Natural Product: NPC212678

Natural Product IDNPC212678
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 5,6-Dihydroxy-2-(3-Hydroxy-4-Methoxyphenyl)-7-Methoxychromen-4-One
IUPAC Name 5,6-dihydroxy-2-(3-hydroxy-4-methoxyphenyl)-7-methoxychromen-4-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL77643
PubChem CID 373260
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0002585] O-methylated flavonoids
          • [CHEMONTID:0002592] 7-O-methylated flavonoids

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 GCKIPZDMMOATHU-UHFFFAOYSA-N
Standard InCHI InChI=1S/C17H14O7/c1-22-11-4-3-8(5-9(11)18)12-6-10(19)15-13(24-12)7-14(23-2)16(20)17(15)21/h3-7,18,20-21H,1-2H3
SMILES COc1ccc(cc1O)c1cc(=O)c2c(cc(c(c2O)O)OC)o1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   330.07 Volume:   317.359
?
Van der Waals volume.
Dense:   1.04 LogP:   2.209
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.158
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.247
?
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:   0.633 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.416 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:   1
Colloidal aggregators:   0.649 Fluc inhibitor:   0.887
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.915
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.701
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.474 Promiscuous compounds:   0.874

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.126 MDCK Permeability:   -4.791
Pgp-inhibitor:   0.293 Pgp-substrate:   0.117
PAMPA:   0.357
?
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):   0.235
20% Bioavailability (F20%):   0.55 30% Bioavailability (F30%):   0.828
50% Bioavailability (F50%):   0.993

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.001 MRP1:   0.978
Plasma Protein Binding (PPB):   96.422% Volume Distribution (VD):   -0.56
Fu: 4.021%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.997
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.996
BSEP inhibitor:   0.658

ADMET: Metabolism

CYP1A2-inhibitor:   0.125 CYP1A2-substrate:   0.052
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.003
CYP2C9-inhibitor:   0.782 CYP2C9-substrate:   0.004
CYP2D6-inhibitor:   0.955 CYP2D6-substrate:   0.282
CYP3A4-inhibitor:   0.003 CYP3A4-substrate:   0.053
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.977
HLM stability:   0.414
?
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):  4.58 Half-life (T1/2):  2.047

