Natural Product: NPC327916

Natural Product IDNPC327916
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 [(1R)-1-(5,8-Dihydroxy-1,4-Dioxonaphthalen-2-Yl)-4-Methylpent-3-Enyl] 2-Methylbutanoate
IUPAC Name [(1R)-1-(5,8-dihydroxy-1,4-dioxonaphthalen-2-yl)-4-methylpent-3-enyl] 2-methylbutanoate
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL2288543
PubChem CID 479498
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 ODQATBANLZCROD-RGUGMKFQSA-N
Standard InCHI InChI=1S/C21H24O6/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/h6-8,10,12,17,22-23H,5,9H2,1-4H3/t12?,17-/m1/s1
SMILES CCC(C(=O)O[C@@H](C1=CC(=O)c2c(C1=O)c(O)ccc2O)CC=C(C)C)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   372.16 Volume:   386.309
?
Van der Waals volume.
Dense:   0.963 LogP:   4.662
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.91
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.119
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   7.0 Rigid Bonds:   15.0
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:   0.448 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.745 Fsp3:   0.381
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:   0.529 Fluc inhibitor:   0.667
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.847
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.453
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.459 Promiscuous compounds:   0.193

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.744 MDCK Permeability:   -4.596
Pgp-inhibitor:   0.001 Pgp-substrate:   0.021
PAMPA:   0.99
?
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):   0.011
20% Bioavailability (F20%):   0.016 30% Bioavailability (F30%):   0.082
50% Bioavailability (F50%):   0.491

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.997
Plasma Protein Binding (PPB):   97.195% Volume Distribution (VD):   0.343
Fu: 2.988%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.264
OATP1B3 inhibitor:   0.88 BCRP inhibitor:   0.001
BSEP inhibitor:   0.303

ADMET: Metabolism

CYP1A2-inhibitor:   0.099 CYP1A2-substrate:   0.353
CYP2C19-inhibitor:   0.002 CYP2C19-substrate:   0.171
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.004
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.251
CYP3A4-inhibitor:   0.003 CYP3A4-substrate:   0.851
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.999
HLM stability:   0.965
?
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):  11.968 Half-life (T1/2):  1.135

ADMET: Toxicity

hERG Blockers:  0.062 hERG Blockers (10um):  0.425
Human Hepatotoxicity (H-HT):  0.742 Drug-induced Liver Injury (DILI):  0.879
AMES Toxicity:  0.848 Rat Oral Acute Toxicity:  0.421
Maximum Recommended Daily Dose:  0.437 Skin Sensitization:  0.968
Carcinogencity:  0.699 Eye Corrosion:  0.0
Eye Irritation:  0.744 Respiratory Toxicity:  0.752
Drug-induced Neurotoxicity:  0.422 Ototoxicity:  0.532
Hematotoxicity:  0.651 Drug-induced Nephrotoxicity:  0.821
Genotoxicity:  0.895 RPMI-8226 Immunitoxicity:  0.338
A549 Cytotoxicity:  0.736 Hek293 Cytotoxicity:  0.322
BCF:   1.708
?
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:   4.885
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.113
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.843
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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]
NPO11421 Arnebia euchroma Species Boraginaceae Eukaryota n.a. n.a. n.a. PMID[12502328]
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]
NPO11776 Lithospermum erythrorhizon Species Boraginaceae Eukaryota n.a. n.a. n.a. PMID[3373224]
NPO11421 Arnebia euchroma Species Boraginaceae Eukaryota n.a. n.a. n.a. PMID[7775984]
NPO20297 Arnebia guttata Species Boraginaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11776 Lithospermum erythrorhizon Species Boraginaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11421 Arnebia euchroma 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]
NPO11421 Arnebia euchroma Species Boraginaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO20297 Arnebia guttata Species Boraginaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO11421 Arnebia euchroma 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]
NPO20297 Arnebia guttata Species Boraginaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO11421 Arnebia euchroma 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]
NPO20297 Arnebia guttata Species Boraginaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO20297 Arnebia guttata 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[TM-MC]
NPO11421 Arnebia euchroma Species Boraginaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO20297 Arnebia guttata Species Boraginaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11421 Arnebia euchroma Species Boraginaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11776 Lithospermum erythrorhizon 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
NPT786 Organism Tobacco mosaic virus Tobacco mosaic virus Inhibition = 86.1 % DOI[10.1584/jpestics.23.54]

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 NPC327916 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 NPC147542
1.0 High Similarity NPC220496
0.8776 High Similarity NPC241349
0.8776 High Similarity NPC37992
0.8163 Intermediate Similarity NPC216312
0.8163 Intermediate Similarity NPC299405
0.8 Intermediate Similarity NPC256463
0.7885 Intermediate Similarity NPC32749
0.7885 Intermediate Similarity NPC42262
0.7692 Intermediate Similarity NPC111422
0.7692 Intermediate Similarity NPC306835
0.7692 Intermediate Similarity NPC29771
0.7407 Intermediate Similarity NPC257003
0.7407 Intermediate Similarity NPC476477
0.7273 Intermediate Similarity NPC471602
0.6833 Remote Similarity NPC474300
0.6441 Remote Similarity NPC476473
0.625 Remote Similarity NPC471444
0.6 Remote Similarity NPC89664
0.5775 Remote Similarity NPC474301
0.5714 Remote Similarity NPC274085

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC327916 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