Teduglutide

Teduglutide
Clinical data
Trade names	Revestive, Gattex
AHFS/Drugs.com	Monograph
License data	US DailyMed: Teduglutide;
Routes of; administration	Subcutaneous injection
ATC code	A16AX08 (WHO) ;
Legal status
Legal status	AU: S4 (Prescription only); CA: ℞-only; US: ℞-only; EU: Rx-only;
Pharmacokinetic data
Bioavailability	88%
Metabolism	Proteolysis
Elimination half-life	2h
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;
UNII	7M19191IKG;
KEGG	D06053 ;
ChEBI	CHEBI:72305 ;
Chemical and physical data
Formula	C164H252N44O55S
Molar mass	3752.13 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 ;
	(verify)

Teduglutide, sold under the brand names Revestive (EU) and Gattex (US), 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.^[7] It was approved in both the European Union^[5] and the United States in 2012.^[4]

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.^[8]

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%).^[8]

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.^[8]

Society and culture

Legal status

It was approved in both the European Union (brand name Revestive)^[5]^[6] and the United States (brand name Gattex) in 2012.^[4] It was granted orphan drug designation by the European Medicines Agency (EMA).^[5]^[6]

References

^ "Prescription medicines: registration of new chemical entities in Australia, 2017". Therapeutic Goods Administration (TGA). 21 June 2022. Retrieved 9 April 2023.
^ "Prescription medicines and biologicals: TGA annual summary 2017". Therapeutic Goods Administration (TGA). 21 June 2022. Retrieved 31 March 2024.
^ "Health Canada New Drug Authorizations: 2015 Highlights". Health Canada. 4 May 2016. Retrieved 7 April 2024.
^ ^a ^b ^c "Gattex- teduglutide injection, powder, lyophilized, for solution; Gattex- teduglutide kit". DailyMed. 28 February 2024. Retrieved 20 March 2024.
^ ^a ^b ^c ^d "Revestive EPAR". European Medicines Agency (EMA). 11 December 2001. Retrieved 20 March 2024.
^ ^a ^b ^c "Revestive Product information". Union Register of medicinal products. 4 September 2012. Retrieved 20 March 2024.
^ Jeppesen PB (May 2012). "Teduglutide, a novel glucagon-like peptide 2 analog, in the treatment of patients with short bowel syndrome". Therapeutic Advances in Gastroenterology. 5 (3): 159–71. doi:10.1177/1756283X11436318. PMC 3342570. PMID 22570676.
^ ^a ^b ^c Klement A (5 January 2015). "Das Kurzdarmsyndrom ist erstmals behandelbar: Revestive". Österreichische Apothekerzeitung (in German) (1/2015): 20f.

[1] "Prescription medicines: registration of new chemical entities in Australia, 2017". Therapeutic Goods Administration (TGA). 21 June 2022. Retrieved 9 April 2023.

[2] "Prescription medicines and biologicals: TGA annual summary 2017". Therapeutic Goods Administration (TGA). 21 June 2022. Retrieved 31 March 2024.

[3] "Health Canada New Drug Authorizations: 2015 Highlights". Health Canada. 4 May 2016. Retrieved 7 April 2024.

[Gattex_FDA_label-4] "Gattex- teduglutide injection, powder, lyophilized, for solution; Gattex- teduglutide kit". DailyMed. 28 February 2024. Retrieved 20 March 2024.

[Revestive_EPAR-5] "Revestive EPAR". European Medicines Agency (EMA). 11 December 2001. Retrieved 20 March 2024.

[Revestive_EU_PI-6] "Revestive Product information". Union Register of medicinal products. 4 September 2012. Retrieved 20 March 2024.

[pmid22570676-7] Jeppesen PB (May 2012). "Teduglutide, a novel glucagon-like peptide 2 analog, in the treatment of patients with short bowel syndrome". Therapeutic Advances in Gastroenterology. 5 (3): 159–71. doi:10.1177/1756283X11436318. PMC 3342570. PMID 22570676.

[Klement-8] Klement A (5 January 2015). "Das Kurzdarmsyndrom ist erstmals behandelbar: Revestive". Österreichische Apothekerzeitung (in German) (1/2015): 20f.

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