Ferroptosis-centered Drug Response Information

General Information of the Drug (ID: ferrodrug0155)
Name
Liraglutide
Synonyms
Liraglutide; 204656-20-2; NN2211; victoza; Liraglutida; Liraglutidum; NN-2211; NN 2211; UNII-839I73S42A; HSDB 8205; Liraglutide (rDNA origin); NNC 90-1170; CHEMBL4084119; Saxenda; CHEBI:71193; DTXSID60174433; 839I73S42A; NN-9924; NNC-90-1170; N26-(Hexadecanoyl-gamma-glutamyle)-(34-arginine)GLP-1-(7-37)-peptide; N26-(Hexadecanoyl-gamma-glutamyle)-(34-arginine)glucagon-like-peptide-1-(7-37)-peptide; Arg34Lys26-(N-epsilon-(gamma-Glu(N-alpha-hexadecanoyl)))-GLP-1(7-37); Liraglutidum [INN-Latin]; N(sup 26)-(Hexadecanoyl-gamma-glutamyle)-(34-arginine)GLP-1-(7-37)-peptide; Liraglutida [INN-Spanish]; Liraglutide recombinant; Liraglutide [USAN:INN:BAN:JAN]; Liraglutidum (Latin); LIRAGLUTIDE (MART.); GTPL1133; DTXCID6096924; A10BJ02; EX-A2418; BDBM50240819; NN9924; AKOS037435224; AS-56276; A16115; XULTOPHY 100/3.6 COMPONENT LIRAGLUTIDE; LIRAGLUTIDE COMPONENT OF XULTOPHY 100/3.6; ARG(SUP 34)LYS(SUP 26)-(N-epsilon-(gamma-GLU(N-alpha-HEXADECANOYL)))-GLP-1(7-37); N(SUP epsilon26)-(N-HEXADECANOYL-L-gamma-GLUTAMYL)-(34-L-ARGININE)GLUCAGON-LIKE PEPTIDE 1-(7-37)-PEPTIDE; N26-(N-Hexadecanoyl-L-gamma-glutamyl)-(34-L-arginine)glucagon-like peptide 1-(7-37)-peptide

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Status
Approved
Drug Type
Small molecular drug
Structure
3D MOL
2D MOL
Formula
C172H265N43O51
IUPAC Name
(2S)-5-[[(5S)-5-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S,3R)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-3-(1H-imidazol-5-yl)propanoyl]amino]propanoyl]amino]-4-carboxybutanoyl]amino]acetyl]amino]-3-hydroxybutanoyl]amino]-3-phenylpropanoyl]amino]-3-hydroxybutanoyl]amino]-3-hydroxypropanoyl]amino]-3-carboxypropanoyl]amino]-3-methylbutanoyl]amino]-3-hydroxypropanoyl]amino]-3-hydroxypropanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-methylpentanoyl]amino]-4-carboxybutanoyl]amino]acetyl]amino]-5-oxopentanoyl]amino]propanoyl]amino]propanoyl]amino]-6-[[(2S)-1-[[(2S)-1-[[(2S,3S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-5-carbamimidamido-1-[[2-[[(2S)-5-carbamimidamido-1-(carboxymethylamino)-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-1-oxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-6-oxohexyl]amino]-2-(hexadecanoylamino)-5-oxopentanoic acid
Canonical SMILES
CCCCCCCCCCCCCCCC(=O)NC(CCC(=O)NCCCCC(C(=O)NC(CCC(=O)O)C(=O)NC(CC1=CC=CC=C1)C(=O)NC(C(C)CC)C(=O)NC(C)C(=O)NC(CC2=CNC3=CC=CC=C32)C(=O)NC(CC(C)C)C(=O)NC(C(C)C)C(=O)NC(CCCNC(=N)N)C(=O)NCC(=O)NC(CCCNC(=N)N)C(=O)NCC(=O)O)NC(=O)C(C)NC(=O)C(C)NC(=O)C(CCC(=O)N)NC(=O)CNC(=O)C(CCC(=O)O)NC(=O)C(CC(C)C)NC(=O)C(CC4=CC=C(C=C4)O)NC(=O)C(CO)NC(=O)C(CO)NC(=O)C(C(C)C)NC(=O)C(CC(=O)O)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C(CC5=CC=CC=C5)NC(=O)C(C(C)O)NC(=O)CNC(=O)C(CCC(=O)O)NC(=O)C(C)NC(=O)C(CC6=CN=CN6)N)C(=O)O
InChI
InChI=1S/C172H265N43O51/c1-18-20-21-22-23-24-25-26-27-28-29-30-37-53-129(224)195-116(170(265)266)59-64-128(223)180-68-41-40-50-111(153(248)199-115(62-67-135(232)233)154(249)204-120(73-100-44-33-31-34-45-100)159(254)214-140(93(11)19-2)167(262)192-97(15)146(241)201-122(76-103-79-183-108-49-39-38-48-106(103)108)157(252)203-118(72-90(5)6)158(253)212-138(91(7)8)165(260)200-110(52-43-70-182-172(177)178)149(244)184-81-130(225)193-109(51-42-69-181-171(175)176)148(243)187-84-137(236)237)196-144(239)95(13)189-143(238)94(12)191-152(247)114(58-63-127(174)222)194-131(226)82-185-151(246)113(61-66-134(230)231)198-155(250)117(71-89(3)4)202-156(251)119(75-102-54-56-105(221)57-55-102)205-162(257)124(85-216)208-164(259)126(87-218)209-166(261)139(92(9)10)213-161(256)123(78-136(234)235)206-163(258)125(86-217)210-169(264)142(99(17)220)215-160(255)121(74-101-46-35-32-36-47-101)207-168(263)141(98(16)219)211-132(227)83-186-150(245)112(60-65-133(228)229)197-145(240)96(14)190-147(242)107(173)77-104-80-179-88-188-104/h31-36,38-39,44-49,54-57,79-80,88-99,107,109-126,138-142,183,216-221H,18-30,37,40-43,50-53,58-78,81-87,173H2,1-17H3,(H2,174,222)(H,179,188)(H,180,223)(H,184,244)(H,185,246)(H,186,245)(H,187,243)(H,189,238)(H,190,242)(H,191,247)(H,192,262)(H,193,225)(H,194,226)(H,195,224)(H,196,239)(H,197,240)(H,198,250)(H,199,248)(H,200,260)(H,201,241)(H,202,251)(H,203,252)(H,204,249)(H,205,257)(H,206,258)(H,207,263)(H,208,259)(H,209,261)(H,210,264)(H,211,227)(H,212,253)(H,213,256)(H,214,254)(H,215,255)(H,228,229)(H,230,231)(H,232,233)(H,234,235)(H,236,237)(H,265,266)(H4,175,176,181)(H4,177,178,182)/t93-,94-,95-,96-,97-,98+,99+,107-,109-,110-,111-,112-,113-,114-,115-,116-,117-,118-,119-,120-,121-,122-,123-,124-,125-,126-,138-,139-,140-,141-,142-/m0/s1
InChIKey
YSDQQAXHVYUZIW-QCIJIYAXSA-N
PubChem CID
16134956
TTD Drug ID
D03GOI
Full List of Ferroptosis Target Related to This Drug
Long-chain-fatty-acid--CoA ligase 4 (ACSL4)
 Target Info 
In total 1 item(s) under this Target
Experiment 1 Reporting the Ferroptosis-centered Drug Act on This Target [1]
Target for Ferroptosis Driver
Responsed Disease Cognitive disorder ICD-11: 6D71
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model mHNs (Mouse hippocampal neurons)
In Vivo Model
Male diabetic db/db mice and nondiabetic littermate db/m mice that were 4 weeks of age were purchased from Changzhou Cavens Experimental Animal Co., Ltd. After 1week of adaptive feeding, 20 db/db mice were randomly divided into two groups: a model group (db/db, n = 10) and a treatment group (LIRA, n = 10). Another 10 db/m mice were used as the control group (db/m, n = 10). After feeding to 10weeks old, the LIRA group was given liraglutide (CSN11311, CSNpharm, China) diluent (200 ug/kg/d) by intraperitoneal injection for 5 weeks, with equivoluminal 0.9% saline intraperitoneally administered to the other two groups.

