Dolcanatide

Synopsis, Chemistry

DIGITAL CONTENT

1 News

1 News

Product Search

API SUPPLIERS

API Suppliers

US DMFs Filed

CEP/COS Certifications

JDMFs Filed

EU WC

Listed Suppliers

API REF. PRICE (USD / KG)

API Market Place

INTERMEDIATES

DOSSIERS // FDF

USA (Orange Book)

Europe

Canada

Australia

South Africa

Uploaded Dossiers

GLOBAL SALES (USD Million)

U.S. Medicaid

Annual Reports

FDF Market Place

EXCIPIENTS

PATENTS & EXCLUSIVITIES

USFDA Orange Book Patents

USFDA Exclusivities

DIGITAL CONTENT

Blog #PharmaFlow

News

REF STANDARD

EDQM

USP

Other Listed Suppliers

SERVICES

Also known as: Dolcanatide [usan], Unii-wu977t914k, Gtpl10011, Wu977t914k, Hy-p3499, 1092457-65-2

Molecular Formula

C₆₅H₁₀₄N₁₈O₂₆S₄

Molecular Weight

1681.9 g/mol

InChI Key

NSPHQWLKCGGCQR-HLHYUOOASA-N

Dolcanatide is an orally administered analog of the human endogenous natriuretic hormone uroguanylin and guanylate cyclase C (GC-C) agonist, with potential laxative, anti-nociceptive and anti-inflammatory activities. Upon administration, dolcanatide, by mimicking uroguanylin, binds to and activates GC-C locally on endothelial cells in the gastrointestinal (GI) tract, without entering the systemic circulation. Activation of GC-C results in an increase in cyclic guanosine monophosphate (cGMP). Increased concentrations of cGMP lead to the activation of the anion channel cystic fibrosis transmembrane conductance regulator (CFTR). CFTR activation increases the secretion of negatively charged ions, particularly chloride and bicarbonate, into the GI tract lumen, which further drives sodium ions and then water into the lumen. This leads to increased fluid secretion in the GI tract, accelerated transit and changes in stool consistency. In addition, ion channel modulation may decrease muscle contractions and the activity of pain-sensing nerves, thereby decreasing intestinal pain. Also, GC-C may inhibit the secretion of pro-inflammatory cytokines, which may ameliorate GI inflammation. Uroguanylin, a naturally occurring human GI peptide, is a ligand for GC-C and plays a key role in anti-inflammatory processes in the GI tract.

1 2D Structure

Dolcanatide

2 Identification

2.1 Computed Descriptors

2.1.1 IUPAC Name

(2R)-2-[[(1R,4S,7S,10S,13S,16R,19S,22S,25R,32S,38R)-10-(2-amino-2-oxoethyl)-25-[[(2S)-4-carboxy-2-[[(2S)-3-carboxy-2-[[(2R)-2,4-diamino-4-oxobutanoyl]amino]propanoyl]amino]butanoyl]amino]-22-(2-carboxyethyl)-32-[(1R)-1-hydroxyethyl]-4-methyl-19-(2-methylpropyl)-3,6,9,12,15,18,21,24,30,33,36-undecaoxo-7,13-di(propan-2-yl)-27,28,40,41-tetrathia-2,5,8,11,14,17,20,23,31,34,37-undecazabicyclo[14.13.13]dotetracontane-38-carbonyl]amino]-4-methylpentanoic acid

2.1.2 InChI

InChI=1S/C65H104N18O26S4/c1-25(2)15-34-55(98)80-41-24-113-110-21-38(58(101)77-37(65(108)109)16-26(3)4)71-44(87)20-69-62(105)50(30(10)84)83-61(104)40(78-51(94)29(9)70-63(106)48(27(5)6)81-57(100)35(18-43(68)86)76-64(107)49(28(7)8)82-60(41)103)23-112-111-22-39(59(102)73-32(53(96)75-34)11-13-45(88)89)79-54(97)33(12-14-46(90)91)72-56(99)36(19-47(92)93)74-52(95)31(66)17-42(67)85/h25-41,48-50,84H,11-24,66H2,1-10H3,(H2,67,85)(H2,68,86)(H,69,105)(H,70,106)(H,71,87)(H,72,99)(H,73,102)(H,74,95)(H,75,96)(H,76,107)(H,77,101)(H,78,94)(H,79,97)(H,80,98)(H,81,100)(H,82,103)(H,83,104)(H,88,89)(H,90,91)(H,92,93)(H,108,109)/t29-,30+,31+,32-,33-,34-,35-,36-,37+,38-,39-,40-,41-,48-,49-,50-/m0/s1

2.1.3 InChI Key

NSPHQWLKCGGCQR-HLHYUOOASA-N

2.1.4 Canonical SMILES

CC1C(=O)NC2CSSCC(C(=O)NC(C(=O)NC(C(=O)NC(CSSCC(NC(=O)CNC(=O)C(NC2=O)C(C)O)C(=O)NC(CC(C)C)C(=O)O)C(=O)NC(C(=O)NC(C(=O)NC(C(=O)N1)C(C)C)CC(=O)N)C(C)C)CC(C)C)CCC(=O)O)NC(=O)C(CCC(=O)O)NC(=O)C(CC(=O)O)NC(=O)C(CC(=O)N)N

2.1.5 Isomeric SMILES

C[C@H]1C(=O)N[C@H]2CSSC[C@@H](C(=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](CC(C)C)C(=O)O)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N1)C(C)C)CC(=O)N)C(C)C)CC(C)C)CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@@H](CC(=O)N)N

2.2 Synonyms

2.2.1 MeSH Synonyms

1. Sp-333

2.2.2 Depositor-Supplied Synonyms

1. Dolcanatide [usan]

2. Unii-wu977t914k

3. Gtpl10011

4. Wu977t914k

5. Hy-p3499

6. 1092457-65-2

7. D-leucine, D-asparaginyl-l-alpha-aspartyl-l-alpha-glutamyl-l-cysteinyl-l-alpha-glutamyl-l-leucyl-l-cysteinyl-l-valyl-l-asparaginyl-l-valyl-l-alanyl-l-cysteinyl-l-threonylglycyl-l-cysteinyl-, Cyclic (4->12),(7->15)-bis(disulfide)

8. Cs-0615000

2.3 Create Date

2015-08-15

3 Chemical and Physical Properties

Molecular Formula	C₆₅H₁₀₄N₁₈O₂₆S₄
Molecular Weight	1681.9 g/mol
XLogP3	-8.2
Hydrogen Bond Donor Count	23
Hydrogen Bond Acceptor Count	31
Rotatable Bond Count	28
Exact Mass	1680.6252002 g/mol
Monoisotopic Mass	1680.6252002 g/mol
Topological Polar Surface Area	819 Å²
Heavy Atom Count	113
Formal Charge	0
Complexity	3490
Isotope Atom Count	0
Defined Atom Stereocenter Count	16
Undefined Atom Stereocenter Count	0
Defined Bond Stereocenter Count	0
Undefined Bond Stereocenter Count	0
Covalently Bonded Unit Count	1