Natural Product: NPC19980

Natural Product IDNPC19980
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Olibergin A
IUPAC Name 5,7-dihydroxy-3-(4-hydroxy-2,5-dimethoxyphenyl)chromen-4-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL250269
PubChem CID 5324507
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0002506] Isoflavonoids
        • [CHEMONTID:0002586] O-methylated isoflavonoids
          • [CHEMONTID:0002605] 3'-O-methylated isoflavonoids
            • [CHEMONTID:0002690] 3'-O-methylisoflavones

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 GQGAUUMVOCWEFW-UHFFFAOYSA-N
Standard InCHI InChI=1S/C17H14O7/c1-22-13-6-11(19)14(23-2)5-9(13)10-7-24-15-4-8(18)3-12(20)16(15)17(10)21/h3-7,18-20H,1-2H3
SMILES COc1cc(c(cc1c1coc2cc(cc(c2c1=O)O)O)OC)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   330.07 Volume:   317.359
?
Van der Waals volume.
Dense:   1.04 LogP:   1.622
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.875
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.116
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   18.0
TPSA:   109.36
?
Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   3.0 Rings:   3.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.677 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.515 Fsp3:   0.118
MCE-18:   19.0
?
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:   1 PAINS Alert:   0
Colloidal aggregators:   0.483 Fluc inhibitor:   0.294
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.764
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.611
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.42 Promiscuous compounds:   0.855

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.134 MDCK Permeability:   -4.835
Pgp-inhibitor:   0.024 Pgp-substrate:   0.28
PAMPA:   0.101
?
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):   0.006
20% Bioavailability (F20%):   0.212 30% Bioavailability (F30%):   0.578
50% Bioavailability (F50%):   0.98

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.005 MRP1:   0.742
Plasma Protein Binding (PPB):   96.212% Volume Distribution (VD):   -0.468
Fu: 3.305%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.969
OATP1B3 inhibitor:   0.995 BCRP inhibitor:   0.983
BSEP inhibitor:   0.555

ADMET: Metabolism

CYP1A2-inhibitor:   0.994 CYP1A2-substrate:   0.917
CYP2C19-inhibitor:   0.05 CYP2C19-substrate:   0.088
CYP2C9-inhibitor:   0.998 CYP2C9-substrate:   0.933
CYP2D6-inhibitor:   0.999 CYP2D6-substrate:   0.994
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.423
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.996
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):  3.699 Half-life (T1/2):  1.715

ADMET: Toxicity

hERG Blockers:  0.131 hERG Blockers (10um):  0.53
Human Hepatotoxicity (H-HT):  0.501 Drug-induced Liver Injury (DILI):  0.855
AMES Toxicity:  0.633 Rat Oral Acute Toxicity:  0.569
Maximum Recommended Daily Dose:  0.861 Skin Sensitization:  0.315
Carcinogencity:  0.803 Eye Corrosion:  0.019
Eye Irritation:  0.983 Respiratory Toxicity:  0.845
Drug-induced Neurotoxicity:  0.153 Ototoxicity:  0.186
Hematotoxicity:  0.132 Drug-induced Nephrotoxicity:  0.138
Genotoxicity:  0.917 RPMI-8226 Immunitoxicity:  0.121
A549 Cytotoxicity:  0.328 Hek293 Cytotoxicity:  0.669
BCF:   0.998
?
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:   3.598
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.34
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.728
?
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
NPO24609 Millettia brandisiana Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[18039011]
NPO24609 Millettia brandisiana Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[19124248]
NPO18117 Dalbergia odorifera Species Fabaceae Eukaryota heartwood n.a. n.a. PMID[23743282]
NPO18117 Dalbergia odorifera Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[9525107]
NPO18019 Dalbergia oliveri Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24609 Millettia brandisiana Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO22420 Lignum dalbergiae odoriferae rosewood n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO18117 Dalbergia odorifera Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18117 Dalbergia odorifera Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO18117 Dalbergia odorifera Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO18019 Dalbergia oliveri Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO22420 Lignum dalbergiae odoriferae rosewood n.a. n.a. n.a. n.a. n.a. n.a. Database[TCMID]
NPO18117 Dalbergia odorifera Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO18117 Dalbergia odorifera Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO18019 Dalbergia oliveri Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18117 Dalbergia odorifera Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24609 Millettia brandisiana Species Fabaceae 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
NPT579 Cell line DLD-1 Homo sapiens IC50 > 25000.0 nM PMID[18039011]
NPT165 Cell line HeLa Homo sapiens IC50 > 25000.0 nM PMID[18039011]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 45500.0 nM PMID[23743282]

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 NPC19980 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
0.7636 Intermediate Similarity NPC309154
0.7455 Intermediate Similarity NPC239363
0.7368 Intermediate Similarity NPC254702
0.7368 Intermediate Similarity NPC45291
0.7091 Intermediate Similarity NPC78341
0.7069 Intermediate Similarity NPC142876
0.7069 Intermediate Similarity NPC483637
0.6897 Remote Similarity NPC279668
0.6897 Remote Similarity NPC278323
0.6897 Remote Similarity NPC194653
0.6897 Remote Similarity NPC481044
0.6833 Remote Similarity NPC167595
0.6724 Remote Similarity NPC200316
0.6667 Remote Similarity NPC294409
0.6667 Remote Similarity NPC490701
0.65 Remote Similarity NPC264550
0.6308 Remote Similarity NPC280937
0.6308 Remote Similarity NPC134287
0.6 Remote Similarity NPC193792
0.5965 Remote Similarity NPC87545
0.5909 Remote Similarity NPC130589
0.5909 Remote Similarity NPC268059
0.5893 Remote Similarity NPC39426
0.5893 Remote Similarity NPC608554
0.5873 Remote Similarity NPC104728
0.5821 Remote Similarity NPC479305
0.5821 Remote Similarity NPC128774
0.569 Remote Similarity NPC38065
0.5672 Remote Similarity NPC233918
0.5652 Remote Similarity NPC482075
0.5571 Remote Similarity NPC78103
0.5469 Remote Similarity NPC476055
0.5469 Remote Similarity NPC114192
0.5429 Remote Similarity NPC261470
0.5429 Remote Similarity NPC81679
0.5429 Remote Similarity NPC303197
0.5352 Remote Similarity NPC52889
0.5312 Remote Similarity NPC90665
0.5286 Remote Similarity NPC474052
0.5278 Remote Similarity NPC474960
0.5238 Remote Similarity NPC605826
0.5231 Remote Similarity NPC109187
0.5211 Remote Similarity NPC74178
0.5205 Remote Similarity NPC50960
0.5161 Remote Similarity NPC131266
0.5161 Remote Similarity NPC269451
0.5156 Remote Similarity NPC262623
0.5079 Remote Similarity NPC303644
0.5077 Remote Similarity NPC139364
0.5075 Remote Similarity NPC93552
0.5065 Remote Similarity NPC481043

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC19980 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
0.5893 Remote Similarity NPD1510 Phase 2

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