Teduglutide

Teduglutide
Clinical data
Trade names	Gattex, Revestive
AHFS/Drugs.com	gattex
License data	EU EMA: by INN;
Pregnancy; category	US: B (No risk in non-human studies) ;
Routes of; administration	Subcutaneous injection
ATC code	A16AX08 (WHO) ;
Legal status
Legal status	US: ℞-only ;
Pharmacokinetic data
Bioavailability	88%
Metabolism	Proteolysis
Elimination half-life	2 h
Identifiers
	IUPAC name L-histidylglycyl-L-α-aspartylglycyl-L-seryl-L-phenylalanyl-L-seryl-L-α-aspartyl-L-α-glutamyl-L-methionyl-L-asparaginyl-L-threonyl-L-isoleucyl-L-leucyl-L-α-aspartyl-L-asparaginyl-L-leucyl-L-alanyl-L-alanyl-L-arginyl-L-α-aspartyl-L-phenylalanyl-L-isoleucyl-L-asparaginyl-L-tryptophyl-L-leucyl-L-isoleucyl-L-glutaminyl-L-threonyl-L-lysyl-L-isoleucyl-L-threonyl-L-aspartic acid;
CAS Number	197922-42-2;
PubChem CID	16139605;
IUPHAR/BPS	7049;
ChemSpider	17296109;
KEGG	D06053 ;
ChEBI	CHEBI:72305 ;
Chemical and physical data
Formula	C164H252N44O55S
Molar mass	3752.082 g/mol g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CC[C@H](C)[C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)Cc1cnc[nH]1)[C@@H](C)O)[C@@H](C)CC)[C@@H](C)CC)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(O)=O)C(O)=O;
	InChI InChI=1S/C164H252N44O55S/c1-21-77(11)126(156(255)187-95(44-46-114(167)214)141(240)206-130(83(17)211)160(259)186-93(42-33-34-49-165)140(239)202-129(80(14)24-4)159(258)208-131(84(18)212)161(260)200-111(163(262)263)66-125(230)231)203-151(250)100(54-76(9)10)189-145(244)103(57-88-67-175-92-41-32-31-40-90(88)92)192-147(246)105(60-116(169)216)199-157(256)127(78(12)22-2)204-152(251)102(56-87-38-29-26-30-39-87)190-149(248)109(64-123(226)227)195-137(236)94(43-35-50-174-164(171)172)183-134(233)82(16)179-133(232)81(15)180-142(241)98(52-74(5)6)188-146(245)104(59-115(168)215)194-150(249)110(65-124(228)229)196-143(242)99(53-75(7)8)198-158(257)128(79(13)23-3)205-162(261)132(85(19)213)207-153(252)106(61-117(170)217)193-139(238)97(48-51-264-20)185-138(237)96(45-47-120(220)221)184-148(247)108(63-122(224)225)197-155(254)113(72-210)201-144(243)101(55-86-36-27-25-28-37-86)191-154(253)112(71-209)182-119(219)70-177-136(235)107(62-121(222)223)181-118(218)69-176-135(234)91(166)58-89-68-173-73-178-89/h25-32,36-41,67-68,73-85,91,93-113,126-132,175,209-213H,21-24,33-35,42-66,69-72,165-166H2,1-20H3,(H2,167,214)(H2,168,215)(H2,169,216)(H2,170,217)(H,173,178)(H,176,234)(H,177,235)(H,179,232)(H,180,241)(H,181,218)(H,182,219)(H,183,233)(H,184,247)(H,185,237)(H,186,259)(H,187,255)(H,188,245)(H,189,244)(H,190,248)(H,191,253)(H,192,246)(H,193,238)(H,194,249)(H,195,236)(H,196,242)(H,197,254)(H,198,257)(H,199,256)(H,200,260)(H,201,243)(H,202,239)(H,203,250)(H,204,251)(H,205,261)(H,206,240)(H,207,252)(H,208,258)(H,220,221)(H,222,223)(H,224,225)(H,226,227)(H,228,229)(H,230,231)(H,262,263)(H4,171,172,174)/t77-,78-,79-,80-,81-,82-,83+,84+,85+,91-,93-,94-,95-,96-,97-,98-,99-,100-,101-,102-,103-,104-,105-,106-,107-,108-,109-,110-,111-,112-,113-,126-,127-,128-,129-,130-,131-,132-/m0/s1 ; Key:CILIXQOJUNDIDU-ASQIGDHWSA-N ;
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Teduglutide (brand names Gattex in the US and Revestive in Europe) is a 33-membered polypeptide and glucagon-like peptide-2 (GLP-2) analog that is used for the treatment of short bowel syndrome. It works by promoting mucosal growth and possibly restoring gastric emptying and secretion.[1] In Europe it has been granted orphan drug status and is marketed under the brand Revestive by Nycomed. It was approved by the United States under the name Gattex on 21 December 2012 and also is an orphan drug there.

