Ularitide

Identification

Name
Ularitide
Accession Number
DB05034
Type
Small Molecule
Groups
Investigational
Description

Ularitide is a synthetic form of urodilatin, a naturally occurring human natriuretic peptide that is involved in regulating blood pressure and the excretion of water and sodium from the kidneys. Urodilatin is produced in the kidney and excreted into the urine, and thus exists in low levels naturally in the systemic blood circulation. When injected into the blood, ularitide appears to cause diuresis (urine output) and natriuresis (sodium excretion), as well as vasodilation. Ularitide is currently in Phase 2 development as a potential treatment for patients with acute decompensated heart failure (ADHF).

Structure
Thumb
Synonyms
  • Urodilatin ularitide
Categories
UNII
740Y5J48Z8
CAS number
118812-69-4
Weight
Average: 3505.926
Monoisotopic: 3503.683361186
Chemical Formula
C145H234N52O44S3
InChI Key
IUCCYQIEZNQWRS-DWWHXVEHSA-N
InChI
InChI=1S/C145H234N52O44S3/c1-11-72(6)112-137(238)171-60-106(208)172-73(7)113(214)177-86(40-41-103(146)205)122(223)190-95(63-198)116(217)170-61-108(210)175-88(51-70(2)3)114(215)169-62-109(211)176-100(133(234)187-92(56-104(147)206)127(228)193-97(65-200)130(231)186-91(54-77-27-16-13-17-28-77)126(227)180-82(31-20-45-163-142(153)154)119(220)189-94(139(240)241)55-78-36-38-79(204)39-37-78)68-243-244-69-101(134(235)185-90(53-76-25-14-12-15-26-76)115(216)168-58-105(207)167-59-107(209)174-80(29-18-43-161-140(149)150)117(218)182-87(42-50-242-10)123(224)188-93(57-110(212)213)128(229)181-85(124(225)196-112)34-23-48-166-145(159)160)195-132(233)99(67-202)194-131(232)98(66-201)192-120(221)83(32-21-46-164-143(155)156)178-118(219)81(30-19-44-162-141(151)152)179-125(226)89(52-71(4)5)184-129(230)96(64-199)191-121(222)84(33-22-47-165-144(157)158)183-135(236)102-35-24-49-197(102)138(239)74(8)173-136(237)111(148)75(9)203/h12-17,25-28,36-39,70-75,80-102,111-112,198-204H,11,18-24,29-35,40-69,148H2,1-10H3,(H2,146,205)(H2,147,206)(H,167,207)(H,168,216)(H,169,215)(H,170,217)(H,171,238)(H,172,208)(H,173,237)(H,174,209)(H,175,210)(H,176,211)(H,177,214)(H,178,219)(H,179,226)(H,180,227)(H,181,229)(H,182,218)(H,183,236)(H,184,230)(H,185,235)(H,186,231)(H,187,234)(H,188,224)(H,189,220)(H,190,223)(H,191,222)(H,192,221)(H,193,228)(H,194,232)(H,195,233)(H,196,225)(H,212,213)(H,240,241)(H4,149,150,161)(H4,151,152,162)(H4,153,154,163)(H4,155,156,164)(H4,157,158,165)(H4,159,160,166)/t72-,73-,74-,75+,80-,81-,82-,83-,84-,85-,86-,87-,88-,89-,90-,91-,92-,93-,94-,95-,96-,97-,98-,99-,100-,101-,102-,111-,112-/m0/s1
IUPAC Name
(2S)-2-[(2S)-2-[(2S)-2-[(2S)-2-[(2S)-2-{[(4R,10S,16S,19S,22S,28S,31S,34S,37S,40S,49S,52R)-52-[(2S)-2-[(2S)-2-[(2S)-2-[(2S)-2-[(2S)-2-[(2S)-2-[(2S)-2-{[(2S)-1-[(2S)-2-[(2S,3R)-2-amino-3-hydroxybutanamido]propanoyl]pyrrolidin-2-yl]formamido}-5-carbamimidamidopentanamido]-3-hydroxypropanamido]-4-methylpentanamido]-5-carbamimidamidopentanamido]-5-carbamimidamidopentanamido]-3-hydroxypropanamido]-3-hydroxypropanamido]-49-benzyl-28-[(2S)-butan-2-yl]-31,40-bis(3-carbamimidamidopropyl)-19-(2-carbamoylethyl)-34-(carboxymethyl)-16-(hydroxymethyl)-22-methyl-10-(2-methylpropyl)-37-[2-(methylsulfanyl)ethyl]-6,9,12,15,18,21,24,27,30,33,36,39,42,45,48,51-hexadecaoxo-1,2-dithia-5,8,11,14,17,20,23,26,29,32,35,38,41,44,47,50-hexadecaazacyclotripentacontan-4-yl]formamido}-3-carbamoylpropanamido]-3-hydroxypropanamido]-3-phenylpropanamido]-5-carbamimidamidopentanamido]-3-(4-hydroxyphenyl)propanoic acid
SMILES
CC[[email protected]](C)[[email protected]@H]1NC(=O)[[email protected]](CCCNC(N)=N)NC(=O)[[email protected]](CC(O)=O)NC(=O)[[email protected]](CCSC)NC(=O)[[email protected]](CCCNC(N)=N)NC(=O)CNC(=O)CNC(=O)[[email protected]](CC2=CC=CC=C2)NC(=O)[[email protected]](CSSC[[email protected]](NC(=O)CNC(=O)[[email protected]](CC(C)C)NC(=O)CNC(=O)[[email protected]](CO)NC(=O)[[email protected]](CCC(N)=O)NC(=O)[[email protected]](C)NC(=O)CNC1=O)C(=O)N[[email protected]@H](CC(N)=O)C(=O)N[[email protected]@H](CO)C(=O)N[[email protected]@H](CC1=CC=CC=C1)C(=O)N[[email protected]@H](CCCNC(N)=N)C(=O)N[[email protected]@H](CC1=CC=C(O)C=C1)C(O)=O)NC(=O)[[email protected]](CO)NC(=O)[[email protected]](CO)NC(=O)[[email protected]](CCCNC(N)=N)NC(=O)[[email protected]](CCCNC(N)=N)NC(=O)[[email protected]](CC(C)C)NC(=O)[[email protected]](CO)NC(=O)[[email protected]](CCCNC(N)=N)NC(=O)[[email protected]@H]1CCCN1C(=O)[[email protected]](C)NC(=O)[[email protected]@H](N)[[email protected]@H](C)O