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Response regulation Liraglutide was shown to prevent ferroptosis in the hippocampus by elevating the expression of GPX4 and SLC7A11 and suppressing the excessive amount of ACSL4. LIRA can reduce oxidative stress, lipid peroxidation and iron overload in diabetes-induced cognitive dysfunction and further inhibit ferroptosis, thereby weakening the damage to hippocampal neurons and synaptic plasticity and ultimately restoring cognitive function.
Cystine/glutamate transporter (SLC7A11)
 Target Info 
In total 1 item(s) under this Target
Experiment 1 Reporting the Ferroptosis-centered Drug Act on This Target [1]
Target for Ferroptosis Suppressor
Responsed Disease Cognitive disorder ICD-11: 6D71
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model mHNs (Mouse hippocampal neurons)
In Vivo Model
Male diabetic db/db mice and nondiabetic littermate db/m mice that were 4 weeks of age were purchased from Changzhou Cavens Experimental Animal Co., Ltd. After 1week of adaptive feeding, 20 db/db mice were randomly divided into two groups: a model group (db/db, n = 10) and a treatment group (LIRA, n = 10). Another 10 db/m mice were used as the control group (db/m, n = 10). After feeding to 10weeks old, the LIRA group was given liraglutide (CSN11311, CSNpharm, China) diluent (200 ug/kg/d) by intraperitoneal injection for 5 weeks, with equivoluminal 0.9% saline intraperitoneally administered to the other two groups.

    Click to Show/Hide
Response regulation Liraglutide was shown to prevent ferroptosis in the hippocampus by elevating the expression of GPX4 and SLC7A11 and suppressing the excessive amount of ACSL4. LIRA can reduce oxidative stress, lipid peroxidation and iron overload in diabetes-induced cognitive dysfunction and further inhibit ferroptosis, thereby weakening the damage to hippocampal neurons and synaptic plasticity and ultimately restoring cognitive function.
References
Ref 1 Liraglutide Alleviates Cognitive Deficit in db/db Mice: Involvement in Oxidative Stress, Iron Overload, and Ferroptosis. Neurochem Res. 2022 Feb;47(2):279-294. doi: 10.1007/s11064-021-03442-7. Epub 2021 Sep 4.