Oteseconazole
(Synonyms: VT-1161) 目录号 : GC36822
Oteseconazole (VT-1161) 是一种有效、可口服的抗真菌剂，有效结合并抑制白色念球菌的 CYP51 (Kd，<39 nM)，但对人 CYP51 无明显作用。
Cas No.:1340593-59-0
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Oteseconazole (VT-1161) is an orally active anti-fungal agent, potently binds to and inhibits Candida albicans CYP51 (Kd, <39 nM), shows no obvious effect on human CYP51[1][2].
[1]. Warrilow AG, et al. The clinical candidate VT-1161 is a highly potent inhibitor of Candida albicans CYP51 but fails to bind the human enzyme. Antimicrob Agents Chemother. 2014 Dec;58(12):7121-7. [2]. Garvey EP, et al. VT-1161 dosed once daily or once weekly exhibits potent efficacy in treatment of dermatophytosis in a guinea pig model. Antimicrob Agents Chemother. 2015 Apr;59(4):1992-7.
| Cas No. | 1340593-59-0 | SDF | |
| 别名 | VT-1161 | ||
| Canonical SMILES | O[C@@](CN1C=NN=N1)(C(C=CC(F)=C2)=C2F)C(F)(C3=CC=C(C4=CC=C(OCC(F)(F)F)C=C4)C=N3)F | ||
| 分子式 | C23H16F7N5O2 | 分子量 | 527.39 |
| 溶解度 | DMSO: ≥ 270 mg/mL (511.96 mM) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.8961 mL | 9.4806 mL | 18.9613 mL |
| 5 mM | 0.3792 mL | 1.8961 mL | 3.7923 mL |
| 10 mM | 0.1896 mL | 0.9481 mL | 1.8961 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Oteseconazole: First Approval
Drugs 2022 Jun;82(9):1017-1023.PMID:35713845DOI:10.1007/s40265-022-01734-y.
Oteseconazole (VIVJOA™) is an orally administered azole antifungal agent developed by Mycovia Pharmaceuticals for the treatment of fungal infections. It inhibits cytochrome P450 (CYP) 51, thereby affecting the formation and integrity of the fungal cell membrane, but has a low affinity for human CYP enzymes due to its tetrazole metal-binding group. Oteseconazole is the first agent to be approved (in April 2022) for recurrent vulvovaginal candidiasis (RVVC) in the USA, where it is indicated to reduce the incidence of RVVC in females with a history of RVVC who are NOT of reproductive potential. Clinical development for the treatment of onychomycosis, and invasive and opportunistic infections is ongoing. This article summarizes the milestones in the development of Oteseconazole leading to this first approval for reducing the incidence of RVVC in females with a history of RVVC who are NOT of reproductive potential.
Oteseconazole: an advance in treatment of recurrent vulvovaginal candidiasis
Future Microbiol 2021 Dec;16:1453-1461.PMID:34783586DOI:10.2217/fmb-2021-0173.
Recurrent vulvovaginal candidiasis (RVVC) has significant disease, financial and quality-of-life burdens, affects women from all strata of society worldwide, and lacks an approved therapeutic solution. Fluconazole emerged in 2004 as an antifungal for RVVC; it provides symptom control and has been accepted worldwide as a first-line treatment. Its limitations include the development of resistance and a high rate of vulvovaginal candidiasis recurrence after therapy cessation. There is now an improved treatment option on the horizon: Oteseconazole - a novel, oral, selective fungal cytochrome P450 enzyme 51 inhibitor, designed to avoid off-target toxicities. In clinical studies to date, Oteseconazole has demonstrated impressive efficacy, a positive tolerability profile and hope for a superior RVVC treatment option.
Phase 3 study evaluating the safety and efficacy of Oteseconazole in the treatment of recurrent vulvovaginal candidiasis and acute vulvovaginal candidiasis infections
Am J Obstet Gynecol 2022 Dec;227(6):880.e1-880.e11.PMID:35863457DOI:10.1016/j.ajog.2022.07.023.