Pharmacology

Indication

Investigated for use/treatment in congestive heart failure.

Structured Indications
Not Available
Pharmacodynamics
Not Available
Mechanism of action

Ularitide, a synthetic form of urodilatin, belongs to the family of natriuretic peptides. Urodilatin stimulates the intracellular guanylyl cyclase as the intracellular domain of the natriuretic peptide receptor A (NPR-A), the enzyme that catalyzes the conversion of GTP to cGMP [7]. Activation of cGMP-dependent protein kinase inhibits sodium reabsorption via an amiloride-sensitive channel and furthermore results in smooth muscle relaxation via a decrease in intracellular Ca2+ concentration. Thus, ularitide is an intrarenal paracrine regulator of sodium and water homeostasis.

TargetActionsOrganism
UAtrial natriuretic peptide receptor 1Not AvailableHuman
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AlfentanilThe risk or severity of adverse effects can be increased when Alfentanil is combined with Ularitide.Approved, Illicit
AlphacetylmethadolThe risk or severity of adverse effects can be increased when Alphacetylmethadol is combined with Ularitide.Experimental, Illicit
AlphaprodineThe risk or severity of adverse effects can be increased when Alphaprodine is combined with Ularitide.Illicit
BezitramideThe risk or severity of adverse effects can be increased when Bezitramide is combined with Ularitide.Experimental, Illicit, Withdrawn
BuprenorphineThe risk or severity of adverse effects can be increased when Buprenorphine is combined with Ularitide.Approved, Illicit, Investigational, Vet Approved
ButorphanolThe risk or severity of adverse effects can be increased when Butorphanol is combined with Ularitide.Approved, Illicit, Vet Approved
CarfentanilThe risk or severity of adverse effects can be increased when Carfentanil is combined with Ularitide.Illicit, Investigational, Vet Approved
CodeineThe risk or severity of adverse effects can be increased when Codeine is combined with Ularitide.Approved, Illicit
DextromoramideThe risk or severity of adverse effects can be increased when Dextromoramide is combined with Ularitide.Experimental, Illicit
DextropropoxypheneThe risk or severity of adverse effects can be increased when Dextropropoxyphene is combined with Ularitide.Approved, Illicit, Investigational, Withdrawn
DezocineThe risk or severity of adverse effects can be increased when Dezocine is combined with Ularitide.Approved, Investigational
DihydrocodeineThe risk or severity of adverse effects can be increased when Dihydrocodeine is combined with Ularitide.Approved, Illicit
DihydroetorphineThe risk or severity of adverse effects can be increased when Dihydroetorphine is combined with Ularitide.Experimental, Illicit
DihydromorphineThe risk or severity of adverse effects can be increased when Dihydromorphine is combined with Ularitide.Experimental, Illicit
DiphenoxylateThe risk or severity of adverse effects can be increased when Diphenoxylate is combined with Ularitide.Approved, Illicit
DPDPEThe risk or severity of adverse effects can be increased when DPDPE is combined with Ularitide.Experimental
EthylmorphineThe risk or severity of adverse effects can be increased when Ethylmorphine is combined with Ularitide.Approved, Illicit
EtorphineThe risk or severity of adverse effects can be increased when Etorphine is combined with Ularitide.Illicit, Vet Approved
FentanylThe risk or severity of adverse effects can be increased when Fentanyl is combined with Ularitide.Approved, Illicit, Investigational, Vet Approved
