Natural Product: NPC220228

Natural Product IDNPC220228
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 GVVXPMORGFYVOO-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 267400
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000279] Alkaloids and derivatives
      • [CHEMONTID:0000381] Aporphines

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 GVVXPMORGFYVOO-UHFFFAOYSA-N
Standard InCHI InChI=1S/C19H21NO4/c1-22-15-9-12-11(7-14(15)21)6-13-17-10(4-5-20-13)8-16(23-2)19(24-3)18(12)17/h7-9,13,20-21H,4-6H2,1-3H3
SMILES COc1cc2-c3c4c(CCNC4Cc2cc1O)cc(c3OC)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   327.15 Volume:   333.293
?
Van der Waals volume.
Dense:   0.982 LogP:   1.311
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.709
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.198
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   20.0
TPSA:   59.95
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   2.0 Rings:   4.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.908 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.109 Fsp3:   0.368
MCE-18:   72.769
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Rejected GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   1 PAINS Alert:   0
Colloidal aggregators:   0.572 Fluc inhibitor:   0.027
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.407
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.274
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.002 Promiscuous compounds:   0.473

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.161 MDCK Permeability:   -4.903
Pgp-inhibitor:   0.05 Pgp-substrate:   0.843
PAMPA:   0.1
?
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):   0.187
20% Bioavailability (F20%):   0.23 30% Bioavailability (F30%):   0.315
50% Bioavailability (F50%):   0.948

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.051 MRP1:   0.941
Plasma Protein Binding (PPB):   40.893% Volume Distribution (VD):   0.052
Fu: 55.082%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.906
OATP1B3 inhibitor:   0.995 BCRP inhibitor:   0.743
BSEP inhibitor:   0.83

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.002
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.908 CYP2C9-substrate:   0.843
CYP2D6-inhibitor:   0.998 CYP2D6-substrate:   0.008
CYP3A4-inhibitor:   0.966 CYP3A4-substrate:   0.013
CYP2B6-substrate:   0.993 CYP2C8-inhibitor:   0.001
HLM stability:   0.522
?
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):  5.436 Half-life (T1/2):  2.272

