Identification

Name
Lixisenatide
Accession Number
DB09265
Type
Small Molecule
Groups
Approved
Description

Lixisenatide is a glucagon-like peptide-1 (GLP-1) receptor agonist used in the treatment of type 2 diabetes mellitus (T2DM). It is sold under the brand name Adlyxin by Sanofi-Aventis. Adlyxin recieved FDA approval July 28, 2016 [3].

Structure
Thumb
Synonyms
  • des-38-proline-exendine-4 (Heloderma suspectum)-(1-39)-peptidylpenta-L-lysyl-L-lysinamide
  • DesPro38Exendin-4(1-39)-Lys6-NH2
  • L-histidylglycyl-L-α-glutamylglycyl-L-threonyl-L-phenylalanyl-L-threonyl-L-seryl-L-α-aspartyl-L-leucyl-L-seryl-L-lysyl-L-glutaminyl-L-methionyl-L-α-glutamyl-L-α-glutamyl-L-α-glutamyl-L-alanyl-L-valyl-L-arginyl-L-leucyl-L-phenylalanyl-L-isoleucyl-L-α-glutamyl-L-tryptophyl-L-leucyl-L-lysyl-L-asparaginylglycylglycyl-L-prolyl-L-seryl-L-serylglycyl-L-alanyl-L-prolyl-L-prolyl-L-seryl-L-lysyl-L-lysyl-L-lysyl-L-lysyl-L-lysyl-L-lysinamide
  • lixisenatida
  • lixisénatide
External IDs
AQVE-10010 / AVE 0010 / AVE0010 / ZP 10 / ZP10A peptide
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
AdlyxinInjection, solution100 ug/1mLSubcutaneoussanofi-aventis U.S. LLC2016-07-27Not applicableUs
AdlyxineSolution0.1 mgSubcutaneousSanofi Aventis2017-09-12Not applicableCanada
AdlyxineSolution0.05 mgSubcutaneousSanofi Aventis2017-09-12Not applicableCanada
LyxumiaInjection, solution20 μgSubcutaneousSanofi Aventis Groupe2013-02-01Not applicableEu
LyxumiaInjection, solution10 μgSubcutaneousSanofi Aventis Groupe2013-02-01Not applicableEu
LyxumiaInjection, solution20 μgSubcutaneousSanofi Aventis Groupe2013-02-01Not applicableEu
LyxumiaInjection, solution20 μgSubcutaneousSanofi Aventis Groupe2013-02-01Not applicableEu
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
AdlyxinLixisenatide (50 ug/1mL) + Lixisenatide (100 ug/1mL)Kitsanofi-aventis U.S. LLC2016-07-27Not applicableUs
AdlyxinLixisenatide (50 ug/1mL) + Lixisenatide (100 ug/1mL)Kitsanofi-aventis U.S. LLC2016-07-27Not applicableUs
AdlyxineLixisenatide (0.05 mg) + Lixisenatide (0.1 mg)Kit; SolutionSubcutaneousSanofi Aventis2017-09-12Not applicableCanada
AdlyxineLixisenatide (0.05 mg) + Lixisenatide (0.1 mg)Kit; SolutionSubcutaneousSanofi Aventis2017-09-12Not applicableCanada
Soliqua 100/33Lixisenatide (33 ug/1mL) + Insulin Glargine (100 U/1mL)Injection, solutionSubcutaneousSanofi Aventis2016-11-21Not applicableUs
International/Other Brands
Lyxumia
Categories
UNII
74O62BB01U
CAS number
320367-13-3
Weight
Average: 4909.5
Monoisotopic: 4906.488279
Chemical Formula
C215H347N61O65SV
InChI Key
FIEORIYJJYKFHN-UDBQHKEXSA-N
InChI