Medical uses

Up to a certain point, the gut can adapt to partial resections that result in short bowel syndrome. Still, parenteral substitution of water, minerals and vitamins (depending on which part of the gut has been removed) is often necessary. Teduglutide may reduce or shorten the necessity of such infusions by improving the intestinal mucosa and possibly by other mechanisms.[2]

Adverse effects

Common adverse effects in clinical studies included abdominal discomfort (49% of patients), respiratory infections (28%), nausea (27%) and vomiting (14%), local reactions at the injection site (21%), and headache (17%).[2]

Chemistry and mechanism of action

Teduglutide differs from natural GLP-2 by a single amino acid: an alanine is replaced with a glycine. This blocks breaking down of the molecule by dipeptidyl peptidase and increases its half-life from seven minutes (GLP-2) to about two hours, while retaining its biological actions. These include maintenance of the intestinal mucosa, increasing intestinal blood flow, reducing gastrointestinal motility and secretion of gastric acid.[2]

References

Jeppesen PB (May 2012). "Teduglutide, a novel glucagon-like peptide 2 analog, in the treatment of patients with short bowel syndrome". Therap Adv Gastroenterol. 5 (3): 159–71. doi:10.1177/1756283X11436318. PMC 3342570. PMID 22570676.
A. Klement (5 January 2015). "Das Kurzdarmsyndrom ist erstmals behandelbar: Revestive". Österreichische Apothekerzeitung (in German) (1/2015): 20f.

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[pmid22570676-1] Jeppesen PB (May 2012). "Teduglutide, a novel glucagon-like peptide 2 analog, in the treatment of patients with short bowel syndrome". Therap Adv Gastroenterol. 5 (3): 159–71. doi:10.1177/1756283X11436318. PMC 3342570. PMID 22570676.

[Klement-2] A. Klement (5 January 2015). "Das Kurzdarmsyndrom ist erstmals behandelbar: Revestive". Österreichische Apothekerzeitung (in German) (1/2015): 20f.

Other alimentary tract and metabolism products (A16)
Amino acids and derivatives	Ademetionine Betaine Carglumic acid Cysteamine Levocarnitine Levoglutamide Metreleptin
Enzymes	Carbohydrate metabolism: sucrase (Sacrosidase) alpha-glucosidase (Alglucosidase alfa) Glycolipid/sphingolipid: glucocerebrosidase (Alglucerase Imiglucerase Taliglucerase alfa Velaglucerase alfa) alpha-galactosidase (Agalsidase alfa Agalsidase beta) Glycosaminoglycan: iduronidase (Laronidase) arylsulfatase B (Galsulfase) iduronate-2-sulfatase (Idursulfase) Lipid: lysosomal lipase (Sebelipase alfa) Phosphate: Asfotase alfa
Other	Anethole trithione Eliglustat Glycerol phenylbutyrate Miglustat Nitisinone Sapropterin Sodium benzoate Sodium phenylbutyrate Teduglutide Trientine Tioctic acid Uridine triacetate Zinc acetate