Natural Product: NPC602071

Natural Product IDNPC602071
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 ZLCZJORNMCGOTR-KBXCAEBGSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL487007
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 ZLCZJORNMCGOTR-KBXCAEBGSA-N
Standard InCHI InChI=1S/C20H20O6/c1-25-17-8-12(3-5-15(17)23)18-14(10-22)13(9-21)7-11-4-6-16(24)20(26-2)19(11)18/h3-9,14,18,22-24H,10H2,1-2H3/t14-,18+/m0/s1
SMILES COc1cc([C@H]2c3c(ccc(O)c3OC)C=C(C=O)[C@@H]2CO)ccc1O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   356.13 Volume:   360.456
?
Van der Waals volume.
Dense:   0.988 LogP:   1.964
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.222
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.694
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   18.0
TPSA:   96.22
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   3.0 Rings:   3.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.712 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.687 Fsp3:   0.25
MCE-18:   60.04
?
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:   1
Chelating Alert:   1 PAINS Alert:   0
Colloidal aggregators:   0.749 Fluc inhibitor:   0.703
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.35
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.633
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.244 Promiscuous compounds:   0.345

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.13 MDCK Permeability:   -4.813
Pgp-inhibitor:   0.128 Pgp-substrate:   0.752
PAMPA:   0.047
?
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):   0.047
20% Bioavailability (F20%):   0.839 30% Bioavailability (F30%):   0.963
50% Bioavailability (F50%):   0.997

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.038 MRP1:   0.805
Plasma Protein Binding (PPB):   90.02% Volume Distribution (VD):   -0.153
Fu: 12.266%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.972
OATP1B3 inhibitor:   0.968 BCRP inhibitor:   0.656
BSEP inhibitor:   0.391

ADMET: Metabolism

CYP1A2-inhibitor:   0.918 CYP1A2-substrate:   0.049
CYP2C19-inhibitor:   0.965 CYP2C19-substrate:   0.876
CYP2C9-inhibitor:   0.214 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.001 CYP2D6-substrate:   0.36
CYP3A4-inhibitor:   0.849 CYP3A4-substrate:   0.988
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.804
HLM stability:   0.175
?
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):  6.828 Half-life (T1/2):  1.57

ADMET: Toxicity

hERG Blockers:  0.07 hERG Blockers (10um):  0.346
Human Hepatotoxicity (H-HT):  0.683 Drug-induced Liver Injury (DILI):  0.379
AMES Toxicity:  0.841 Rat Oral Acute Toxicity:  0.396
Maximum Recommended Daily Dose:  0.443 Skin Sensitization:  0.949
Carcinogencity:  0.718 Eye Corrosion:  0.004
Eye Irritation:  0.857 Respiratory Toxicity:  0.538
Drug-induced Neurotoxicity:  0.54 Ototoxicity:  0.636
Hematotoxicity:  0.378 Drug-induced Nephrotoxicity:  0.531
Genotoxicity:  0.851 RPMI-8226 Immunitoxicity:  0.135
A549 Cytotoxicity:  0.44 Hek293 Cytotoxicity:  0.686
BCF:   0.864
?
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:   3.565
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.723
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.182
?
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
NPO14602 Vitex negundo Species Lamiaceae Eukaryota leaves n.a. n.a. PMID[12828478]
NPO14602 Vitex negundo Species Lamiaceae Eukaryota n.a. root n.a. PMID[15520511]
NPO14602 Vitex negundo Species Lamiaceae Eukaryota seeds n.a. n.a. PMID[15620254]
NPO14602 Vitex negundo Species Lamiaceae Eukaryota seeds n.a. n.a. PMID[1624939]
NPO14602 Vitex negundo Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[17027268]
NPO14602 Vitex negundo Species Lamiaceae Eukaryota Seeds n.a. n.a. PMID[19715321]
NPO14602 Vitex negundo Species Lamiaceae Eukaryota Seeds n.a. n.a. PMID[19931461]
NPO14602 Vitex negundo Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[23403897]
NPO14602 Vitex negundo Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[38163555]
NPO14602 Vitex negundo Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14602 Vitex negundo Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO14602 Vitex negundo Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO14602 Vitex negundo Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO14602 Vitex negundo Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO14602 Vitex negundo Species Lamiaceae 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

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Activity n.a. n.a. n.a. PMID[15620254]
NPT29112 Unknown Radical scavenging activity n.a. Activity n.a. n.a. n.a. PMID[15620254]

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 NPC602071 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
0.7241 Intermediate Similarity NPC82336
0.7119 Intermediate Similarity NPC78987
0.5741 Remote Similarity NPC280704
0.5455 Remote Similarity NPC480479
0.5156 Remote Similarity NPC184613
0.5079 Remote Similarity NPC9067

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC602071 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