Natural Product: NPC605639

Natural Product IDNPC605639
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 APZYKUZPJCQGPP-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL332479
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]

The Chemical Classification was calculated by Classyfire, a software for chemical taxonomy calculation. Reference: DOI:10.1186/s13321-016-0174-y.

  Chemical Representations

Standard InCHIKey APZYKUZPJCQGPP-UHFFFAOYSA-N
Standard InCHI InChI=1S/C17H23NO3/c19-17(18-10-4-1-5-11-18)7-3-2-6-14-8-9-15-16(12-14)21-13-20-15/h8-9,12H,1-7,10-11,13H2
SMILES O=C(CCCCc1ccc2c(c1)OCO2)N1CCCCC1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   289.17 Volume:   303.74
?
Van der Waals volume.
Dense:   0.952 LogP:   3.305
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.907
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.727
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   17.0
TPSA:   38.77
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   0.0 Rings:   3.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.782 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   1.939 Fsp3:   0.588
MCE-18:   34.222
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Accepted GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.01 Fluc inhibitor:   0.232
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.025
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.422
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.007 Promiscuous compounds:   0.06

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.623 MDCK Permeability:   -4.652
Pgp-inhibitor:   0.707 Pgp-substrate:   0.102
PAMPA:   0.037
?
The experimental data for Peff was logarithmically transformed (logPeff). Molecules with log Peff values below 2.0 were classified as low-permeability (Category 0), while those with log Peff values exceeding 2.5 were classified as high-permeability (Category 1).
 Human Intestinal Absorption (HIA):   0.007
20% Bioavailability (F20%):   0.046 30% Bioavailability (F30%):   0.002
50% Bioavailability (F50%):   0.472

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.715 MRP1:   0.296
Plasma Protein Binding (PPB):   90.719% Volume Distribution (VD):   -0.062
Fu: 8.487%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.774
OATP1B3 inhibitor:   0.784 BCRP inhibitor:   0.025
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.581 CYP1A2-substrate:   0.983
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.88
CYP2C9-inhibitor:   1.0 CYP2C9-substrate:   0.999
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   1.0
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   0.003
CYP2B6-substrate:   0.03 CYP2C8-inhibitor:   0.817
HLM stability:   0.996
?
Human liver microsomal (HLM) stability. Category 0: stable+ (HLM > 30 min); Category 1: unstable- (HLM ≤ 30 min). The output value is the probability of human liver microsomal instability, where a value closer to 1 indicates a higher likelihood of instability.

ADMET: Excretion

Clearance (CL):  4.386 Half-life (T1/2):  0.254

ADMET: Toxicity

hERG Blockers:  0.47 hERG Blockers (10um):  0.561
Human Hepatotoxicity (H-HT):  0.617 Drug-induced Liver Injury (DILI):  0.341
AMES Toxicity:  0.323 Rat Oral Acute Toxicity:  0.318
Maximum Recommended Daily Dose:  0.588 Skin Sensitization:  0.624
Carcinogencity:  0.546 Eye Corrosion:  0.051
Eye Irritation:  0.762 Respiratory Toxicity:  0.65
Drug-induced Neurotoxicity:  0.7 Ototoxicity:  0.23
Hematotoxicity:  0.278 Drug-induced Nephrotoxicity:  0.581
Genotoxicity:  0.027 RPMI-8226 Immunitoxicity:  0.073
A549 Cytotoxicity:  0.1 Hek293 Cytotoxicity:  0.432
BCF:   0.956
?
Bioconcentration factors are used for considering secondary poisoning potential and assessing risks to human health via the food chain. The unit is -log10[(mg/L)/(1000*MW)].
 IGC50:   3.622
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.313
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.571
?
96 hour fathead minnow LC50. The unit of LC50FM is -log10[(mg/L)/(1000*MW)].

