Natural Product: NPC89664

Natural Product IDNPC89664
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 5-O-Methyl-11-O-Acetylalkannin
IUPAC Name [(1S)-1-(8-hydroxy-5-methoxy-1,4-dioxonaphthalen-2-yl)-4-methylpent-3-enyl] acetate
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1097732
PubChem CID 46833121
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 ZRTAPXYXXAPASQ-HNNXBMFYSA-N
Standard InCHI InChI=1S/C19H20O6/c1-10(2)5-7-15(25-11(3)20)12-9-14(22)17-16(24-4)8-6-13(21)18(17)19(12)23/h5-6,8-9,15,21H,7H2,1-4H3/t15-/m0/s1
SMILES COc1ccc(c2c1C(=O)C=C(C2=O)[C@@H](OC(=O)C)CC=C(C)C)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   344.13 Volume:   351.717
?
Van der Waals volume.
Dense:   0.978 LogP:   3.547
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.194
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.552
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The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   15.0
TPSA:   89.9
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   1.0 Rings:   2.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.652 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.327 Fsp3:   0.316
MCE-18:   48.0
?
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:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   1
Colloidal aggregators:   0.14 Fluc inhibitor:   0.647
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.713
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.468
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.389 Promiscuous compounds:   0.301

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.665 MDCK Permeability:   -4.551
Pgp-inhibitor:   0.061 Pgp-substrate:   0.132
PAMPA:   0.961
?
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):   0.288
20% Bioavailability (F20%):   0.195 30% Bioavailability (F30%):   0.648
50% Bioavailability (F50%):   0.884

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.856
Plasma Protein Binding (PPB):   90.75% Volume Distribution (VD):   0.302
Fu: 7.926%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.867
OATP1B3 inhibitor:   0.987 BCRP inhibitor:   0.045
BSEP inhibitor:   0.265

ADMET: Metabolism

CYP1A2-inhibitor:   0.003 CYP1A2-substrate:   0.137
CYP2C19-inhibitor:   0.003 CYP2C19-substrate:   0.027
CYP2C9-inhibitor:   0.001 CYP2C9-substrate:   0.491
CYP2D6-inhibitor:   0.001 CYP2D6-substrate:   0.16
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.674
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.999
HLM stability:   0.916
?
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):  5.886 Half-life (T1/2):  0.979

ADMET: Toxicity

hERG Blockers:  0.049 hERG Blockers (10um):  0.329
Human Hepatotoxicity (H-HT):  0.758 Drug-induced Liver Injury (DILI):  0.948
AMES Toxicity:  0.938 Rat Oral Acute Toxicity:  0.498
Maximum Recommended Daily Dose:  0.405 Skin Sensitization:  0.965
Carcinogencity:  0.825 Eye Corrosion:  0.002
Eye Irritation:  0.801 Respiratory Toxicity:  0.644
Drug-induced Neurotoxicity:  0.538 Ototoxicity:  0.381
Hematotoxicity:  0.843 Drug-induced Nephrotoxicity:  0.831
Genotoxicity:  0.969 RPMI-8226 Immunitoxicity:  0.238
A549 Cytotoxicity:  0.602 Hek293 Cytotoxicity:  0.267
BCF:   1.552
?
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:   4.253
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.832
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.271
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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
NPO12855 Alkanna cappadocica Species Boraginaceae Eukaryota n.a. n.a. n.a. PMID[20405844]
NPO12855 Alkanna cappadocica Species Boraginaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12855 Alkanna cappadocica 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
NPT139 Cell line HT-29 Homo sapiens IC50 = 620.0 nM PMID[23290052]
NPT82 Cell line MDA-MB-231 Homo sapiens IC50 = 90.0 nM PMID[23270663]
NPT306 Cell line PC-3 Homo sapiens IC50 = 780.0 nM PMID[25316316]
NPT2296 Cell line AU565 Homo sapiens IC50 = 590.0 nM PMID[25316316]
NPT65 Cell line HepG2 Homo sapiens IC50 = 870.0 nM PMID[15084123]
NPT858 Cell line LNCaP Homo sapiens IC50 = 10990.0 nM PMID[25316316]
NPT83 Cell line MCF7 Homo sapiens IC50 = 14070.0 nM PMID[23290052]
NPT165 Cell line HeLa Homo sapiens IC50 = 660.0 nM PMID[23290052]
NPT134 Cell line SK-BR-3 Homo sapiens IC50 = 440.0 nM PMID[23270663]
NPT90 Cell line DU-145 Homo sapiens IC50 = 7410.0 nM PubChem BioAssay data set
NPT2405 Cell line SAOS-2 Homo sapiens IC50 = 13810.0 nM PMID[3351854]
NPT189 Cell line Vero Chlorocebus aethiops IC50 = 590.0 nM PMID[3351854]
NPT886 Cell line NIH3T3 Mus musculus IC50 = 660.0 nM PMID[3351854]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 10190.0 nM PMID[20405844]

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 NPC89664 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
0.8704 High Similarity NPC274085
0.717 Intermediate Similarity NPC216312
0.717 Intermediate Similarity NPC299405
0.6429 Remote Similarity NPC256463
0.6207 Remote Similarity NPC111422
0.6207 Remote Similarity NPC241349
0.6207 Remote Similarity NPC306835
0.6207 Remote Similarity NPC37992
0.6207 Remote Similarity NPC29771
0.6102 Remote Similarity NPC32749
0.6102 Remote Similarity NPC42262
0.6 Remote Similarity NPC147542
0.6 Remote Similarity NPC220496
0.6 Remote Similarity NPC327916
0.6 Remote Similarity NPC257003
0.6 Remote Similarity NPC476477
0.5902 Remote Similarity NPC471602
0.5862 Remote Similarity NPC22222
0.5373 Remote Similarity NPC474300
0.5246 Remote Similarity NPC281513
0.5143 Remote Similarity NPC471444

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC89664 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