(1→3)-β-D-glucan synthase

体外活性：A的孵育。 fumigatu与单剂量的卡泊芬净影响相同比例的顶端和顶端下分支细胞长达72小时。A内新细胞壁合成的活性中心的细胞。熏菌菌丝暴露于卡泊芬净后会被杀死。醋酸卡泊芬净不可逆地抑制 1,3-β-D-葡聚糖合成酶，阻止葡聚糖聚合物的形成并破坏真菌细胞壁的完整性。醋酸卡泊芬净的消除半衰期为9-10小时。卡泊芬净显示出抗曲霉菌的活性。以及各种念珠菌。醋酸卡泊芬净对白色念珠菌和热带念珠菌分离株的生长动力学研究表明，醋酸卡泊芬净在 0.06 至 1 μg/ml 浓度范围内（0.25 至 4 倍）在 3 至 7 小时内表现出杀菌活性（即活力降低 99%）。 MIC)[4]。醋酸卡泊芬净对念珠菌抑制90%的最低抑菌浓度如下：C.白色念珠菌 0.5 μg/mL（范围，0.25-0.5）、光滑念珠菌 1.0 μg/mL（范围，0.25-2.0）、热带念珠菌 1.0 μg/mL（范围，0.25-1.0）、近光滑念珠菌 0.5 μg/mL （范围，0.25-1.0）和克柔梭菌 2.0 μg/mL（范围，0.5-2.0）。激酶测定：醋酸卡泊芬净是一种抗真菌药物，可非竞争性抑制 1,3-β-d 葡聚糖合酶活性。细胞测定：卡泊芬净抑制细胞壁β-1,3-葡聚糖的合成，从而引发几丁质合成的代偿性刺激。卡泊芬净诱导熏曲霉的形态变化。此外，用卡泊芬净处理可诱导 ChsG 依赖性几丁质合成上调，并在烟曲霉中形成富含几丁质的微菌落。

玻璃体注射浓度为 0.41 至 4.1 μM 的卡泊芬净的小鼠，其 ERG 波形没有显着改变，并且其视网膜没有可检测到的形态变化或细胞损失。在玻璃体浓度为 41 μM 时，卡泊芬净降低了 ERG 的 a 波、b 波和暗视阈值反应的幅度，并且还导致神经节细胞层中的细胞数量减少。从感染后 30 小时开始，每天一次腹膜内注射卡泊芬净 (8 mg/kg) 或 1 mg/kg 两性霉素 B，持续 7 天，相对于载体对照治疗，第 28 天的存活率为 100%，这导致每日死亡率为 100% 11 传染性挑战后。与第 5 天对照负荷达到峰值时的载体对照治疗相比，卡泊芬净减少了肾脏和脑组织中活念珠菌的回收。在第 5 天，接受 2 mg/kg 或更高剂量的卡泊芬净治疗的小鼠的脑负担显着低于两性霉素 B 治疗的小鼠。两性霉素 B 和卡泊芬净治疗可将肾脏真菌负担减少 1.7 log CFU/g 和 2.46 至 3.64 log CFU/g。分别为g。

棘白菌素MK-0991，原名L-743872，是一种水溶性脂肽，已在临床前研究中证明对念珠菌、烟曲霉和卡氏肺孢子虫具有有效活性。对MK-0991进行了广泛的体外生物学评估，以更好地确定这种新型化合物的潜在活性。使用MK-0991对大约200个念珠菌、新生隐球菌和曲霉菌临床分离株进行药敏试验，以确定MIC和最小杀真菌浓度MF（s）。对40个白色念珠菌临床分离株，90%的分离株被抑制的MFC为0.5微克/毫升。对念珠菌和新生隐球菌分离株的抗真菌药物耐药性菌株进行的敏感性测试表明，这些分离株的MK-0991 MFC与易感分离株的MFC相当。MK-0991对白色念珠菌和热带假丝酵母分离株的生长动力学研究表明，该化合物在0.06至1微克/毫升（MIC的0.25至4倍）的浓度下，在3至7小时内表现出杀真菌活性（即活力降低99%）。MK-0991与两性霉素B的药物组合研究发现，该组合在体外对白色念珠菌、新生隐球菌或烟曲霉没有拮抗作用。对0-50%的人或小鼠混合血清的研究证实，真菌对MK-0991的易感性不受人或小鼠血清存在的显著影响。耐药性诱导研究的结果表明，反复暴露（40代）MK-0991不会改变白色念珠菌的易感性。用MK-0991对洗涤和未洗涤的人或小鼠红细胞进行的红细胞溶血研究表明，该化合物的溶血潜力最小。临床前研究的这些有利结果支持MK-0991在人类身上的进一步研究。[2]