InChI=1S/C215H347N61O65S.V/c1-16-115(10)173(210(337)256-141(68-74-170(299)300)194(321)261-148(94-122-98-232-126-50-24-23-49-124(122)126)199(326)258-143(89-111(2)3)196(323)247-134(58-32-40-83-223)189(316)262-149(96-160(226)285)180(307)235-100-161(286)233-104-165(290)274-85-42-60-156(274)207(334)267-154(108-280)206(333)265-151(105-277)181(308)237-101-162(287)239-117(12)213(340)276-87-44-62-158(276)214(341)275-86-43-61-157(275)208(335)268-153(107-279)204(331)249-132(56-30-38-81-221)187(314)246-131(55-29-37-80-220)186(313)245-130(54-28-36-79-219)185(312)244-129(53-27-35-78-218)184(311)243-128(52-26-34-77-217)183(310)242-127(176(227)303)51-25-33-76-216)272-201(328)146(92-120-45-19-17-20-46-120)260-197(324)144(90-112(4)5)257-190(317)135(59-41-84-231-215(228)229)255-209(336)172(114(8)9)271-177(304)116(11)240-182(309)138(65-71-167(293)294)251-192(319)139(66-72-168(295)296)252-193(320)140(67-73-169(297)298)253-195(322)142(75-88-342-15)254-191(318)137(63-69-159(225)284)250-188(315)133(57-31-39-82-222)248-203(330)152(106-278)266-198(325)145(91-113(6)7)259-200(327)150(97-171(301)302)263-205(332)155(109-281)269-212(339)175(119(14)283)273-202(329)147(93-121-47-21-18-22-48-121)264-211(338)174(118(13)282)270-164(289)103-236-179(306)136(64-70-166(291)292)241-163(288)102-234-178(305)125(224)95-123-99-230-110-238-123;/h17-24,45-50,98-99,110-119,125,127-158,172-175,232,277-283H,16,25-44,51-97,100-109,216-224H2,1-15H3,(H2,225,284)(H2,226,285)(H2,227,303)(H,230,238)(H,233,286)(H,234,305)(H,235,307)(H,236,306)(H,237,308)(H,239,287)(H,240,309)(H,241,288)(H,242,310)(H,243,311)(H,244,312)(H,245,313)(H,246,314)(H,247,323)(H,248,330)(H,249,331)(H,250,315)(H,251,319)(H,252,320)(H,253,322)(H,254,318)(H,255,336)(H,256,337)(H,257,317)(H,258,326)(H,259,327)(H,260,324)(H,261,321)(H,262,316)(H,263,332)(H,264,338)(H,265,333)(H,266,325)(H,267,334)(H,268,335)(H,269,339)(H,270,289)(H,271,304)(H,272,328)(H,273,329)(H,291,292)(H,293,294)(H,295,296)(H,297,298)(H,299,300)(H,301,302)(H4,228,229,231);/t115-,116-,117-,118+,119+,125-,127-,128-,129-,130-,131-,132-,133-,134-,135-,136-,137-,138-,139-,140-,141-,142-,143-,144-,145-,146-,147-,148-,149-,150-,151-,152-,153-,154-,155-,156-,157-,158-,172-,173-,174-,175-;/m0./s1
IUPAC Name
(4S)-4-{[(1S)-1-{[(1S)-1-{[(1S)-1-{[(1S)-1-{[(1S)-1-{[(1S)-1-{[(1S)-1-{[(1S,2S)-1-{[(1S)-1-{[(1S)-1-{[(1S)-1-{[(1S)-5-amino-1-{[(1S)-1-{[({2-[(2S)-2-{[(1S)-1-{[(1S)-1-[({[(2S)-1-[(2S)-2-[(2S)-2-{[(1S)-1-{[(1S)-5-amino-1-{[(1S)-5-amino-1-{[(1S)-5-amino-1-{[(1S)-5-amino-1-{[(1S)-5-amino-1-{[(1S)-5-amino-1-(C-hydroxycarbonimidoyl)pentyl]-C-hydroxycarbonimidoyl}pentyl]-C-hydroxycarbonimidoyl}pentyl]-C-hydroxycarbonimidoyl}pentyl]-C-hydroxycarbonimidoyl}pentyl]-C-hydroxycarbonimidoyl}pentyl]-C-hydroxycarbonimidoyl}-2-hydroxyethyl]-C-hydroxycarbonimidoyl}pyrrolidine-1-carbonyl]pyrrolidin-1-yl]-1-oxopropan-2-yl]-C-hydroxycarbonimidoyl}methyl)-C-hydroxycarbonimidoyl]-2-hydroxyethyl]-C-hydroxycarbonimidoyl}-2-hydroxyethyl]-C-hydroxycarbonimidoyl}pyrrolidin-1-yl]-2-oxoethyl}-C-hydroxycarbonimidoyl)methyl]-C-hydroxycarbonimidoyl}-2-(C-hydroxycarbonimidoyl)ethyl]-C-hydroxycarbonimidoyl}pentyl]-C-hydroxycarbonimidoyl}-3-methylbutyl]-C-hydroxycarbonimidoyl}-2-(1H-indol-3-yl)ethyl]-C-hydroxycarbonimidoyl}-3-carboxypropyl]-C-hydroxycarbonimidoyl}-2-methylbutyl]-C-hydroxycarbonimidoyl}-2-phenylethyl]-C-hydroxycarbonimidoyl}-3-methylbutyl]-C-hydroxycarbonimidoyl}-4-carbamimidamidobutyl]-C-hydroxycarbonimidoyl}-2-methylpropyl]-C-hydroxycarbonimidoyl}ethyl]-C-hydroxycarbonimidoyl}-3-carboxypropyl]-C-hydroxycarbonimidoyl}-3-carboxypropyl]-C-hydroxycarbonimidoyl}-4-{[(2S)-2-{[(2S)-2-{[(2S)-6-amino-2-{[(2S)-2-{[(2S)-2-{[(2S)-2-{[(2S)-2-{[(2S,3R)-2-{[(2S)-2-{[(2S,3R)-2-[(2-{[(2S)-2-[(2-{[(2S)-2-amino-1-hydroxy-3-(1H-imidazol-5-yl)propylidene]amino}-1-hydroxyethylidene)amino]-4-carboxy-1-hydroxybutylidene]amino}-1-hydroxyethylidene)amino]-1,3-dihydroxybutylidene]amino}-1-hydroxy-3-phenylpropylidene]amino}-1,3-dihydroxybutylidene]amino}-1,3-dihydroxypropylidene]amino}-3-carboxy-1-hydroxypropylidene]amino}-1-hydroxy-4-methylpentylidene]amino}-1,3-dihydroxypropylidene]amino}-1-hydroxyhexylidene]amino}-1-hydroxy-4-(C-hydroxycarbonimidoyl)butylidene]amino}-1-hydroxy-4-(methylsulfanyl)butylidene]amino}butanoic acid vanadium
SMILES
[V].[H][C@](C)(O)[C@]([H])(N=C(O)CN=C(O)[C@]([H])(CCC(O)=O)N=C(O)CN=C(O)[C@@]([H])(N)CC1=CN=CN1)C(O)=N[C@@]([H])(CC1=CC=CC=C1)C(O)=N[C@]([H])(C(O)=N[C@@]([H])(CO)C(O)=N[C@@]([H])(CC(O)=O)C(O)=N[C@@]([H])(CC(C)C)C(O)=N[C@@]([H])(CO)C(O)=N[C@@]([H])(CCCCN)C(O)=N[C@@]([H])(CCC(O)=N)C(O)=N[C@@]([H])(CCSC)C(O)=N[C@@]([H])(CCC(O)=O)C(O)=N[C@@]([H])(CCC(O)=O)C(O)=N[C@@]([H])(CCC(O)=O)C(O)=N[C@@]([H])(C)C(O)=N[C@@]([H])(C(C)C)C(O)=N[C@@]([H])(CCCNC(N)=N)C(O)=N[C@@]([H])(CC(C)C)C(O)=N[C@@]([H])(CC1=CC=CC=C1)C(O)=N[C@]([H])(C(O)=N[C@@]([H])(CCC(O)=O)C(O)=N[C@@]([H])(CC1=CNC2=CC=CC=C12)C(O)=N[C@@]([H])(CC(C)C)C(O)=N[C@@]([H])(CCCCN)C(O)=N[C@@]([H])(CC(O)=N)C(O)=NCC(O)=NCC(=O)N1CCC[C@@]1([H])C(O)=N[C@@]([H])(CO)C(O)=N[C@@]([H])(CO)C(O)=NCC(O)=N[C@@]([H])(C)C(=O)N1CCC[C@@]1([H])C(=O)N1CCC[C@@]1([H])C(O)=N[C@@]([H])(CO)C(O)=N[C@@]([H])(CCCCN)C(O)=N[C@@]([H])(CCCCN)C(O)=N[C@@]([H])(CCCCN)C(O)=N[C@@]([H])(CCCCN)C(O)=N[C@@]([H])(CCCCN)C(O)=N[C@@]([H])(CCCCN)C(O)=N)[C@@]([H])(C)CC)[C@@]([H])(C)O

