inhibitor, Obtusifoliol shows the affinity with K_d values of 1.2 μM and 1.4 μM for Trypanosoma brucei (TB) and human CYP51, respectively.

Opelconazole (PC945), a potent, long-acting antifungal triazole, possesses activity against a broad range of both azole-susceptible and azole-resistant strains of Aspergillus fumigatus. Opelconazole is also a potent, tightly binding inhibitor of A. fumigatus sterol 14α-demethylase activity, CYP51A and CYP51B, with IC₅₀s of 0.23 μM and 0.22 μM, respectively.

CZx-243 is an orally active broad-spectrum antifungal agent. CZx-243 binds to the active site of fungal CYP51 and interferes with ergosterol biosynthesis by depleting ergosterol and causing the accumulation of upstream sterol intermediates. CZx-243 blocks yeast-to-hypha transition; it inhibits the membrane integrity of fungi such as Candida glabrata and Cryptococcus neoformans. CZx-243 significantly reduces renal fungal burden in a systemic mouse model of invasive fungal infection resistant to Fluconazole (HY-B0101). CZx-243 can be used in the research of fungal infections.

Prothioconazole is an orally active broad-spectrum fungicide. Prothioconazole weakly inhibits CaCYP51 activity in Candida albicans, with an apparent IC₅₀ of approximately 120 μM. Prothioconazole disrupts Microtubule stability by reducing the acetylation level of α-tubulin. Prothioconazole induces Mitochondrial dysfunction, oxidative stress, DNA damage, and Apoptosis. Prothioconazole accumulates ¹⁴-methylated sterols and depletes ergosterol in cells, culture media, plants, and animals. Prothioconazole interferes with pyruvate metabolism and glycolysis/gluconeogenesis processes in mouse liver, downregulates Fasn mRNA expression, and induces hepatotoxicity and renal metabolic disorders. Prothioconazole reduces the fertility of female mice. Prothioconazole inhibits body weight gain and increases liver/kidney indices in mice. Prothioconazole can be used in studies related to candidiasis.

Quilseconazole (VT-1129) is an orally active, highly selective fungal cytochrome P450 enzyme Cyp51 inhibitor that can cross the blood-brain barrier. Quilseconazole prevents the synthesis of ergosterol, an important component of the fungal cell membrane, by inhibiting Cyp51. Quilseconazole has minimal effects on human CYP enzymes. Quilseconazole has antifungal activity and can be used in the study of cryptococcal meningitis and other diseases.

Antifungal agent 136 is a CYP51 inhibitor and antifungal agent. Antifungal agent 136 downregulates the expression of interleukin-6 to alleviate inflammatory responses. Antifungal agent 136 exhibits activity against both drug-sensitive and drug-resistant Candida albicans strains. Antifungal agent 136 can be used in the research of fungal infections and inflammatory diseases.

Mefentrifluconazole is a novel azole derivative and used as an agrochemical broad-spectrum antifungal agent. Mefentrifluconazole is a potent, selective and orally active fungal CYP51 (K_d= 0.5 nM) inhibitor, but shows less inhibitory activity on human aromatase (IC₅₀=0.92 μM).

SDZ285428 is a CYP51 inhibitor. SDZ285428 inhibits Trypanosoma cruzi (TC) CYP51 with I/E2 <1 (5 min) and I/E2=9 (1 h). SDZ285428 inhibits Trypanosoma brucei (TB) CYP51 with I/E2 <1 (5 min) and I/E2=35 (1 h).

CYP51/HDAC-IN-1 is a potent, orally active CYP51/HDAC dual inhibitor. CYP51/HDAC-IN-1 inhibits important virulence factors and down-regulated resistance-associated genes. CYP51/HDAC-IN-1 exhibits potent therapeutic effects for both tropical candidiasis and cryptococcal meningitis.

CYP51/PD-L1-IN-4 (compound 14a-2) is a potent dual-target (CYP51/PD-L1) inhibitor, with IC₅₀ values of 0.17 and 0.021 μM, respectively. CYP51/PD-L1-IN-4 exhibits excellent antifungal and antidrug-resistant fungal activity in vitro. CYP51/PD-L1-IN-4 can be used for fungal infections research.

CYP51-IN-5 is a cytochrome P450 14α-demethylase (CYP51) inhibitor and an antifungal (fungal) agent belonging to the triazole derivative class. CYP51-IN-5 is applicable to the research of Candida albicans, Cryptococcus neoformans, Candida parapsilosis, Candida tropicalis, Trichophyton rubrum, Candida krusei and Microsporum gypseum.

CYP51-IN-27 is a sterol 14α-demethylase CYP51 inhibitor with an IC₅₀ of 0.3434 μg/mL. CYP51-IN-27 exhibits antifungal activity and inhibits the production of fungal ergosterol. CYP51-IN-27 can be used for the research of infection, such as rice sheath blight.

CYP51-IN-29 (Compound B3) is a CYP51 inhibitor and antifungal agent. CYP51-IN-29 effectively suppresses the yeast-to-hyphal transition. CYP51-IN-29 exhibits potent antifungal activity against Candida albicans.

CYP51-IN-32 is an antifungal agent with an IC₅₀ of 0.331 μM against CYP51 of Candida albicans. CYP51-IN-32 releases hydrogen sulfide (H₂S) and inhibits hyphal formation and biofilm development of Candida albicans. CYP51-IN-32 can be formulated into PEG-based nanovesicles. CYP51-IN-32 is applicable to the research of Candida albicans infection.

CYP51/Hsp90-IN-1 (Compound MM4) is a dual CYP51/Hsp90 inhibitor. CYP51/Hsp90-IN-1 shows antifungal activity against Candida albicans and effectively inhibits important fungal virulence factors. CYP51/Hsp90-IN-1 is promising for research of invasive candidiasis.

Antifungal agent 137 (Compound 4S) is an antifungal agent. Antifungal agent 137 inhibits Phomopsis sp. (PS), with an EC₅₀ of 0.15 μg/mL. Antifungal agent 137 inhibits lanosterol 14α-demethylase (CYP51), with an IC₅₀ of 5.00 μg/mL. Antifungal agent 137 disrupts the morphology of PS mycelia, impairs cell membrane integrity, and induces an increase in intracellular ROS levels, triggering oxidative stress. Antifungal agent 137 can be used for the study of fungal infection.

CYP51-IN-30 is a CYP51 inhibitor and fungicidal agent. CYP51-IN-30 inhibits CYP51 activity. CYP51-IN-30 displays potent fungicidal activity with an EC₅₀ value of 2.97 mg/L against S. sclerotiorum.