Linaclotide-d4

Linaclotide-d4 is intended for use as an internal standard for the quantification of linaclotide (Cay-24085) by GC- or LC-MS. Linaclotide is a peptide agonist of the guanylate cyclase C receptor (Ki = 16.4 nM in a radioligand binding assay using mouse intestinal mucosa). Luminal exposure to 5 µg of linaclotide stimulates fluid secretion and cGMP concentration in jejunal loops isolated from wild-type mice but not guanylate cyclase C receptor-null mice. Linaclotide (100 µg/kg) increases intestinal transit rate in wild-type mice. It also reduces the number of phosphorylated ERK-positive dorsal horn neurons in the thoracolumbar spinal cord, a marker of nociceptive signaling, following noxious colorectal distension and mechanical hypersensitivity in a mouse model of TNBS-induced colitis. Formulations containing linaclotide have been used for the treatment of constipation and pain associated with irritable bowel syndrome.Formal Name: ((3S,6R,15R,20R,23S,26R,29R,32R,37R,40S,45aS)-32-amino-40-(2-amino-2-oxoethyl)-26-(2-carboxyethyl)-23-(4-hydroxybenzyl)-9-((R)-1-hydroxyethyl)-3-(methyl-d3)-1,4,7,10,13,22,25,28,31,38,41,47-dodecaoxotetracontahydro-19H-37,20-(epiminomethano)-6,29-(methanodithiomethano)pyrrolo[2,1-s][1,2,27,28]tetrathia[5,8,11,14,17,20,23,32,35,38,41]undecaazacyclotritetracontine-15-carbonyl-3-d)-L-tyrosine. Molecular Formula: C59H75D4N15O21S6. Formula Weight: 1530.8. Purity: >99% deuterated forms (d1-d4). Formulation: (Request formulation change), A solid. Solubility: DMF: 30 mg/ml, DMSO: 30 mg/ml, DMSO:PBS (pH 7.2) (1:1): 0.2 mg/ml. SMILES: N[C@H](C(N[C@]1([H])C(N[C@H](CCC(O)=O)C2=O)=O)=O)CSSC[C@]([H])(NC3=O)C(N[C@@H](CC(N)=O)C(N4[C@@](C(N[C@@](C(N[C@](CSSC1)([H])C(NC([C@H](O)C)C(NCC(N[C@H](C(N[C@@H](CC5=CC=C(O)C=C5)C(O)=O)=O)CSSC[C@]3([H])NC([C@H](CC6=CC=C(O)C=C6)N2)=O)=O)=O)=O)=O)([2H])C([2H])([2H])[2H])=O)([H])CCC4)=O)=O. 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/i1D3,26D. InChi Key: KXGCNMMJRFDFNR-JVHSGDSASA-N.