用卡泊芬净涂布微量滴定板的孔对白色念珠菌生物膜形成的影响。使用改良的测定法，其中微量滴定板的孔直接用卡泊芬净预涂，以研究该药物防止生物膜形成的能力。简言之，将无菌PBS中不同浓度的200μl体积的卡泊芬净加入微量滴定板的选定孔中，并在4°C下孵育过夜。孵育后，吸取过量的卡泊芬净，并在无菌PBS中洗涤平板一次。白色念珠菌3153A细胞在PBS中清洗，并以每毫升106个细胞的浓度重悬在RPMI 1640中。然后在96孔微量滴定板上接种悬浮液（每孔100μl），并在37°C下孵育24小时，以形成生物膜。在无菌PBS中抽吸和洗涤孔的内容物三次，并通过XTT还原测定和光学显微镜评估生物膜形成的程度。对于XTT测定，卡泊芬净的抑制作用表示为卡泊芬素处理的孔与对照（塑料）孔相比的光密度（OD）的百分比。采用Student t检验进行统计分析。P值<0.05被认为具有统计学意义。使用Prism 3.00版Window进行分析。[3]

1, 2, 4, or 8 mg/kg/day; i.p.
Mice

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Rhizopus oryzae is the most common cause of zygomycosis, a life-threatening infection that usually occurs in patients with diabetic ketoacidosis. Despite standard therapy, the overall rate of mortality from zygomycosis remains >50%, and new strategies for treatment are urgently needed. The activities of caspofungin acetate (CAS) and other echinocandins (antifungal inhibitors of the synthesis of 1,3-beta-D-glucan synthase [GS]) against the agents of zygomycosis have remained relatively unexplored, especially in animal models of infection. We found that R. oryzae has both an FKS gene, which in other fungi encodes a subunit of the GS synthesis complex, and CAS-susceptible, membrane-associated GS activity. Low-dose but not high-dose CAS improved the survival of mice with diabetic ketoacidosis infected with a small inoculum but not a large inoculum of R. oryzae. Fungal burden, assessed by a novel quantitative PCR assay, correlated with increasing inocula and progression of disease, particularly later in the infection, when CFU counts did not. CAS decreased the brain burden of R. oryzae when it was given prophylactically but not when therapy was started after infection. These results indicate that CAS has significant but limited activity against R. oryzae in vivo and demonstrates an inverse dose-response effect. The potential for CAS to play a role in combination therapy against zygomycosis merits further investigation.[4]
The inhibition of R. oryzae GS by CAS (caspofungin acetate ) and the discovery of an FKS homolog demonstrate that the drug target is present in this organism. CAS might be effective against R. oryzae in vivo, despite the high MIC, especially given the known constraints of MIC testing with molds (13, 29). The in vivo efficacy of CAS was tested in diabetic ketoacidotic mice infected with R. oryzae. Intravenous treatment with AMB (0.5 mg/kg b.i.d.) or CAS (0.5, 2.5, or 5 mg/kg b.i.d.) was initiated 24 h after the mice were infected with 5 × 102 or 5 × 103 spores of R. oryzae. At 0.5 mg/kg b.i.d., CAS, but not AMB, improved the survival of mice infected with 5 × 102 spores of R. oryzae compared to that of the infected untreated mice (P = 0.049) (Fig.2a). Eighty percent of the diabetic mice treated with CAS at 0.5 mg/kg/day were alive 10 days after infection, whereas 30% of the infected untreated mice were alive at that time. Surprisingly, higher doses of CAS (2.5 or 5 mg/kg b.i.d.) did not improve the rate of survival. These results indicate that CAS has significant but limited activity against R. oryzae in vivo and demonstrates an inverse dose-response effect. [4]

Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
No information is available on the use of caspofungin during breastfeeding. Because caspofungin is 97% bound to plasma proteins and has poor oral bioavailability, it is unlikely to reach the milk and be absorbed by the infant. Caspofungin can safely be given intravenously to infants of aged 3 months or older. Any amount absorbed from milk is likely to be far less than an infant dose. If caspofungin is required by the mother, it is not a reason to discontinue breastfeeding.
◉ Effects in Breastfed Infants
Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.

[1]. Crit Care Med.2003 May;31(5):1577-8;
[2]. Antimicrob Agents Chemother.1997 Nov;41(11):2326-32.
[3]. Antimicrob Agents Chemother. 2002 Nov; 46(11): 3591–3596.
[4]. Antimicrob Agents Chemother. 2005 Feb; 49(2): 721–727.