Background: Recurrent vulvovaginal candidiasis affects nearly 138 million women globally each year. In the United States, fluconazole is considered the standard of care for acute vulvovaginal candidiasis, but until recently there was no US Food and Drug Administration-approved drug for the treatment of recurrent vulvovaginal candidiasis. Oteseconazole is a novel oral selective inhibitor of fungal lanosterol demethylase (sterol 14α-demethylase cytochrome P450, an enzyme required for fungal growth) approved for the treatment of recurrent vulvovaginal candidiasis. Objective: This study was conducted to evaluate the efficacy and safety of oral Oteseconazole (VT-1161) in the prevention of recurrent culture-verified acute vulvovaginal candidiasis episodes through 50 weeks in participants with recurrent vulvovaginal candidiasis and to compare the efficacy of Oteseconazole and fluconazole in the treatment of the presenting acute vulvovaginal candidiasis episode. Study design: Women and postmenarcheal girls aged ≥12 years with a history of recurrent vulvovaginal candidiasis (N=219) were enrolled at 38 US sites. Eligible participants presenting with an active vulvovaginal candidiasis infection entered an induction phase in which they were randomly assigned 2:1 to receive 600 mg oral Oteseconazole on day 1 and 450 mg on day 2, with matching placebo capsules, or to 3 sequential 150-mg oral doses (once every 72 hours) of fluconazole, with matching placebo capsules. Following the 2-week induction phase, the 185 participants with resolved acute vulvovaginal candidiasis infection (a clinical signs and symptoms score of <3) entered the maintenance phase and received 150 mg of Oteseconazole or placebo weekly for 11 weeks. Participants were observed for an additional 37 weeks. Results: In the induction phase, Oteseconazole was noninferior to fluconazole in the proportion of participants in the intent-to-treat population with resolved acute vulvovaginal candidiasis infection at the week 2 (day 14) test-of-cure visit, with 93.2% of participants on Oteseconazole vs 95.8% on fluconazole achieving resolution. In the maintenance phase, Oteseconazole was superior to placebo in the proportion of participants in the intent-to-treat population with ≥1 culture-verified acute vulvovaginal candidiasis episode through 50 weeks, 5.1% compared with 42.2%, respectively (P<.001). Overall, treatment-emergent adverse event rates were similar in both groups: 54% for participants who received Oteseconazole in the induction and maintenance phases vs 64% for participants who received fluconazole in the induction phase and placebo in the maintenance phase. Most treatment-emergent adverse events in each group were mild or moderate, with 3.4% of treatment-emergent adverse events graded as severe or higher in the Oteseconazole/Oteseconazole group vs 4.2% in FLUCONAZOLE/placebo group. Conclusion: In participants with recurrent vulvovaginal candidiasis, Oteseconazole was safe and efficacious in the treatment and prevention of recurrent acute vulvovaginal candidiasis episodes and was noninferior to vulvovaginal candidiasis standard-of-care fluconazole in the treatment of the presenting acute vulvovaginal candidiasis infection.
Novel antifungal agents in clinical trials
F1000Res 2021 Jun 28;10:507.PMID:35136573DOI:10.12688/f1000research.28327.2.
Invasive fungal diseases due to resistant yeasts and molds are an important and increasing public health threat, likely due to a growing population of immunosuppressed hosts, increases in antifungal resistance, and improvements in laboratory diagnostics. The significant morbidity and mortality associated with these pathogens bespeaks the urgent need for novel safe and effective therapeutics. This review highlights promising investigational antifungal agents in clinical phases of development: fosmanogepix, ibrexafungerp, rezafungin, encochleated amphotericin B, Oteseconazole (VT-1161), VT-1598, PC945, and olorofim. We discuss three first-in-class members of three novel antifungal classes, as well as new agents within existing antifungal classes with improved safety and tolerability profiles due to enhanced pharmacokinetic and pharmacodynamic properties.
Review of the alternative therapies for onychomycosis and superficial fungal infections: posaconazole, fosravuconazole, voriconazole, Oteseconazole
Int J Dermatol 2022 Dec;61(12):1431-1441.PMID:34882787DOI:10.1111/ijd.15999.
Terbinafine and itraconazole are the most commonly used oral antifungals to treat onychomycosis and superficial dermatomycoses. Recently, poor response to oral terbinafine has been reported. We have summarized the most appropriate dosing regimens of posaconazole, fosravuconazole, voriconazole, and Oteseconazole (VT-1161) to treat onychomycosis and superficial fungal infections. A structured search on PubMed and Google Scholar was conducted. Additionally, the bibliographies of selected articles were searched to identify relevant records. The number of records identified from the searches was 463, with 50 articles meeting the inclusion criteria for review. None of the new azoles are US FDA approved for onychomycosis treatment; however, an increasing number of studies have evaluated these agents. The efficacies (complete cure and mycologic cure) of the antifungal agents for dermatophyte great toenail onychomycosis treatment are terbinafine 250 mg/day × 12 weeks (Phase III trial) (38%, 70%), itraconazole 200 mg/day × 12 weeks (Phase III trial) (14%, 54%), posaconazole 200 mg/day × 24 weeks (Phase IIB) (54.1%, 70.3%), fosravuconazole 100 mg/day ravuconazole equivalent × 12 weeks (Phase III) (59.4%, 82.0%), and Oteseconazole 300 mg/day loading dose × 2 weeks (Phase II), followed by 300 mg/week × 10 weeks (maintenance dose) (45%, 70%). Guidelines for monitoring are also presented.