| Identification | Back Directory | [Name]
HSP90-IN-9 | [CAS]
2765247-36-5 | [Synonyms]
HSP90-IN-9
3-?Isoxazolecarboxamide?, 5-?(4,?6-?dihydroxy-?4'-?methyl[1,?1'-?biphenyl]?-?3-?yl)?-?N-?ethyl-?4-?[4-?(4-?morpholinylmethyl)?phenyl]?- |
| Hazard Information | Back Directory | [Uses]
HSP90-IN-9 is a potent and selective HSP90 inhibitor. HSP90-IN-9 displays a fungicidal effect in a dose-dependent manner. HSP90-IN-9 inhibits fungal biofilm formation and fungal morphological changes after being combined with FLC. HSP90-IN-9 recovers FLC resistance by down-regulating the expression of related genes (ERG11, CDR1 and CDR2)[1]. | [in vivo]
HSP90-IN-9 (10 mg/kg; i.v.) exhibits moderate pharmacokinetic properties in SD rats[1].
HSP90-IN-9 (A17 (10 mg/kg)+FLC (1 mg/kg); i.p.; once a day for 5 days) exhibits potent in vivo antifungal efficacy by reducing the colonization and dissemination of fungi in tissue[1].
Pharmacokinetic Parameters of HSP90-IN-9 in male Sprague-Dawley (SD) rats[1].
| dose (mg/kg) | T1/2 (h) | C0 (ng/mL) | AUC(0-t) (h*ng/mL) | AUC(0-∞) (h*ng/mL) | Vz (L/kg) | Cl (mL/min/kg) | MRT(0-∞) (h) | | 10 mg/kg | 1.26±0.31 | 4752.50±44.54 | 3005.15±35.59 | 3028.95±54.14 | 11.25±3.69 | 101.77±1.96 | 1.12±0.07 |
male Sprague-Dawley (SD) rats; 10 mg/kg; i.v. [1]| Animal Model: | male Sprague-Dawley (SD) rats[1] | | Dosage: | 10 mg/kg | | Administration: | i.v. | | Result: | Exhibited moderate pharmacokinetic properties in SD rats. |
| Animal Model: | female SD rats, 160-180 g (IFI rat model)[1] | | Dosage: | 10 mg/kg, A17 (10 mg/kg)+FLC (1 mg/kg) | | Administration: | i.p., once a day, 5 days | | Result: | Exhibited potent in vivo antifungal efficacy by reducing the colonization and dissemination of fungi in tissue. |
| [IC 50]
HSP90 | [References]
[1] Yin W, et al. Species-Selective Targeting of Fungal Hsp90: Design, Synthesis, and Evaluation of Novel 4,5-Diarylisoxazole Derivatives for the Combination Treatment of Azole-Resistant Candidiasis. J Med Chem. 2022, 65(7):5539-5564. DOI:10.1021/acs.jmedchem.1c01991 |
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