Natural Product: NPC168059

Natural Product IDNPC168059
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 3-(4-Hydroxy-2,3-Dimethoxyphenyl)-2H-Chromen-7-Ol
IUPAC Name 3-(4-hydroxy-2,3-dimethoxyphenyl)-2H-chromen-7-ol
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1989020
PubChem CID 338286
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

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 JGINXZCTOGQYKS-UHFFFAOYSA-N
Standard InCHI InChI=1S/C17H16O5/c1-20-16-13(5-6-14(19)17(16)21-2)11-7-10-3-4-12(18)8-15(10)22-9-11/h3-8,18-19H,9H2,1-2H3
SMILES COc1c(ccc(c1OC)O)C1=Cc2ccc(cc2OC1)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   300.1 Volume:   302.415
?
Van der Waals volume.
Dense:   0.992 LogP:   3.018
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.388
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.491
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   17.0
TPSA:   68.15
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   2.0 Rings:   3.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.912 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.688 Fsp3:   0.176
MCE-18:   35.7
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Accepted GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   1 PAINS Alert:   0
Colloidal aggregators:   0.611 Fluc inhibitor:   0.953
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.784
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.512
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.357 Promiscuous compounds:   0.525

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.948 MDCK Permeability:   -4.784
Pgp-inhibitor:   0.001 Pgp-substrate:   0.117
PAMPA:   0.393
?
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):   0.001
20% Bioavailability (F20%):   0.574 30% Bioavailability (F30%):   0.274
50% Bioavailability (F50%):   0.986

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.67 MRP1:   0.953
Plasma Protein Binding (PPB):   92.031% Volume Distribution (VD):   -0.121
Fu: 10.232%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.801
OATP1B3 inhibitor:   0.975 BCRP inhibitor:   0.209
BSEP inhibitor:   0.341

ADMET: Metabolism

CYP1A2-inhibitor:   0.943 CYP1A2-substrate:   0.212
CYP2C19-inhibitor:   0.008 CYP2C19-substrate:   0.151
CYP2C9-inhibitor:   0.944 CYP2C9-substrate:   0.648
CYP2D6-inhibitor:   0.99 CYP2D6-substrate:   0.803
CYP3A4-inhibitor:   0.758 CYP3A4-substrate:   0.884
CYP2B6-substrate:   0.17 CYP2C8-inhibitor:   0.606
HLM stability:   0.345
?
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):  6.356 Half-life (T1/2):  1.393

