CZEN 002

Identification

Generic Name
CZEN 002
DrugBank Accession Number
DB05479
Background

CZEN-002 is a novel, non-azole anti-fungal synthetic octapeptide, derived from alpha-Melanocyte-Stimulating Hormone (a-MSH). CZEN-002 modulates inflammatory and immune responses. It has also been shown to kill Candida albicans (C. albicans), a single-celled fungal organism that causes a variety of infections, including vaginitis. This organism can invade tissues and produce fatal infections in individuals with compromised immune systems such as those suffering from HIV/AIDS or undergoing organ or bone transplants. The antimicrobial activity of CZEN-002 is unique in that it does not depend on direct damage to the microbial membrane. It appears that CZEN-002 works on a receptor in yeast that has yet to be identified.

Studies attempting to understand the candidacidal activity of derivatives of alpha-MSH have focused on the alpha-MSH amino acid sequence (6-13), which contains the invariant core sequence His-Phe-Arg-Trp (6-9) that is important for binding to the known melanocortin receptors. A second focus was on the sequence Lys-Pro-Val (11-13) that is known to be important for antimicrobial activity.

Type
Small Molecule
Groups
Investigational
Structure
Weight
Average: 1664.884
Monoisotopic: 1663.792931101
Chemical Formula
C77H109N21O19S
Synonyms
Not Available

Pharmacology

Indication

Investigated for use/treatment in candidiasis and vaginitis.

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Pharmacodynamics

CZEN-002 is a novel, non-azole anti-fungal synthetic octapeptide, derived from alpha-Melanocyte-Stimulating Hormone (a-MSH). CZEN-002 modulates inflammatory and immune responses. It has also been shown to kill Candida albicans (C. albicans). The antimicrobial activity of CZEN-002 is unique in that it does not depend on direct damage to the microbial membrane. It appears that CZEN-002 works on a receptor in yeast that has yet to be identified.

Mechanism of action

The antimicrobial activity of CZEN-002 is unique in that it does not depend on direct damage to the microbial membrane. It appears that CZEN-002 works on a receptor in yeast that has yet to be identified.

Studies attempting to understand the candidacidal activity of derivatives of alpha-MSH have focused on the alpha-MSH amino acid sequence (6-13), which contains the invariant core sequence His-Phe-Arg-Trp (6-9) that is important for binding to the known melanocortin receptors. A second focus was on the sequence Lys-Pro-Val (11-13) that is known to be important for antimicrobial activity.

TargetActionsOrganism
UMelanocyte-stimulating hormone receptorNot AvailableHumans
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

Adverse Effects
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Toxicity

Not Available

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Not Available
Food Interactions
Not Available

Categories

Drug Categories
Not Available
Classification
Not classified
Affected organisms
  • Fungi
  • Yeast and other fungi

Chemical Identifiers

UNII
Not Available
CAS number
Not Available
InChI Key
WHNFPRLDDSXQCL-PDEGJNOBSA-N
InChI
InChI=1S/C77H109N21O19S/c1-42(2)64(65(79)106)97-75(116)61-20-13-30-98(61)76(117)54(18-10-11-28-78)88-62(103)38-85-66(107)57(34-46-36-84-50-17-9-8-16-49(46)50)94-67(108)51(19-12-29-83-77(80)81)89-70(111)55(32-44-14-6-5-7-15-44)92-72(113)58(35-47-37-82-41-86-47)95-68(109)52(25-26-63(104)105)90-69(110)53(27-31-118-4)91-74(115)60(40-100)96-71(112)56(33-45-21-23-48(102)24-22-45)93-73(114)59(39-99)87-43(3)101/h5-9,14-17,21-24,36-37,41-42,51-61,64,84,99-100,102H,10-13,18-20,25-35,38-40,78H2,1-4H3,(H2,79,106)(H,82,86)(H,85,107)(H,87,101)(H,88,103)(H,89,111)(H,90,110)(H,91,115)(H,92,113)(H,93,114)(H,94,108)(H,95,109)(H,96,112)(H,97,116)(H,104,105)(H4,80,81,83)/t51-,52-,53-,54-,55-,56-,57-,58?,59-,60-,61-,64-/m0/s1
IUPAC Name
(4S)-4-[(1-{[(1S)-1-{[(1S)-1-{[(1S)-1-[({[(2S)-6-amino-1-[(2S)-2-{[(1S)-1-carbamoyl-2-methylpropyl]carbamoyl}pyrrolidin-1-yl]-1-oxohexan-2-yl]carbamoyl}methyl)carbamoyl]-2-(1H-indol-3-yl)ethyl]carbamoyl}-4-carbamimidamidobutyl]carbamoyl}-2-phenylethyl]carbamoyl}-2-(1H-imidazol-5-yl)ethyl)carbamoyl]-4-[(2S)-2-[(2S)-2-[(2S)-2-[(2S)-2-acetamido-3-hydroxypropanamido]-3-(4-hydroxyphenyl)propanamido]-3-hydroxypropanamido]-4-(methylsulfanyl)butanamido]butanoic acid
SMILES
CSCC[C@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CO)NC(C)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)NC(CC1=CN=CN1)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC1=CNC2=CC=CC=C12)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(N)=O