ADMET: Toxicity

hERG Blockers:  0.5 hERG Blockers (10um):  0.693
Human Hepatotoxicity (H-HT):  0.661 Drug-induced Liver Injury (DILI):  0.221
AMES Toxicity:  0.775 Rat Oral Acute Toxicity:  0.748
Maximum Recommended Daily Dose:  0.861 Skin Sensitization:  0.954
Carcinogencity:  0.317 Eye Corrosion:  0.003
Eye Irritation:  0.183 Respiratory Toxicity:  0.987
Drug-induced Neurotoxicity:  0.86 Ototoxicity:  0.761
Hematotoxicity:  0.149 Drug-induced Nephrotoxicity:  0.679
Genotoxicity:  0.537 RPMI-8226 Immunitoxicity:  0.126
A549 Cytotoxicity:  0.196 Hek293 Cytotoxicity:  0.305
BCF:   1.307
?
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:   3.716
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.07
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.25
?
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
NPO26237 Piper longum Species Piperaceae Eukaryota n.a. n.a. n.a. PMID[16872768]
NPO4682 Lindera aggregata Species Lauraceae Eukaryota n.a. leaf n.a. PMID[17999353]
NPO3079 Cassytha filiformis Species Lauraceae Eukaryota n.a. n.a. n.a. PMID[18217715]
NPO29110 Litsea cubeba Species Lauraceae Eukaryota n.a. aerial part n.a. PMID[18991207]
NPO4682 Lindera aggregata Species Lauraceae Eukaryota Roots; Tubers n.a. n.a. PMID[19639966]
NPO26237 Piper longum Species Piperaceae Eukaryota fruits n.a. n.a. PMID[20839888]
NPO29110 Litsea cubeba Species Lauraceae Eukaryota essential oil Tibet n.a. PMID[20944522]
NPO26237 Piper longum Species Piperaceae Eukaryota n.a. n.a. n.a. PMID[23434420]
NPO29110 Litsea cubeba Species Lauraceae Eukaryota Twigs n.a. n.a. PMID[28541690]
NPO21807 Lindera umbellata Species Lauraceae Eukaryota n.a. n.a. n.a. PMID[32933154]
NPO29110 Litsea cubeba Species Lauraceae Eukaryota n.a. n.a. n.a. PMID[36552598]
NPO29110 Litsea cubeba Species Lauraceae Eukaryota n.a. n.a. n.a. PMID[37746728]
NPO29110 Litsea cubeba Species Lauraceae Eukaryota n.a. n.a. n.a. PMID[39013008]
NPO29110 Litsea cubeba Species Lauraceae Eukaryota n.a. n.a. n.a. PMID[39395223]
NPO3079 Cassytha filiformis Species Lauraceae Eukaryota n.a. n.a. n.a. Database[Article]
NPO31274 Lindera strychnifolia Species Tineidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3079 Cassytha filiformis Species Lauraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO963 Litsea pungens Species Lauraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21807 Lindera umbellata Species Lauraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29110 Litsea cubeba Species Lauraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4682 Lindera aggregata Species Lauraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26237 Piper longum Species Piperaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO963 Litsea pungens Species Lauraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO21807 Lindera umbellata Species Lauraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO3079 Cassytha filiformis Species Lauraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO26237 Piper longum Species Piperaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO29110 Litsea cubeba Species Lauraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO31274 Lindera strychnifolia Species Tineidae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO21807 Lindera umbellata Species Lauraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO4682 Lindera aggregata Species Lauraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO3079 Cassytha filiformis Species Lauraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO26237 Piper longum Species Piperaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO29110 Litsea cubeba Species Lauraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO963 Litsea pungens Species Lauraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO21807 Lindera umbellata Species Lauraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO963 Litsea pungens Species Lauraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO26237 Piper longum Species Piperaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO31274 Lindera strychnifolia Species Tineidae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO26237 Piper longum Species Piperaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO4682 Lindera aggregata Species Lauraceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO29110 Litsea cubeba Species Lauraceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO29110 Litsea cubeba Species Lauraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26237 Piper longum Species Piperaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4682 Lindera aggregata Species Lauraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3079 Cassytha filiformis Species Lauraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21807 Lindera umbellata Species Lauraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO963 Litsea pungens Species Lauraceae 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
NPT4437 Individual protein Aryl hydrocarbon receptor Mus musculus Activity n.a. n.a. n.a. PMID[37154394]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT4590 Cell line EL4 Mus musculus IC50 = 48410.0 nM PMID[37154394]

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 NPC220228 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
1.0 High Similarity NPC69712
0.8276 Intermediate Similarity NPC155442
0.8276 Intermediate Similarity NPC312918
0.7636 Intermediate Similarity NPC26240
0.7119 Intermediate Similarity NPC302713
0.7069 Intermediate Similarity NPC609330
0.678 Remote Similarity NPC298008
0.6557 Remote Similarity NPC192135
0.6441 Remote Similarity NPC203784
0.6441 Remote Similarity NPC170503
0.6441 Remote Similarity NPC126519
0.6308 Remote Similarity NPC186546
0.6032 Remote Similarity NPC6152
0.6 Remote Similarity NPC152212
0.6 Remote Similarity NPC28341
0.5781 Remote Similarity NPC608930
0.5738 Remote Similarity NPC66341
0.5714 Remote Similarity NPC610238
0.5625 Remote Similarity NPC81247
0.5625 Remote Similarity NPC35627
0.5625 Remote Similarity NPC299687
0.5625 Remote Similarity NPC476573
0.5507 Remote Similarity NPC135772
0.5362 Remote Similarity NPC57036
0.5362 Remote Similarity NPC600117
0.5303 Remote Similarity NPC474507
0.5238 Remote Similarity NPC204947
0.5075 Remote Similarity NPC189470
0.5075 Remote Similarity NPC191213

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC220228 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