Natural Product: NPC37080

Natural Product IDNPC37080
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 ZGQONWTUIANWFM-QJXUFPCYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 5317332
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0002448] Benzenoids
      • [CHEMONTID:0000023] Naphthalenes
        • [CHEMONTID:0000153] Naphthoquinones

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 ZGQONWTUIANWFM-QJXUFPCYSA-N
Standard InCHI InChI=1S/C21H22O6/c1-5-12(4)21(26)27-17(9-6-11(2)3)13-10-16(24)18-14(22)7-8-15(23)19(18)20(13)25/h5-8,10,17,22-23H,9H2,1-4H3/b12-5+/t17-/m0/s1
SMILES C/C=C(C)/C(=O)O[C@@H](CC=C(C)C)C1=CC(=O)c2c(ccc(c2C1=O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   370.14 Volume:   383.672
?
Van der Waals volume.
Dense:   0.965 LogP:   4.089
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.605
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.116
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   16.0
TPSA:   100.9
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   2.0 Rings:   2.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.355 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.637 Fsp3:   0.286
MCE-18:   51.0
?
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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   1
Colloidal aggregators:   0.509 Fluc inhibitor:   0.655
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.669
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.612
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.575 Promiscuous compounds:   0.269

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.817 MDCK Permeability:   -4.55
Pgp-inhibitor:   0.004 Pgp-substrate:   0.018
PAMPA:   0.992
?
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):   0.025
20% Bioavailability (F20%):   0.035 30% Bioavailability (F30%):   0.316
50% Bioavailability (F50%):   0.663

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.96
Plasma Protein Binding (PPB):   95.727% Volume Distribution (VD):   0.606
Fu: 4.381%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.898
OATP1B3 inhibitor:   0.962 BCRP inhibitor:   0.002
BSEP inhibitor:   0.261

ADMET: Metabolism

CYP1A2-inhibitor:   0.068 CYP1A2-substrate:   0.951
CYP2C19-inhibitor:   0.001 CYP2C19-substrate:   0.861
CYP2C9-inhibitor:   0.006 CYP2C9-substrate:   0.016
CYP2D6-inhibitor:   0.002 CYP2D6-substrate:   0.611
CYP3A4-inhibitor:   0.014 CYP3A4-substrate:   0.994
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.997
HLM stability:   0.985
?
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):  12.027 Half-life (T1/2):  1.405

ADMET: Toxicity

hERG Blockers:  0.031 hERG Blockers (10um):  0.367
Human Hepatotoxicity (H-HT):  0.694 Drug-induced Liver Injury (DILI):  0.926
AMES Toxicity:  0.877 Rat Oral Acute Toxicity:  0.585
Maximum Recommended Daily Dose:  0.547 Skin Sensitization:  0.983
Carcinogencity:  0.831 Eye Corrosion:  0.001
Eye Irritation:  0.854 Respiratory Toxicity:  0.796
Drug-induced Neurotoxicity:  0.213 Ototoxicity:  0.404
Hematotoxicity:  0.738 Drug-induced Nephrotoxicity:  0.784
Genotoxicity:  0.962 RPMI-8226 Immunitoxicity:  0.35
A549 Cytotoxicity:  0.732 Hek293 Cytotoxicity:  0.345
BCF:   1.659
?
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:   4.868
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.25
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.916
?
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
NPO11776 Lithospermum erythrorhizon Species Boraginaceae Eukaryota n.a. root n.a. DOI[10.1007/s11418-007-0221-0]
NPO11776 Lithospermum erythrorhizon Species Boraginaceae Eukaryota n.a. n.a. n.a. DOI[10.1016/0031-9422(83)80138-1]
NPO11776 Lithospermum erythrorhizon Species Boraginaceae Eukaryota n.a. n.a. n.a. PMID[17157006]
NPO11776 Lithospermum erythrorhizon Species Boraginaceae Eukaryota n.a. n.a. n.a. PMID[19217780]
NPO14827 Rhus chinensis Species Anacardiaceae Eukaryota Roots n.a. n.a. PMID[32031812]
NPO11776 Lithospermum erythrorhizon Species Boraginaceae Eukaryota n.a. n.a. n.a. PMID[3373224]
NPO11776 Lithospermum erythrorhizon Species Boraginaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11776 Lithospermum erythrorhizon Species Boraginaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO14827 Rhus chinensis Species Anacardiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO24872 Arnebia nobilis Species Boraginaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO14827 Rhus chinensis Species Anacardiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO24872 Arnebia nobilis Species Boraginaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO11776 Lithospermum erythrorhizon Species Boraginaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO24872 Arnebia nobilis Species Boraginaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO11776 Lithospermum erythrorhizon Species Boraginaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO14827 Rhus chinensis Species Anacardiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO14827 Rhus chinensis Species Anacardiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO11776 Lithospermum erythrorhizon Species Boraginaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO11776 Lithospermum erythrorhizon Species Boraginaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14827 Rhus chinensis Species Anacardiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24872 Arnebia nobilis Species Boraginaceae 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

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 NPC37080 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
0.8542 High Similarity NPC256463
0.8333 Intermediate Similarity NPC216312
0.8333 Intermediate Similarity NPC299405
0.82 Intermediate Similarity NPC306835
0.8039 Intermediate Similarity NPC32749
0.8039 Intermediate Similarity NPC42262
0.7885 Intermediate Similarity NPC257003
0.7885 Intermediate Similarity NPC476477
0.7843 Intermediate Similarity NPC111422
0.7843 Intermediate Similarity NPC241349
0.7843 Intermediate Similarity NPC37992
0.7843 Intermediate Similarity NPC29771
0.7736 Intermediate Similarity NPC471602
0.7547 Intermediate Similarity NPC147542
0.7547 Intermediate Similarity NPC220496
0.7547 Intermediate Similarity NPC327916
0.6667 Remote Similarity NPC474300
0.6613 Remote Similarity NPC471444
0.6271 Remote Similarity NPC476473
0.6102 Remote Similarity NPC89664
0.5806 Remote Similarity NPC274085
0.5634 Remote Similarity NPC474301

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC37080 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