  Species Source

Organism ID Organism Name Taxonomy Level Family SuperKingdom Isolation Part Collection Location Collection Time Reference
NPO20606 Piper tuberculatum Species Piperaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20606 Piper tuberculatum Species Piperaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO20606 Piper tuberculatum Species Piperaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO20606 Piper tuberculatum Species Piperaceae Eukaryota n.a. n.a. n.a. Database[UNPD]

Note for Reference:
In addition to directly collecting NP source organism data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated them from below databases:
☉ UNPD: Universal Natural Products Database [PMID: 23638153].
☉ StreptomeDB: a database of streptomycetes natural products [PMID: 33051671].
☉ TM-MC: a database of medicinal materials and chemical compounds in Northeast Asian traditional medicine [PMID: 26156871].
☉ TCM@Taiwan: a Traditional Chinese Medicine database [PMID: 21253603].
☉ TCMID: a Traditional Chinese Medicine database [PMID: 29106634].
☉ TCMSP: The traditional Chinese medicine systems pharmacology database and analysis platform [PMID: 24735618].
☉ HerDing: a herb recommendation system to treat diseases using genes and chemicals [PMID: 26980517].
☉ MetaboLights: a metabolomics database [PMID: 27010336].
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].



  NP Quantity Composition/Concentration

Organism ID Organism Name Organism Material Preparation Organism Part NP Quantity (Standard) NP Quantity (Minimum) NP Quantity (Maximum) Quantity Unit Reference

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP quantitative records for specific NP domains (e.g., NPS from foods or herbs) from domain-specific databases. These databases include:
☉ DUKE: Dr. Duke's Phytochemical and Ethnobotanical Databases.
☉ PHENOL EXPLORER: is the first comprehensive database on polyphenol content in foods [PMID: 24103452], its homepage can be accessed at here.
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].



 Biological Activity

Molecular-level activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT2794 Individual protein Quinolone resistance protein norA Staphylococcus aureus logPF = 1.3 n.a. PMID[19523722]
NPT1488 Individual protein Monoamine oxidase A Rattus norvegicus IC50 > 100000.0 nM PMID[22475561]
NPT1487 Individual protein Monoamine oxidase B Rattus norvegicus IC50 = 1970.0 nM PMID[22475561]
NPT2794 Individual protein Quinolone resistance protein norA Staphylococcus aureus FC = 2.0 n.a. PMID[18848780]
NPT2794 Individual protein Quinolone resistance protein norA Staphylococcus aureus FC = 2.0 n.a. PMID[19523722]
NPT2794 Individual protein Quinolone resistance protein norA Staphylococcus aureus MIC > 100.0 ug.mL-1 PMID[19523722]
NPT2794 Individual protein Quinolone resistance protein norA Staphylococcus aureus FC = 0.0 n.a. PMID[18848780]
NPT2794 Individual protein Quinolone resistance protein norA Staphylococcus aureus PF = 20.0 n.a. PMID[19523722]
NPT2794 Individual protein Quinolone resistance protein norA Staphylococcus aureus MEC = 50.0 ug ml-1 PMID[19523722]
NPT472 Individual protein Vanilloid receptor Homo sapiens EC50 = 6309.57 nM PMID[20381363]
NPT472 Individual protein Vanilloid receptor Homo sapiens Emax = 90.0 % PMID[20381363]
NPT472 Individual protein Vanilloid receptor Homo sapiens Activity n.a. n.a. n.a. PMID[20381363]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT580 Organism Trypanosoma cruzi Trypanosoma cruzi IC50 = 19000.0 nM PMID[20185316]
NPT580 Organism Trypanosoma cruzi Trypanosoma cruzi IC50 = 11520.0 nM PMID[15177472]
NPT580 Organism Trypanosoma cruzi Trypanosoma cruzi IC50 n.a. n.a. n.a. DOI[10.1007/s00044-008-9161-9]
NPT580 Organism Trypanosoma cruzi Trypanosoma cruzi IC50 = 19410.0 nM PMID[15177472]
NPT29139 Protein complex Glutamate NMDA receptor; GRIN1/GRIN2B Homo sapiens Activity n.a. n.a. n.a. PMID[38665828]