ADMET: Toxicity

hERG Blockers:  0.082 hERG Blockers (10um):  0.493
Human Hepatotoxicity (H-HT):  0.401 Drug-induced Liver Injury (DILI):  0.754
AMES Toxicity:  0.564 Rat Oral Acute Toxicity:  0.394
Maximum Recommended Daily Dose:  0.646 Skin Sensitization:  0.731
Carcinogencity:  0.694 Eye Corrosion:  0.378
Eye Irritation:  0.991 Respiratory Toxicity:  0.767
Drug-induced Neurotoxicity:  0.09 Ototoxicity:  0.156
Hematotoxicity:  0.169 Drug-induced Nephrotoxicity:  0.098
Genotoxicity:  0.686 RPMI-8226 Immunitoxicity:  0.08
A549 Cytotoxicity:  0.33 Hek293 Cytotoxicity:  0.448
BCF:   0.779
?
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:   3.401
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.512
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.992
?
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
NPO14027 Dacryodes normandii Species Burseraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO6388 Mulguraea tridens Species Verbenaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14201 Riccia fluitans Species Ricciaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14201 Riccia fluitans Species Ricciaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6388 Mulguraea tridens Species Verbenaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14027 Dacryodes normandii Species Burseraceae 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
NPT517 Cell line Panel NCI-60 (60 carcinoma cell lines) Homo sapiens GI50 > 100000.0 nM PMID[9632366]
NPT368 Cell line SN12C Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT370 Cell line NCI-H23 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT369 Cell line ACHN Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT371 Cell line UO-31 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT372 Cell line HOP-92 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT116 Cell line HL-60 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT374 Cell line SF-539 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT373 Cell line SK-MEL-5 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT375 Cell line Malme-3M Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT111 Cell line K562 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT376 Cell line A498 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT377 Cell line OVCAR-3 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT112 Cell line MOLT-4 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT379 Cell line HOP-62 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT380 Cell line U-251 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT381 Cell line OVCAR-8 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT382 Cell line OVCAR-5 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT383 Cell line SNB-19 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT572 Cell line DMS-273 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT385 Cell line SR Homo sapiens GI50 n.a. 44463.13 nM PubChem BioAssay data set
NPT384 Cell line TK-10 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT573 Cell line M19-MEL Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT323 Cell line SW-620 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT455 Cell line NCI-H522 Homo sapiens GI50 n.a. 53456.44 nM PubChem BioAssay data set
NPT386 Cell line KM12 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT387 Cell line M14 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT574 Cell line XF498 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT389 Cell line RPMI-8226 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT388 Cell line NCI-H322M Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT456 Cell line OVCAR-4 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT390 Cell line LOX IMVI Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT147 Cell line SK-MEL-2 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT575 Cell line KM-20L2 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT81 Cell line A549 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT392 Cell line SNB-75 Homo sapiens GI50 n.a. 31477.48 nM PubChem BioAssay data set
NPT391 Cell line HCC 2998 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT148 Cell line HCT-15 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT393 Cell line HCT-116 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT395 Cell line SF-268 Homo sapiens GI50 n.a. 84527.88 nM PubChem BioAssay data set
NPT394 Cell line EKVX Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT576 Cell line DMS-114 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT731 Cell line LXFL 529 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT146 Cell line SK-OV-3 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT398 Cell line UACC-62 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT397 Cell line NCI-H460 Homo sapiens GI50 n.a. 57942.87 nM PubChem BioAssay data set
NPT308 Cell line CAKI-1 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT458 Cell line IGROV-1 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT399 Cell line SF-295 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT577 Cell line RXF 631 Homo sapiens GI50 n.a. 92044.96 nM PubChem BioAssay data set
NPT401 Cell line 786-0 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT403 Cell line UACC-257 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT404 Cell line CCRF-CEM Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT579 Cell line DLD-1 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT405 Cell line NCI-H226 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT139 Cell line HT-29 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT170 Cell line SK-MEL-28 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT407 Cell line COLO 205 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT406 Cell line RXF 393 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT732 Cell line HOP-18 Homo sapiens GI50 n.a. 100000.0 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 NPC212678 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
0.8077 Intermediate Similarity NPC57030
0.7925 Intermediate Similarity NPC162313
0.7636 Intermediate Similarity NPC283600
0.7547 Intermediate Similarity NPC275722
0.7407 Intermediate Similarity NPC198826
0.7321 Intermediate Similarity NPC160951
0.7321 Intermediate Similarity NPC223579
0.7241 Intermediate Similarity NPC485299
0.7143 Intermediate Similarity NPC300943
0.6964 Remote Similarity NPC256283
0.6724 Remote Similarity NPC52005
0.6441 Remote Similarity NPC608258
0.6271 Remote Similarity NPC146165
0.6167 Remote Similarity NPC287101
0.6167 Remote Similarity NPC196439
0.6167 Remote Similarity NPC607642
0.5833 Remote Similarity NPC50715
0.5763 Remote Similarity NPC29353
0.5667 Remote Similarity NPC184136
0.5667 Remote Similarity NPC145379
0.5574 Remote Similarity NPC108406
0.5574 Remote Similarity NPC25270
0.5574 Remote Similarity NPC305663
0.55 Remote Similarity NPC43243
0.55 Remote Similarity NPC156222
0.5484 Remote Similarity NPC69394
0.5484 Remote Similarity NPC200740
0.5484 Remote Similarity NPC270620
0.541 Remote Similarity NPC100887
0.541 Remote Similarity NPC22519
0.541 Remote Similarity NPC604462
0.5397 Remote Similarity NPC25495
0.5397 Remote Similarity NPC93376
0.5397 Remote Similarity NPC177298
0.5397 Remote Similarity NPC18607
0.5397 Remote Similarity NPC195202
0.5395 Remote Similarity NPC22832
0.5323 Remote Similarity NPC603827
0.5312 Remote Similarity NPC47781
0.5312 Remote Similarity NPC137062
0.5246 Remote Similarity NPC127447
0.5246 Remote Similarity NPC239128
0.5238 Remote Similarity NPC255350
0.52 Remote Similarity NPC58716
0.5195 Remote Similarity NPC605067
0.5161 Remote Similarity NPC18260
0.5161 Remote Similarity NPC48479
0.5161 Remote Similarity NPC231772
0.5161 Remote Similarity NPC234133
0.5161 Remote Similarity NPC120163
0.5161 Remote Similarity NPC84515
0.5161 Remote Similarity NPC276409
0.5161 Remote Similarity NPC601901
0.5156 Remote Similarity NPC128863
0.5082 Remote Similarity NPC293183
0.5082 Remote Similarity NPC75279
0.5079 Remote Similarity NPC78913
0.5079 Remote Similarity NPC9609
0.5079 Remote Similarity NPC603662

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC212678 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
0.5238 Remote Similarity NPD2801 Pre-clinical

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