HeroinThe risk or severity of adverse effects can be increased when Heroin is combined with Ularitide.Approved, Illicit, Investigational
HydrocodoneThe risk or severity of adverse effects can be increased when Hydrocodone is combined with Ularitide.Approved, Illicit
HydromorphoneThe risk or severity of adverse effects can be increased when Hydromorphone is combined with Ularitide.Approved, Illicit
KetobemidoneThe risk or severity of adverse effects can be increased when Ketobemidone is combined with Ularitide.Approved, Investigational
Levomethadyl AcetateThe risk or severity of adverse effects can be increased when Levomethadyl Acetate is combined with Ularitide.Approved, Investigational
LevorphanolThe risk or severity of adverse effects can be increased when Levorphanol is combined with Ularitide.Approved
LofentanilThe risk or severity of adverse effects can be increased when Lofentanil is combined with Ularitide.Illicit
MeptazinolThe risk or severity of adverse effects can be increased when Meptazinol is combined with Ularitide.Experimental
MethadoneThe risk or severity of adverse effects can be increased when Methadone is combined with Ularitide.Approved
Methadyl AcetateThe risk or severity of adverse effects can be increased when Methadyl Acetate is combined with Ularitide.Approved, Illicit
MorphineThe risk or severity of adverse effects can be increased when Morphine is combined with Ularitide.Approved, Investigational
NalbuphineThe risk or severity of adverse effects can be increased when Nalbuphine is combined with Ularitide.Approved
NicomorphineThe risk or severity of adverse effects can be increased when Nicomorphine is combined with Ularitide.Experimental
NormethadoneThe risk or severity of adverse effects can be increased when Normethadone is combined with Ularitide.Approved, Illicit
OpiumThe risk or severity of adverse effects can be increased when Opium is combined with Ularitide.Approved, Illicit
OxycodoneThe risk or severity of adverse effects can be increased when Oxycodone is combined with Ularitide.Approved, Illicit, Investigational
OxymorphoneThe risk or severity of adverse effects can be increased when Oxymorphone is combined with Ularitide.Approved, Investigational, Vet Approved
PentazocineThe risk or severity of adverse effects can be increased when Pentazocine is combined with Ularitide.Approved, Vet Approved
PethidineThe risk or severity of adverse effects can be increased when Pethidine is combined with Ularitide.Approved
PhenazocineThe risk or severity of adverse effects can be increased when Phenazocine is combined with Ularitide.Experimental
PhenoperidineThe risk or severity of adverse effects can be increased when Phenoperidine is combined with Ularitide.Experimental
PiritramideThe risk or severity of adverse effects can be increased when Piritramide is combined with Ularitide.Investigational
RemifentanilThe risk or severity of adverse effects can be increased when Remifentanil is combined with Ularitide.Approved
Sodium phosphateUlaritide may increase the nephrotoxic activities of Sodium phosphate.Approved
SufentanilThe risk or severity of adverse effects can be increased when Sufentanil is combined with Ularitide.Approved, Investigational
TapentadolThe risk or severity of adverse effects can be increased when Tapentadol is combined with Ularitide.Approved
TilidineThe risk or severity of adverse effects can be increased when Tilidine is combined with Ularitide.Experimental
TramadolThe risk or severity of adverse effects can be increased when Tramadol is combined with Ularitide.Approved, Investigational
Food Interactions
Not Available