Pharmacology

Indication

For use as an antihyperglycemic agent in the treatment of T2DM [Label].

Associated Conditions
Pharmacodynamics

Lixisenatide acts as an agonist at the GLP-1 receptor. In the pancreas, this agonism results in increased glucose-stimulated insulin exocytosis by beta islet cells. This produces a reduction in blood glucose due to increased glucose uptake by tissues [1]. GLP-1 receptor activation in the GI tract results in delayed gastric emptying which is thought to mediate the effects of lixisenatide on postprandial blood glucose.

Mechanism of action

The activation of the GLP-1 receptor by lixisenatide results in the activation of adenylyl cyclase [19193]. This increases the concentration of cyclic adenosine monophosphate in the cell leading to the activation of protein kinase A (PKA) as well as Epac1 and Epac2. PKA, Epac1, and Epac2 are involved the in release of Ca2+ from the endoplasmic reticulum which is known as the "amplification" pathway which increases insulin release when the triggering pathway is activated. By activating this amplification pathway lixisenatide increases glucose stimulated insulin secretion.

TargetActionsOrganism
AGlucagon-like peptide 1 receptor
agonist
Human
Absorption

tmax of 1-3.5h when administered subcutaneously [Label].

Volume of distribution

100L [Label]

Protein binding

55% bound to plasma proteins [4].

Metabolism

Assumed to undergo proteolytic degradation [Label].

Route of elimination

Assumed to be proteolytic degradation and excretion in urine [Label].

Half life

3h [Label]

Clearance

35L/h [Label]

Toxicity

Thyroid C-cell adenomas occurred in rats when exposed to >15 times human exposure of 20mcg/day [Label]. Overdose is associated with GI side effects typical of GLP-1 receptor agonists.

Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinLixisenatide can cause a decrease in the absorption of (R)-warfarin resulting in a reduced serum concentration and potentially a decrease in efficacy.
(S)-WarfarinLixisenatide can cause a decrease in the absorption of (S)-Warfarin resulting in a reduced serum concentration and potentially a decrease in efficacy.
2,4-thiazolidinedioneThe risk or severity of hypoglycemia can be increased when Lixisenatide is combined with 2,4-thiazolidinedione.
4-hydroxycoumarinLixisenatide can cause a decrease in the absorption of 4-hydroxycoumarin resulting in a reduced serum concentration and potentially a decrease in efficacy.
5-(2-methylpiperazine-1-sulfonyl)isoquinolineThe therapeutic efficacy of Lixisenatide can be increased when used in combination with 5-(2-methylpiperazine-1-sulfonyl)isoquinoline.
AbacavirAbacavir may decrease the excretion rate of Lixisenatide which could result in a higher serum level.
AcarboseThe risk or severity of hypoglycemia can be increased when Acarbose is combined with Lixisenatide.
AceclofenacAceclofenac may decrease the excretion rate of Lixisenatide which could result in a higher serum level.
AcemetacinAcemetacin may decrease the excretion rate of Lixisenatide which could result in a higher serum level.
AcenocoumarolLixisenatide can cause a decrease in the absorption of Acenocoumarol resulting in a reduced serum concentration and potentially a decrease in efficacy.
Food Interactions
Not Available