ADMET: Toxicity

hERG Blockers:  0.29 hERG Blockers (10um):  0.62
Human Hepatotoxicity (H-HT):  0.562 Drug-induced Liver Injury (DILI):  0.402
AMES Toxicity:  0.651 Rat Oral Acute Toxicity:  0.486
Maximum Recommended Daily Dose:  0.705 Skin Sensitization:  0.651
Carcinogencity:  0.766 Eye Corrosion:  0.007
Eye Irritation:  0.9 Respiratory Toxicity:  0.69
Drug-induced Neurotoxicity:  0.565 Ototoxicity:  0.385
Hematotoxicity:  0.229 Drug-induced Nephrotoxicity:  0.285
Genotoxicity:  0.466 RPMI-8226 Immunitoxicity:  0.154
A549 Cytotoxicity:  0.342 Hek293 Cytotoxicity:  0.704
BCF:   1.351
?
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:   3.702
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.43
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.956
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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
NPO10080 Teucrium betonicum Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10080 Teucrium betonicum 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
NPT367 Cell line MDA-N Homo sapiens GI50 n.a. 3681.29 nM PubChem BioAssay data set
NPT368 Cell line SN12C Homo sapiens GI50 n.a. 23014.42 nM PubChem BioAssay data set
NPT369 Cell line ACHN Homo sapiens GI50 n.a. 6561.45 nM PubChem BioAssay data set
NPT370 Cell line NCI-H23 Homo sapiens GI50 n.a. 22284.35 nM PubChem BioAssay data set
NPT371 Cell line UO-31 Homo sapiens GI50 n.a. 11641.26 nM PubChem BioAssay data set
NPT372 Cell line HOP-92 Homo sapiens GI50 n.a. 24043.63 nM PubChem BioAssay data set
NPT116 Cell line HL-60 Homo sapiens GI50 n.a. 2818.38 nM PubChem BioAssay data set
NPT90 Cell line DU-145 Homo sapiens GI50 n.a. 26730.06 nM PubChem BioAssay data set
NPT374 Cell line SF-539 Homo sapiens GI50 n.a. 16330.52 nM PubChem BioAssay data set
NPT373 Cell line SK-MEL-5 Homo sapiens GI50 n.a. 16106.46 nM PubChem BioAssay data set
NPT375 Cell line Malme-3M Homo sapiens GI50 n.a. 18879.91 nM PubChem BioAssay data set
NPT111 Cell line K562 Homo sapiens GI50 n.a. 7079.46 nM PubChem BioAssay data set
NPT376 Cell line A498 Homo sapiens GI50 n.a. 27861.21 nM PubChem BioAssay data set
NPT377 Cell line OVCAR-3 Homo sapiens GI50 n.a. 14859.36 nM PubChem BioAssay data set
NPT112 Cell line MOLT-4 Homo sapiens GI50 n.a. 6823.39 nM PubChem BioAssay data set
NPT379 Cell line HOP-62 Homo sapiens GI50 n.a. 20941.12 nM PubChem BioAssay data set
NPT378 Cell line NCI/ADR-RES Homo sapiens GI50 n.a. 14487.72 nM PubChem BioAssay data set
NPT380 Cell line U-251 Homo sapiens GI50 n.a. 26001.6 nM PubChem BioAssay data set
NPT381 Cell line OVCAR-8 Homo sapiens GI50 n.a. 17988.71 nM PubChem BioAssay data set
NPT382 Cell line OVCAR-5 Homo sapiens GI50 n.a. 30130.06 nM PubChem BioAssay data set
NPT82 Cell line MDA-MB-231 Homo sapiens GI50 n.a. 20653.8 nM PubChem BioAssay data set
NPT383 Cell line SNB-19 Homo sapiens GI50 n.a. 55335.01 nM PubChem BioAssay data set
NPT385 Cell line SR Homo sapiens GI50 n.a. 2147.83 nM PubChem BioAssay data set
NPT384 Cell line TK-10 Homo sapiens GI50 n.a. 55207.74 nM PubChem BioAssay data set
NPT323 Cell line SW-620 Homo sapiens GI50 n.a. 26668.59 nM PubChem BioAssay data set
NPT455 Cell line NCI-H522 Homo sapiens GI50 n.a. 2344.23 nM PubChem BioAssay data set
NPT386 Cell line KM12 Homo sapiens GI50 n.a. 7328.25 nM PubChem BioAssay data set
NPT388 Cell line NCI-H322M Homo sapiens GI50 n.a. 26977.39 nM PubChem BioAssay data set
NPT387 Cell line M14 Homo sapiens GI50 n.a. 20989.4 nM PubChem BioAssay data set
NPT389 Cell line RPMI-8226 Homo sapiens GI50 n.a. 3507.52 nM PubChem BioAssay data set
NPT456 Cell line OVCAR-4 Homo sapiens GI50 n.a. 23878.11 nM PubChem BioAssay data set
NPT390 Cell line LOX IMVI Homo sapiens GI50 n.a. 26061.54 nM PubChem BioAssay data set
NPT457 Cell line BT-549 Homo sapiens GI50 n.a. 23550.49 nM PubChem BioAssay data set
NPT147 Cell line SK-MEL-2 Homo sapiens GI50 n.a. 23442.29 nM PubChem BioAssay data set
NPT391 Cell line HCC 2998 Homo sapiens GI50 n.a. 20989.4 nM PubChem BioAssay data set
NPT81 Cell line A549 Homo sapiens GI50 n.a. 24774.22 nM PubChem BioAssay data set
NPT392 Cell line SNB-75 Homo sapiens GI50 n.a. 14859.36 nM PubChem BioAssay data set
NPT148 Cell line HCT-15 Homo sapiens GI50 n.a. 14125.38 nM PubChem BioAssay data set
NPT393 Cell line HCT-116 Homo sapiens GI50 n.a. 24322.04 nM PubChem BioAssay data set
NPT395 Cell line SF-268 Homo sapiens GI50 n.a. 20230.19 nM PubChem BioAssay data set
NPT394 Cell line EKVX Homo sapiens GI50 n.a. 15066.07 nM PubChem BioAssay data set
NPT306 Cell line PC-3 Homo sapiens GI50 n.a. 18620.87 nM PubChem BioAssay data set
NPT83 Cell line MCF7 Homo sapiens GI50 n.a. 32359.37 nM PubChem BioAssay data set
NPT146 Cell line SK-OV-3 Homo sapiens GI50 n.a. 23988.33 nM PubChem BioAssay data set
NPT396 Cell line T47D Homo sapiens GI50 n.a. 25644.84 nM PubChem BioAssay data set
NPT397 Cell line NCI-H460 Homo sapiens GI50 n.a. 31045.6 nM PubChem BioAssay data set
NPT308 Cell line CAKI-1 Homo sapiens GI50 n.a. 8810.49 nM PubChem BioAssay data set
NPT398 Cell line UACC-62 Homo sapiens GI50 n.a. 16218.1 nM PubChem BioAssay data set
NPT399 Cell line SF-295 Homo sapiens GI50 n.a. 22803.42 nM PubChem BioAssay data set
NPT400 Cell line MDA-MB-435 Homo sapiens GI50 n.a. 7638.36 nM PubChem BioAssay data set
NPT458 Cell line IGROV-1 Homo sapiens GI50 n.a. 25763.21 nM PubChem BioAssay data set
NPT402 Cell line Hs-578T Homo sapiens GI50 n.a. 19453.6 nM PubChem BioAssay data set
NPT401 Cell line 786-0 Homo sapiens GI50 n.a. 16292.96 nM PubChem BioAssay data set
NPT403 Cell line UACC-257 Homo sapiens GI50 n.a. 30338.91 nM PubChem BioAssay data set
NPT404 Cell line CCRF-CEM Homo sapiens GI50 n.a. 4365.16 nM PubChem BioAssay data set
NPT139 Cell line HT-29 Homo sapiens GI50 n.a. 30408.85 nM PubChem BioAssay data set
NPT405 Cell line NCI-H226 Homo sapiens GI50 n.a. 23388.37 nM PubChem BioAssay data set
NPT170 Cell line SK-MEL-28 Homo sapiens GI50 n.a. 34276.78 nM PubChem BioAssay data set
NPT406 Cell line RXF 393 Homo sapiens GI50 n.a. 18749.95 nM PubChem BioAssay data set
NPT407 Cell line COLO 205 Homo sapiens GI50 n.a. 28183.83 nM PubChem BioAssay data set

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 NPC168059 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
0.75 Intermediate Similarity NPC229442
0.64 Remote Similarity NPC74821
0.5714 Remote Similarity NPC134360

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC168059 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
0.64 Remote Similarity NPD1548 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