References

General References
  1. Carstens J, Gronbaek H, Larsen HK, Pedersen EB, Vilstrup H: Effects of urodilatin on natriuresis in cirrhosis patients with sodium retention. BMC Gastroenterol. 2007 Jan 26;7:1. [PubMed:17257428]
  2. Hirsch JR, Meyer M, Forssmann WG: ANP and urodilatin: who is who in the kidney. Eur J Med Res. 2006 Oct 27;11(10):447-54. [PubMed:17107879]
External Links
PubChem Compound
16132416
PubChem Substance
175426934
ChemSpider
17289074
ChEMBL
CHEMBL2103920

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1WithdrawnTreatmentCongestive Heart Failure (CHF)1
2CompletedPreventionAcute Renal Failure (ARF) / Mortality / Renal Dysfunction1
3CompletedTreatmentAcute Decompensated Heart Failure (ADHF)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.15 mg/mLALOGPS
logP-0.94ALOGPS
logP-29ChemAxon
logS-4.4ALOGPS
pKa (Strongest Acidic)3.13ChemAxon
pKa (Strongest Basic)12.68ChemAxon
Physiological Charge5ChemAxon
Hydrogen Acceptor Count63ChemAxon
Hydrogen Donor Count60ChemAxon
Polar Surface Area1593.12 Å2ChemAxon
Rotatable Bond Count82ChemAxon
Refractivity930.43 m3·mol-1ChemAxon
Polarizability355.05 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.7865
Blood Brain Barrier-0.9853
Caco-2 permeable-0.7214
P-glycoprotein substrateSubstrate0.9271
P-glycoprotein inhibitor INon-inhibitor0.748
P-glycoprotein inhibitor IINon-inhibitor0.9108
Renal organic cation transporterNon-inhibitor0.8007
CYP450 2C9 substrateNon-substrate0.7788
CYP450 2D6 substrateNon-substrate0.806
CYP450 3A4 substrateSubstrate0.5775
CYP450 1A2 substrateNon-inhibitor0.8273
CYP450 2C9 inhibitorNon-inhibitor0.7765
CYP450 2D6 inhibitorNon-inhibitor0.8577
CYP450 2C19 inhibitorNon-inhibitor0.7557
CYP450 3A4 inhibitorNon-inhibitor0.6163
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9646
Ames testNon AMES toxic0.7993
CarcinogenicityNon-carcinogens0.809
BiodegradationNot ready biodegradable0.8598
Rat acute toxicity3.1462 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9167
hERG inhibition (predictor II)Inhibitor0.6047
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as polypeptides. These are peptides containing ten or more amino acid residues.
Kingdom
Organic compounds
Super Class
Organic Polymers
Class
Polypeptides
Sub Class
Not Available
Direct Parent
Polypeptides
Alternative Parents
Cyclic peptides / Tyrosine and derivatives / Arginine and derivatives / Phenylalanine and derivatives / Asparagine and derivatives / Leucine and derivatives / N-acyl-L-alpha-amino acids / Proline and derivatives / Serine and derivatives / Alpha amino acid amides
show 27 more
Substituents
Polypeptide / Cyclic alpha peptide / Tyrosine or derivatives / Arginine or derivatives / Phenylalanine or derivatives / Asparagine or derivatives / Leucine or derivatives / Proline or derivatives / N-acyl-alpha-amino acid / N-acyl-l-alpha-amino acid
show 53 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Protein kinase activity
Specific Function
Receptor for the atrial natriuretic peptide NPPA/ANP and the brain natriuretic peptide NPPB/BNP which are potent vasoactive hormones playing a key role in cardiovascular homeostasis. Has guanylate ...
Gene Name
NPR1
Uniprot ID
P16066
Uniprot Name
Atrial natriuretic peptide receptor 1
Molecular Weight
118918.11 Da

Drug created on October 21, 2007 16:23 / Updated on December 01, 2017 15:34