References

General References
  1. Lorenz M, Pfeiffer C, Steinstrasser A, Becker RH, Rutten H, Ruus P, Horowitz M: Effects of lixisenatide once daily on gastric emptying in type 2 diabetes--relationship to postprandial glycemia. Regul Pept. 2013 Aug 10;185:1-8. doi: 10.1016/j.regpep.2013.04.001. Epub 2013 May 9. [PubMed:23665027]
  2. Doyle ME, Egan JM: Mechanisms of action of glucagon-like peptide 1 in the pancreas. Pharmacol Ther. 2007 Mar;113(3):546-93. Epub 2006 Dec 28. [PubMed:17306374]
  3. Adlyxin FDA Approval Announcement [Link]
  4. EMA Lixisenatide Assessment [Link]
External Links
PubChem Compound
131704317
PubChem Substance
310265161
ChemSpider
64873334
ChEBI
85662
ChEMBL
CHEMBL2108336
Wikipedia
Lixisenatide
ATC Codes
A10BX10 — Lixisenatide
AHFS Codes
  • 68:20.06 — Incretin Mimetics
FDA label
Download (1.13 MB)
MSDS
Download (80 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentType 2 Diabetes Mellitus2
1RecruitingTreatmentType 2 Diabetes Mellitus1
1TerminatedTreatmentDiabetes Mellitus (DM)1
1, 2RecruitingTreatmentDiabetes Mellitus (DM) / Gastroparesis1
2CompletedTreatmentType 2 Diabetes Mellitus3
2RecruitingTreatmentParkinson's Disease (PD)1
3Active Not RecruitingTreatmentType 2 Diabetes Mellitus3
3CompletedTreatmentAcute Coronary Syndromes (ACS)1
3CompletedTreatmentType 2 Diabetes Mellitus21
3RecruitingTreatmentType 2 Diabetes Mellitus2
4Active Not RecruitingTreatmentType 2 Diabetes Mellitus1
4CompletedBasic ScienceType 2 Diabetes Mellitus1
4CompletedTreatmentDiabetes Mellitus (DM) / Diabetic Kidney Disease / Diabetic Nephropathies / Glucagon-Like Peptide 11
4CompletedTreatmentDiabetes Mellitus (DM) / Type 2 Diabetes Mellitus1
4RecruitingTreatmentType 2 Diabetes Mellitus1
4TerminatedTreatmentType 2 Diabetes Mellitus1
Not AvailableCompletedBasic ScienceDiabetes After Total Pancreatectomy1
Not AvailableCompletedBasic ScienceDiabetes Mellitus (DM)1
Not AvailableRecruitingPreventionIncretinomimetics / Pancreas / Type 2 Diabetes Mellitus1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Injection, solutionSubcutaneous100 ug/1mL
Kit
Kit; solutionSubcutaneous
SolutionSubcutaneous0.05 mg
SolutionSubcutaneous0.1 mg
Injection, solutionSubcutaneous10 μg
Injection, solutionSubcutaneous20 μg
Injection, solutionSubcutaneous
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US9011391No2015-04-212024-03-26Us
US9233211No2016-01-122024-03-02Us
US8603044No2013-12-102024-03-02Us
US8512297No2013-08-202024-09-15Us
US8679069No2014-03-252025-04-12Us
US8992486No2015-03-312024-06-05Us
US8556864No2013-10-152024-03-03Us
US7918833Yes2011-04-052028-03-23Us
US9561331No2017-02-072024-08-28Us
US9623189No2017-04-182024-08-19Us
US9610409No2017-04-042024-03-02Us
US9526844No2016-12-272024-03-02Us
US9604008No2017-03-282024-03-02Us
US9533105No2017-01-032024-08-17Us
US9408979No2016-08-092024-03-02Us
US9604009No2017-03-282024-08-16Us
US9072836No2015-07-072032-03-15Us
US9084853No2015-07-212031-10-05Us
US8882721No2014-11-112031-06-28Us
US9511193No2016-12-062032-01-19Us
USRE45313No2014-12-302020-07-12Us
US8475414No2013-07-022030-12-28Us
US9308329No2016-04-122030-12-28Us
US8915888No2014-12-232030-06-08Us
US9408893No2016-08-092032-08-27Us
US9526764No2016-12-272029-10-09Us
US9707176No2017-07-182030-11-11Us
US9775954No2017-10-032024-03-02Us
US9827379No2017-11-282024-03-02Us
US9821032No2017-11-212032-05-09Us
US9855388No2018-01-022029-04-24Us
US9440029No2016-09-132032-01-30Us
US9950039No2018-04-242035-12-10Us
US9981013No2018-05-292030-08-30Us
US9717852No2017-08-012033-04-08Us
US10028910No2010-11-112030-11-11Us
US10029011No2012-08-022032-08-02Us

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
logP4.15ChemAxon
pKa (Strongest Acidic)2.41ChemAxon
pKa (Strongest Basic)11.86ChemAxon
Physiological Charge-6ChemAxon
Hydrogen Acceptor Count121ChemAxon
Hydrogen Donor Count73ChemAxon
Polar Surface Area2202.73 Å2ChemAxon
Rotatable Bond Count169ChemAxon
Refractivity1275.61 m3·mol-1ChemAxon
Polarizability508.51 Å3ChemAxon
Number of Rings8ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Taxonomy

Classification
Not classified

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
General Function
Transmembrane signaling receptor activity
Specific Function
This is a receptor for glucagon-like peptide 1. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase.
Gene Name
GLP1R
Uniprot ID
P43220
Uniprot Name
Glucagon-like peptide 1 receptor
Molecular Weight
53025.22 Da

Drug created on October 27, 2015 15:41 / Updated on November 18, 2018 13:32