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 Aventis2016-07-27Not 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 Aventis2016-07-27Not applicableUs
AdlyxinLixisenatide (50 ug/1mL) + Lixisenatide (100 ug/1mL)KitSanofi Aventis2016-07-27Not 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
AcenocoumarolLixisenatide can cause a decrease in the absorption of Acenocoumarol resulting in a reduced serum concentration and potentially a decrease in efficacy.
AcetaminophenAcetaminophen may decrease the excretion rate of Lixisenatide which could result in a higher serum level.
AcetohexamideLixisenatide may increase the hypoglycemic activities of Acetohexamide.
Acetylsalicylic acidAcetylsalicylic acid may increase the hypoglycemic activities of Lixisenatide.
AlprazolamAlprazolam may decrease the excretion rate of Lixisenatide which could result in a higher serum level.
AmcinonideThe therapeutic efficacy of Lixisenatide can be decreased when used in combination with Amcinonide.
AmilorideAmiloride may increase the excretion rate of Lixisenatide which could result in a lower serum level and potentially a reduction in efficacy.
Aminosalicylic AcidAminosalicylic Acid may increase the hypoglycemic activities of Lixisenatide.
AmitriptylineLixisenatide may decrease the excretion rate of Amitriptyline which could result in a higher serum level.
AmlodipineAmlodipine may decrease the excretion rate of Lixisenatide which could result in a higher serum level.
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 Mellitus20
3RecruitingTreatmentType 2 Diabetes Mellitus3
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)
US9011391No2004-03-262024-03-26Us
US9233211No2004-03-022024-03-02Us
US8603044No2004-03-022024-03-02Us
US8512297No2004-09-152024-09-15Us
US8679069No2005-04-122025-04-12Us
US8992486No2004-06-052024-06-05Us
US8556864No2004-03-032024-03-03Us
US7918833Yes2008-03-232028-03-23Us
US9561331No2004-08-282024-08-28Us
US9623189No2004-08-192024-08-19Us
US9610409No2004-03-022024-03-02Us
US9526844No2004-03-022024-03-02Us
US9604008No2004-03-022024-03-02Us
US9533105No2004-08-172024-08-17Us
US9408979No2004-03-022024-03-02Us
US9604009No2004-08-162024-08-16Us
US9072836No2012-03-152032-03-15Us
US9084853No2011-10-052031-10-05Us
US8882721No2011-06-282031-06-28Us
US9511193No2012-01-192032-01-19Us
USRE45313No2000-07-122020-07-12Us
US8475414No2010-12-282030-12-28Us
US9308329No2010-12-282030-12-28Us
US8915888No2010-06-082030-06-08Us
US9408893No2012-08-272032-08-27Us
US9526764No2009-10-092029-10-09Us
US9707176No2010-11-112030-11-11Us
US9775954No2004-03-022024-03-02Us
US9827379No2004-03-022024-03-02Us
US9821032No2012-05-092032-05-09Us
US9855388No2009-04-242029-04-24Us
US9440029No2012-01-302032-01-30Us
US9950039No2015-12-102035-12-10Us
US9981013No2010-08-302030-08-30Us
US9717852No2013-04-082033-04-08Us
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 September 21, 2018 00:17