规格 | 价格 | 库存 | 数量 |
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10 mM * 1 mL in DMSO |
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1mg |
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2mg |
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5mg |
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10mg |
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25mg |
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Other Sizes |
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体外研究 (In Vitro) |
Linaclotide 以浓度依赖性方式在体外抑制 [125I]-STa 与野生型小鼠肠粘膜的结合。相反,GC-C 无效小鼠的[125I]-STa 与这些膜的结合显着减少。在体外空肠液中孵育 30 分钟后,利那洛肽完全降解[1]。利那洛肽作用于管腔膜上的鸟苷酸环化酶-C受体,增加肠道内氯化物和碳酸氢盐的分泌,抑制钠离子的吸收,从而增加管腔内水分的分泌,改善排便;该药物被最低限度地吸收到体循环中[2]。
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体内研究 (In Vivo) |
药代动力学分析显示口服生物利用度非常低(0.10%)。在肠道分泌和运输模型中,利那洛肽在野生型小鼠中表现出显着的药理作用,但在 GC-C 缺失小鼠中则不然:诱导手术结扎的空肠环中液体分泌增加,伴随着环状鸟苷-3',5 水平的分泌升高-单磷酸盐和加速胃肠道转运[1]。利那洛肽显着增加每周自发排便和完全自发排便 (CSBM),同时减少慢性便秘患者的腹痛[2]。
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动物实验 |
Mice: Three groups (n=3) of female CD-1 mice receive linaclotide (8 mg/kg) intravenously (i.v.), and two groups (n=3) receive linaclotide (8 mg/kg) by gavage (p.o.) in order to assess oral bioavailability. After allowing blood to clot for five minutes, serum is collected and kept at -80°C until sample preparation and LC-MS/MS analysis[1]. The blood is then centrifuged at 13,000×g for three minutes.
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参考文献 |
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分子式 |
C59H79N15O21S6
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分子量 |
1526.74000
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精确质量 |
1525.39
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元素分析 |
C, 46.41; H, 5.22; N, 13.76; O, 22.01; S, 12.60
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CAS号 |
851199-59-2
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相关CAS号 |
851199-60-5 (acetate); 851199-59-2
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外观&性状 |
Solid powder
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SMILES |
C[C@H]1C(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CSSC[C@H](NC(=O)CNC(=O)[C@@H](NC2=O)[C@@H](C)O)C(=O)N[C@@H](CC4=CC=C(C=C4)O)C(=O)O)C(=O)N[C@@H](CSSC[C@@H](C(=O)N3)N)C(=O)N[C@H](C(=O)N5CCC[C@H]5C(=O)N1)CC(=O)N)CC6=CC=C(C=C6)O)CCC(=O)O
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InChi Key |
KXGCNMMJRFDFNR-WDRJZQOASA-N
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InChi Code |
InChI=1S/C59H79N15O21S6/c1-26-47(82)69-41-25-101-99-22-38-52(87)65-33(13-14-45(80)81)49(84)66-34(16-28-5-9-30(76)10-6-28)50(85)71-40(54(89)72-39(23-97-96-20-32(60)48(83)70-38)53(88)67-35(18-43(61)78)58(93)74-15-3-4-42(74)56(91)63-26)24-100-98-21-37(64-44(79)19-62-57(92)46(27(2)75)73-55(41)90)51(86)68-36(59(94)95)17-29-7-11-31(77)12-8-29/h5-12,26-27,32-42,46,75-77H,3-4,13-25,60H2,1-2H3,(H2,61,78)(H,62,92)(H,63,91)(H,64,79)(H,65,87)(H,66,84)(H,67,88)(H,68,86)(H,69,82)(H,70,83)(H,71,85)(H,72,89)(H,73,90)(H,80,81)(H,94,95)/t26-,27+,32-,33-,34-,35-,36-,37-,38-,39-,40-,41-,42-,46-/m0/s1
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化学名 |
(2S)-2-[[(1R,4S,7S,13S,16R,21R,24R,27S,30S,33R,38R,44S)-21-amino-13-(2-amino-2-oxoethyl)-27-(2-carboxyethyl)-44-[(1R)-1-hydroxyethyl]-30-[(4-hydroxyphenyl)methyl]-4-methyl-3,6,12,15,22,25,28,31,40,43,46,51-dodecaoxo-18,19,35,36,48,49-hexathia-2,5,11,14,23,26,29,32,39,42,45,52-dodecazatetracyclo[22.22.4.216,33.07,11]dopentacontane-38-carbonyl]amino]-3-(4-hydroxyphenyl)propanoic acid
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别名 |
MM 416775; MM416775; MD-1100 acetate; MM-416775; Linzess; Linaclotide acetate; Linzess Constela
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HS Tariff Code |
2934.99.9001
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存储方式 |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
运输条件 |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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溶解度 (体外) |
DMSO: ~50 mg/mL (~32.8 mM)
H2O: ~16.7 mg/mL (~10.9 mM) |
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溶解度 (体内) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (1.64 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (1.64 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C,1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (1.64 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 4.17 mg/mL (2.73 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication (<60°C). 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。 |
制备储备液 | 1 mg | 5 mg | 10 mg | |
1 mM | 0.6550 mL | 3.2750 mL | 6.5499 mL | |
5 mM | 0.1310 mL | 0.6550 mL | 1.3100 mL | |
10 mM | 0.0655 mL | 0.3275 mL | 0.6550 mL |
1、根据实验需要选择合适的溶剂配制储备液 (母液):对于大多数产品,InvivoChem推荐用DMSO配置母液 (比如:5、10、20mM或者10、20、50 mg/mL浓度),个别水溶性高的产品可直接溶于水。产品在DMSO 、水或其他溶剂中的具体溶解度详见上”溶解度 (体外)”部分;
2、如果您找不到您想要的溶解度信息,或者很难将产品溶解在溶液中,请联系我们;
3、建议使用下列计算器进行相关计算(摩尔浓度计算器、稀释计算器、分子量计算器、重组计算器等);
4、母液配好之后,将其分装到常规用量,并储存在-20°C或-80°C,尽量减少反复冻融循环。
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)。如该浓度超过该批次药物DMSO溶解度,请首先与我们联系。
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 ddH2O,混匀澄清。
(1) 请确保溶液澄清之后,再加入下一种溶剂 (助溶剂) 。可利用涡旋、超声或水浴加热等方法助溶;
(2) 一定要按顺序加入溶剂 (助溶剂) 。
NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
NCT03796884 | Active Recruiting |
Drug: Linaclotide Other: Placebo |
Colorectal Adenoma Stage 0 Colorectal Cancer AJCC v8 |
Sidney Kimmel Cancer Center at Thomas Jefferson University |
October 30, 2019 | Phase 2 |
NCT03119584 | Active Recruiting |
Drug: linaclotide or placebo | Chronic Constipation Diabete Mellitus |
Texas Tech University Health Sciences Center, El Paso |
September 1, 2015 | Phase 4 |
NCT05652205 | Recruiting | Drug: Linaclotide Drug: Placebo for Linaclotide |
Chronic Idiopathic Constipation (CIC) Functional Constipation (FC) |
AbbVie | December 29, 2022 | Phase 3 |
NCT06091735 | Recruiting | Drug: OSS Drug: OSS+Linzess Drug: PEG-Interferon Alfa |
Bowel Preparation | Jinling Hospital, China | August 1, 2023 | Not Applicable |
NCT05760313 | Recruiting | Drug: Linaclotide Drug: Placebo |
Functional Constipation | AbbVie | April 27, 2023 | Phase 2 |