Caspofungin Acetate is the acetate salt of an antimycotic echinocandin lipopeptide, semisynthetically derived from a fermentation product of the fungus Glarea lozoyensis. Caspofungin inhibits 1,3-beta-glucan synthase, resulting in decreased synthesis of beta(1,3)-D-glucan (an essential component of the fungal cell wall), weakening of the fungal cell wall, and fungal cell wall rupture. This agent is active against Aspergillus and Candida species.
A cyclic lipopeptide echinocandin and beta-(1,3)-D-glucan synthase inhibitor that is used to treat internal or systemic MYCOSES.
See also: Caspofungin (has active moiety).

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Drug Indication
Treatment of invasive candidiasis in adult or paediatric patients. Treatment of invasive aspergillosis in adult or paediatric patients who are refractory to or intolerant of amphotericin B, lipid formulations of amphotericin B and/or itraconazole. Refractoriness is defined as progression of infection or failure to improve after a minimum of 7 days of prior therapeutic doses of effective antifungal therapy. Empirical therapy for presumed fungal infections (such as Candida or Aspergillus) in febrile, neutropaenic adult or paediatric patients.
Fungal infections

C56H96N10O19

1213.42

1092.64

C, 55.43; H, 7.97; N, 11.54; O, 25.05

179463-17-3

Caspofungin;162808-62-0;Caspofungin-d4 acetate; 162808-62-0; 179463-17-3 (acetate)

16119813

White to off-white solid powder

1408.1ºC at 760 mmHg

0mmHg at 25°C

0.061

412.03

18

22

23

85

1930

16

O=C1[C@@]([H])(NC([C@@]([H])(NC([C@]2([H])C[C@H](CN2C([C@@]([H])(NC([C@H](C[C@H]([C@H](NC([C@]2([H])[C@H](CCN21)O)=O)NCCN)O)NC(=O)CCCCCCCC[C@@H](C)C[C@@H](C)CC)=O)[C@H](O)C)=O)O)=O)[C@H](O)[C@H](C1C=CC(=CC=1)O)O)=O)[C@H](O)CCN.C(=O)(O)C.C(=O)(O)C

OGUJBRYAAJYXQP-AVOYSFSSSA-N

InChI=1S/C52H88N10O15.2C2H4O2/c1-5-28(2)24-29(3)12-10-8-6-7-9-11-13-39(69)56-34-26-38(68)46(55-22-21-54)60-50(75)43-37(67)19-23-61(43)52(77)41(36(66)18-20-53)58-49(74)42(45(71)44(70)31-14-16-32(64)17-15-31)59-48(73)35-25-33(65)27-62(35)51(76)40(30(4)63)57-47(34)72;2*1-2(3)4/h14-17,28-30,33-38,40-46,55,63-68,70-71H,5-13,18-27,53-54H2,1-4H3,(H,56,69)(H,57,72)(H,58,74)(H,59,73)(H,60,75);2*1H3,(H,3,4)/t28-,29+,30-,33-,34+,35+,36-,37+,38+,40+,41-,42+,43+,44+,45+,46+;;/m1../s1

(10S,12R)-N-((2R,6S,9S,11S,12S,14aS,15S,20R,23S,25aS)-20-((R)-3-amino-1-hydroxypropyl)-12-((2-aminoethyl)amino)-23-((1S,2S)-1,2-dihydroxy-2-(4-hydroxyphenyl)ethyl)-2,11,15-trihydroxy-6-((R)-1-hydroxyethyl)-5,8,14,19,22,25-hexaoxotetracosahydro-1H-dipyrrolo[2,1-c:2',1'-l][1,4,7,10,13,16]hexaazacyclohenicosin-9-yl)-10,12-dimethyltetradecanamide diacetate

L743872; L-743872; L 743872; MK 0991; MK-0991; MK0991; Caspofungin acetate; brand name: Cancidas.

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

注意： 请将本产品存放在密封且受保护的环境中（例如氮气保护），避免吸湿/受潮和光照。

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : 100 mg/mL ( 82.41 mM )
Water : 50~100 mg/mL (~82.41 mM )

配方 1 中的溶解度: ≥ 2.5 mg/mL (2.06 mM) (饱和度未知) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 25.0 mg/mL澄清DMSO储备液加入900 μL 20% SBE-β-CD生理盐水溶液中，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

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配方 2 中的溶解度: ≥ 2.08 mg/mL (1.71 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 20.8 mg/mL澄清的DMSO储备液加入到400 μL PEG300中，混匀；再向上述溶液中加入50 μL Tween-80，混匀；然后加入450 μL生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 3 中的溶解度: ≥ 2.08 mg/mL (1.71 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 20.8 mg/mL 澄清 DMSO 储备液加入到 900 μL 玉米油中并混合均匀。

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配方 4 中的溶解度: 10% DMSO+90% (20% SBE-β-CD in Saline): ≥ 2.5 mg/mL (2.06 mM)

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配方 5 中的溶解度: 100 mg/mL (82.41 mM) in PBS (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液; 超声助溶.

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。