In vivo activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference





 Experimental ADME

Experiment Model Experiment Tissue ADME Type ADME Relation ADME Value ADME Unit Reference





 Experimental Toxicity

Quantitative toxicity

Experiment Model Experiment Organism Toxicity Type Toxicity Relation Toxicity Value Toxicity Unit Reference

Common Abbreviations:
LC: Lethal Concentration; LD: Lethal Dose; LT:Lethal Time; NOAEL: No-observed-adverse-effect Level; BMDL: Benchmark Dose Lower Confidence Limit; BMD: Benchmark Dose; BMC:Benchmark Concentration; LOAEL: Lowest Observed Adverse Effect Level; RfD:Reference Dose; RfC:Reference Concentration; MRL: Minimal Risk Level; MEG: Maximum Exposure Guideline; PAC: Protective Action Criteria

Categorical toxicity labels

Hepatotoxicity Carcinogenicity Mutagenicity Cardiotoxicity Respiratory Toxicity Eye Irritation Endocrine Disruption
Hepatotoxicity Carcinogenicity Mutagenicity Cardiotoxicity Respiratory Toxicity Eye Irritation Endocrine Disruption

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP toxicity records from domain-specific databases. These databases include:
☉ ToxValDB: a curated database that compiles quantitative toxicity values for chemicals from diverse public sources to support toxicological research and risk assessment.
☉ TOXRIC: a comprehensive, free-to-access, online database providing toxicological/feature data. The toxicity labels are retrieved from this database. [PMID: 36400569]


  Chemically structural similarity

Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes approximately 50,000 NPs with experimentally-derived bioactivity available in NPASS)

Similarity is measured using the Tanimoto coefficient (Tc) , which compares the binary fingerprints of two molecules. Tc is calculated as the intersection divided by the union of '1' bits in the fingerprints, ranging from 0 to 1, with 1 indicating highest similarity.

●  The left chart: Distribution of similarity level between NPC605639 and all remaining natural products in the NPASS database.
●  The right table: Most similar natural products (Tc>=0.5 or Top200).

Similarity Score Similarity Level Natural Product ID
0.9767 High Similarity NPC608515
0.6667 Remote Similarity NPC248505
0.6379 Remote Similarity NPC95366
0.6296 Remote Similarity NPC252107
0.5789 Remote Similarity NPC194359
0.5789 Remote Similarity NPC28641
0.5789 Remote Similarity NPC145446
0.5789 Remote Similarity NPC180647
0.5789 Remote Similarity NPC137172
0.5789 Remote Similarity NPC225745
0.569 Remote Similarity NPC477705
0.569 Remote Similarity NPC477706
0.5424 Remote Similarity NPC88345
0.5294 Remote Similarity NPC470708
0.5156 Remote Similarity NPC470855
0.5088 Remote Similarity NPC477694
0.5082 Remote Similarity NPC318862

Similar Clinical/Approved Drugs

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules.

●  The left chart: Distribution of similarity level between NPC605639 and all drugs/candidates.
●  The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

Similarity Score Similarity Level Drug ID Developmental Stage
NPD

Bioactivity similarity

  Bioactivity similarity

Similar Natural Products in NPASS

Similarity level is defined by Bioactivity similarity was calculated based on bioactivity descriptors of compounds. The bioactivity descriptors were calculated by a recently developed AI algorithm Chemical Checker (CC) [Nature Biotechnology, 38:1087–1096, 2020; Nature Communications, 12:3932, 2021], which evaluated bioactivity similarities at five levels:
☉ A: chemistry similarity;
☉ B: biological targets similarity;
☉ C: networks similarity;
☉ D: cell-based bioactivity similarity;
☉ E: similarity based on clinical data.
Those 5 categories of CC bioactivity descriptors were calculated and then subjected to manifold projection using UMAP algorithm, to project all NPs on a 2-Dimensional space. The current NP was highlighted with a small circle in the 2-D map. Below figures: left-to-right, A-to-E.

A: chemistry similarity
B: biological targets similarity
C: networks similarity
D: cell-based bioactivity similarity
E: similarity based on clinical data