Larazotide | CAS#258818-34-7 | tight junction regulator

MedKoo Cat#: 598398 | Name: Larazotide

Description:

WARNING: This product is for research use only, not for human or veterinary use.

Larazotide, also known as AT-1001, is a tight junction (TJ) regulator and reverses leaky junctions to their normally closed state. It is being studied in people with celiac disease. Larazotide promoted TJ assembly in a calcium switch assay. Larazotide acetate also promoted actin rearrangement, and junctional distribution of zonula occludens-1 (ZO-1), occludin, claudins, and E-cadherin. Larazotide promoted TJ maturation and decreased paracellular permeability in "leaky" Caco-2 cells. Taken together, our data indicate that larazotide acetate enhances TJ assembly and barrier function by promoting actin rearrangement and redistribution of TJ and AJ proteins.

Chemical Structure

Larazotide

CAS#258818-34-7 (free base)

Theoretical Analysis

MedKoo Cat#: 598398

Name: Larazotide

CAS#: 258818-34-7 (free base)

Chemical Formula: C32H55N9O10

Exact Mass: 725.4072

Molecular Weight: 725.84

Elemental Analysis: C, 52.95; H, 7.64; N, 17.37; O, 22.04

Price and Availability

This product is currently not in stock but may be available through custom synthesis. To ensure cost efficiency, the minimum order quantity is 1 gram. The estimated lead time is 2 to 4 months, with pricing dependent on the complexity of the synthesis (typically high for intricate chemistries). Quotes for quantities below 1 gram will not be provided. To request a quote, please click the button below. Note: If this product becomes available in stock in the future, pricing will be listed accordingly.

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Related CAS #

258818-34-7 (free base) 881851-50-9 (acetate)

Synonym

Larazotide; AT-2347; AT 2347; AT2347; AT-1001; AT 1001; AT1001;

IUPAC/Chemical Name

glycylglycyl-L-valyl-L-leucyl-L-valyl-L-glutaminyl-L-prolylglycine

InChi Key

ORFLZNAGUTZRLQ-ZMBVWFSWSA-N

InChi Code

InChI=1S/C32H55N9O10/c1-16(2)12-20(38-30(49)26(17(3)4)39-24(44)14-35-23(43)13-33)28(47)40-27(18(5)6)31(50)37-19(9-10-22(34)42)32(51)41-11-7-8-21(41)29(48)36-15-25(45)46/h16-21,26-27H,7-15,33H2,1-6H3,(H2,34,42)(H,35,43)(H,36,48)(H,37,50)(H,38,49)(H,39,44)(H,40,47)(H,45,46)/t19-,20-,21-,26-,27-/m0/s1

SMILES Code

CC(C[C@@H](C(N[C@H](C(N[C@H](C(N1CCC[C@H]1C(NCC(O)=O)=O)=O)CCC(N)=O)=O)C(C)C)=O)NC([C@H](C(C)C)NC(CNC(CN)=O)=O)=O)C

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO

Shelf Life

>3 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.03.00

More Info

Instruction

View handling instruction

Preparing Stock Solutions

The following data is based on the product molecular weight 725.84 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

