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Purity: =98.97%
Linaclotide (trade name Linzess in the US and Mexico, and as Constella elsewhere) is a novel, potent, selective and orally administered, peptide agonist of guanylate cyclase C developed for the treatment of constipation-predominant irritable bowel syndrome (IBS-C) and chronic constipation. It has a black box warning regarding the possibility of severe dehydration in US children; gastrointestinal side effects are the most frequent in other cases.
| ln Vitro |
Linaclotide inhibits in vitro [125I]-STa binding to intestinal mucosal membranes from wt mice in a concentration-dependent manner. On the other hand, there is a significant decrease in [125I]-STa binding to these membranes from GC-C null mice. Linacelotide is totally broken down after 30 minutes of in vitro incubation in jejunal fluid[1]. Linaclotide improves defecation by increasing the secretion of water into the lumen and inhibiting the absorption of sodium ions through its action on guanylate cyclase-C receptors on the luminal membrane. The drug is only slightly absorbed into the systemic circulation[2].
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| ln Vivo |
Oral bioavailability is extremely low, according to pharmacokinetic analysis (0.10%). In models of intestinal secretion and transit, linaclotide shows notable pharmacological effects in wt mice, but not in GC-C null mice: elevated levels of cyclic guanosine-3',5-monophosphate are secreted along with accelerated gastrointestinal transit when increased fluid secretion is induced into surgically ligated jejunal loops[1]. In patients with chronic constipation, linaclotide reduces abdominal pain and significantly increases weekly spontaneous bowel movements and complete spontaneous bowel movements (CSBMs)[2].
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| Animal Protocol |
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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| References |
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| Molecular Formula |
C59H79N15O21S6
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|---|---|
| Molecular Weight |
1526.74000
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| Exact Mass |
1525.39
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| Elemental Analysis |
C, 46.41; H, 5.22; N, 13.76; O, 22.01; S, 12.60
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| CAS # |
851199-59-2
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| Related CAS # |
851199-60-5 (acetate); 851199-59-2
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| Appearance |
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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| Chemical Name |
(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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| Synonyms |
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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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
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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| Solubility (In Vitro) |
DMSO: ~50 mg/mL (~32.8 mM)
H2O: ~16.7 mg/mL (~10.9 mM) |
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| Solubility (In Vivo) |
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). |
| Preparing Stock Solutions | 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 |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| 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 |
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