References

General References
  1. Csato M, Kenderessy AS, Dobozy A: Enhancement of Candida albicans killing activity of separated human epidermal cells by alpha-melanocyte stimulating hormone. Br J Dermatol. 1989 Jul;121(1):145-7. [Article]
PubChem Compound
16129664
PubChem Substance
175427016
ChemSpider
17286474

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount

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 Solubility0.0261 mg/mLALOGPS
logP-1.6ALOGPS
logP-8.9Chemaxon
logS-4.8ALOGPS
pKa (Strongest Acidic)3.47Chemaxon
pKa (Strongest Basic)11.57Chemaxon
Physiological Charge1Chemaxon
Hydrogen Acceptor Count24Chemaxon
Hydrogen Donor Count23Chemaxon
Polar Surface Area642.98 Å2Chemaxon
Rotatable Bond Count50Chemaxon
Refractivity437.71 m3·mol-1Chemaxon
Polarizability171.95 Å3Chemaxon
Number of Rings6Chemaxon
Bioavailability0Chemaxon
Rule of FiveNoChemaxon
Ghose FilterNoChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleYesChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.932
Blood Brain Barrier-0.9902
Caco-2 permeable-0.8409
P-glycoprotein substrateSubstrate0.8961
P-glycoprotein inhibitor INon-inhibitor0.8369
P-glycoprotein inhibitor IINon-inhibitor0.7796
Renal organic cation transporterNon-inhibitor0.7295
CYP450 2C9 substrateNon-substrate0.7581
CYP450 2D6 substrateNon-substrate0.7956
CYP450 3A4 substrateSubstrate0.6508
CYP450 1A2 substrateNon-inhibitor0.8291
CYP450 2C9 inhibitorNon-inhibitor0.7953
CYP450 2D6 inhibitorNon-inhibitor0.8856
CYP450 2C19 inhibitorNon-inhibitor0.7936
CYP450 3A4 inhibitorNon-inhibitor0.6388
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9465
Ames testNon AMES toxic0.725
CarcinogenicityNon-carcinogens0.8491
BiodegradationNot ready biodegradable0.9938
Rat acute toxicity2.9852 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9219
hERG inhibition (predictor II)Inhibitor0.5748
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-00dj-0011019000-ae5adcad6a52de5cbcb4
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-0006-0022049000-c400f350184a4b833a35
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-03ka-0454029000-69781611b95bca48c5d4
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-0006-6212197000-e00b810d58ef5e5ecd92
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-01ox-1359120000-1b6b0570421be0422b7b
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-05o1-2243051910-a4ad1a5fe8c049ed65a0
Chromatographic Properties
Collision Cross Sections (CCS)
Not Available

Targets

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Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Ubiquitin protein ligase binding
Specific Function
Receptor for MSH (alpha, beta and gamma) and ACTH. The activity of this receptor is mediated by G proteins which activate adenylate cyclase.
Gene Name
MC1R
Uniprot ID
Q01726
Uniprot Name
Melanocyte-stimulating hormone receptor
Molecular Weight
34705.04 Da

Drug created at November 18, 2007 18:25 / Updated at June 12, 2020 16:52