1: Yonker LM, Swank Z, Gilboa T, Senussi Y, Kenyon V, Papadakis L, Boribong BP, Carroll RW, Walt DR, Fasano A. Zonulin Antagonist, Larazotide (AT1001), As an Adjuvant Treatment for Multisystem Inflammatory Syndrome in Children: A Case Series. Crit Care Explor. 2022 Feb 18;10(2):e0641. doi: 10.1097/CCE.0000000000000641. PMID: 35211683; PMCID: PMC8860335. 2: Caliskan AR, Gul M, Yılmaz I, Otlu B, Uremis N, Uremis MM, Kilicaslan I, Gul S, Tikici D, Saglam O, Yalcin M, Demirel U, Harputluoglu M. Effects of larazotide acetate, a tight junction regulator, on the liver and intestinal damage in acute liver failure in rats. Hum Exp Toxicol. 2021 Dec;40(12_suppl):S693-S701. doi: 10.1177/09603271211058882. Epub 2021 Nov 18. PMID: 34791921. 3: Di Micco S, Musella S, Sala M, Scala MC, Andrei G, Snoeck R, Bifulco G, Campiglia P, Fasano A. Peptide Derivatives of the Zonulin Inhibitor Larazotide (AT1001) as Potential Anti SARS-CoV-2: Molecular Modelling, Synthesis and Bioactivity Evaluation. Int J Mol Sci. 2021 Aug 30;22(17):9427. doi: 10.3390/ijms22179427. PMID: 34502335; PMCID: PMC8431481. 4: Hoilat GJ, Altowairqi AK, Ayas MF, Alhaddab NT, Alnujaidi RA, Alharbi HA, Alyahyawi N, Kamal A, Alhabeeb H, Albazee E, Almustanyir S, Abu-Zaid A. Larazotide acetate for treatment of celiac disease: A systematic review and meta-analysis of randomized controlled trials. Clin Res Hepatol Gastroenterol. 2022 Jan;46(1):101782. doi: 10.1016/j.clinre.2021.101782. Epub 2021 Jul 31. PMID: 34339872. 5: Slifer ZM, Hernandez L, Pridgen TA, Carlson AR, Messenger KM, Madan J, Krishnan BR, Laumas S, Blikslager AT. Larazotide acetate induces recovery of ischemia-injured porcine jejunum via repair of tight junctions. PLoS One. 2021 Apr 22;16(4):e0250165. doi: 10.1371/journal.pone.0250165. PMID: 33886649; PMCID: PMC8061941. 6: Slifer ZM, Krishnan BR, Madan J, Blikslager AT. Larazotide acetate: a pharmacological peptide approach to tight junction regulation. Am J Physiol Gastrointest Liver Physiol. 2021 Jun 1;320(6):G983-G989. doi: 10.1152/ajpgi.00386.2020. Epub 2021 Apr 21. PMID: 33881350. 7: Enomoto H, Yeatts J, Carbajal L, Krishnan BR, Madan JP, Laumas S, Blikslager AT, Messenger KM. In vivo assessment of a delayed release formulation of larazotide acetate indicated for celiac disease using a porcine model. PLoS One. 2021 Apr 12;16(4):e0249179. doi: 10.1371/journal.pone.0249179. PMID: 33844694; PMCID: PMC8041193. 8: Armandi A, Pellicano R, Caviglia GP. Tight junction regulation in celiac disease: role of larazotide acetate. Minerva Gastroenterol (Torino). 2022 Mar;68(1):4-6. doi: 10.23736/S2724-5985.21.02838-5. Epub 2021 Apr 1. PMID: 33793152. 9: Di Micco S, Musella S, Scala MC, Sala M, Campiglia P, Bifulco G, Fasano A. In silico Analysis Revealed Potential Anti-SARS-CoV-2 Main Protease Activity by the Zonulin Inhibitor Larazotide Acetate. Front Chem. 2021 Jan 15;8:628609. doi: 10.3389/fchem.2020.628609. PMID: 33520943; PMCID: PMC7843458. 10: Troisi J, Venutolo G, Terracciano C, Carri MD, Di Micco S, Landolfi A, Fasano A. The Therapeutic use of the Zonulin Inhibitor AT-1001 (Larazotide) for a Variety of Acute and Chronic Inflammatory Diseases. Curr Med Chem. 2021;28(28):5788-5807. doi: 10.2174/0929867328666210104110053. PMID: 33397225. 11: Storr M. Larazotid als Option bei Versagen einer glutenfreien Diät [Larazotide as an option in case of failure of a gluten-free diet]. Med Monatsschr Pharm. 2016 Feb;39(2):89-90. German. PMID: 26983338. 12: Khaleghi S, Ju JM, Lamba A, Murray JA. The potential utility of tight junction regulation in celiac disease: focus on larazotide acetate. Therap Adv Gastroenterol. 2016 Jan;9(1):37-49. doi: 10.1177/1756283X15616576. PMID: 26770266; PMCID: PMC4699279. 13: Leffler DA, Kelly CP, Green PH, Fedorak RN, DiMarino A, Perrow W, Rasmussen H, Wang C, Bercik P, Bachir NM, Murray JA. Larazotide acetate for persistent symptoms of celiac disease despite a gluten-free diet: a randomized controlled trial. Gastroenterology. 2015 Jun;148(7):1311-9.e6. doi: 10.1053/j.gastro.2015.02.008. Epub 2015 Feb 13. PMID: 25683116; PMCID: PMC4446229. 14: Kelly CP, Green PH, Murray JA, Dimarino A, Colatrella A, Leffler DA, Alexander T, Arsenescu R, Leon F, Jiang JG, Arterburn LA, Paterson BM, Fedorak RN; Larazotide Acetate Celiac Disease Study Group. Commentary: larazotide acetate - an exciting new development for coeliac patients? Authors' reply. Aliment Pharmacol Ther. 2013 Feb;37(4):496-7. doi: 10.1111/apt.12196. PMID: 23336684. 15: Mooney PD, Sanders DS. Commentary: larazotide acetate - an exciting new development for coeliac patients? Aliment Pharmacol Ther. 2013 Feb;37(4):495-6. doi: 10.1111/apt.12183. PMID: 23336683. 16: Kelly CP, Green PH, Murray JA, Dimarino A, Colatrella A, Leffler DA, Alexander T, Arsenescu R, Leon F, Jiang JG, Arterburn LA, Paterson BM, Fedorak RN; Larazotide Acetate Celiac Disease Study Group. Larazotide acetate in patients with coeliac disease undergoing a gluten challenge: a randomised placebo-controlled study. Aliment Pharmacol Ther. 2013 Jan;37(2):252-62. doi: 10.1111/apt.12147. Epub 2012 Nov 19. PMID: 23163616. 17: Leffler DA, Kelly CP, Abdallah HZ, Colatrella AM, Harris LA, Leon F, Arterburn LA, Paterson BM, Lan ZH, Murray JA. A randomized, double-blind study of larazotide acetate to prevent the activation of celiac disease during gluten challenge. Am J Gastroenterol. 2012 Oct;107(10):1554-62. doi: 10.1038/ajg.2012.211. Epub 2012 Jul 24. PMID: 22825365; PMCID: PMC3463856. 18: Gopalakrishnan S, Tripathi A, Tamiz AP, Alkan SS, Pandey NB. Larazotide acetate promotes tight junction assembly in epithelial cells. Peptides. 2012 May;35(1):95-101. doi: 10.1016/j.peptides.2012.02.016. Epub 2012 Feb 28. PMID: 22401910. 19: Gopalakrishnan S, Durai M, Kitchens K, Tamiz AP, Somerville R, Ginski M, Paterson BM, Murray JA, Verdu EF, Alkan SS, Pandey NB. Larazotide acetate regulates epithelial tight junctions in vitro and in vivo. Peptides. 2012 May;35(1):86-94. doi: 10.1016/j.peptides.2012.02.015. Epub 2012 Feb 27. PMID: 22401908.