Natural Product: NPC18607

Natural Product IDNPC18607
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Chrysosplenol C
IUPAC Name 5,6-dihydroxy-2-(4-hydroxy-3-methoxyphenyl)-3,7-dimethoxychromen-4-one
Synonyms Chrysosplenol C
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL483031
PubChem CID 189065
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 QQBSPLCHDUCBNM-UHFFFAOYSA-N
Standard InCHI InChI=1S/C18H16O8/c1-23-10-6-8(4-5-9(10)19)17-18(25-3)16(22)13-11(26-17)7-12(24-2)14(20)15(13)21/h4-7,19-21H,1-3H3
SMILES COc1cc(ccc1O)c1oc2cc(OC)c(c(c2c(=O)c1OC)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   360.08 Volume:   343.445
?
Van der Waals volume.
Dense:   1.048 LogP:   1.993
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.021
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.868
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   18.0
TPSA:   118.59
?
Topological Polar Surface Area.
 H-Bond Acceptor:   8.0
H-Bond Donor:   3.0 Rings:   3.0
Heavy Atoms:   8.0

MedChem Properties

QED Drug-Likeness Score:   0.608 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.491 Fsp3:   0.167
MCE-18:   20.0
?
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:   0.395 Fluc inhibitor:   0.39
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.879
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.608
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.369 Promiscuous compounds:   0.812

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.183 MDCK Permeability:   -4.792
Pgp-inhibitor:   0.871 Pgp-substrate:   0.048
PAMPA:   0.153
?
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):   0.254
20% Bioavailability (F20%):   0.096 30% Bioavailability (F30%):   0.342
50% Bioavailability (F50%):   0.993

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.954
Plasma Protein Binding (PPB):   96.77% Volume Distribution (VD):   -0.556
Fu: 3.007%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.788
OATP1B3 inhibitor:   0.998 BCRP inhibitor:   0.997
BSEP inhibitor:   0.991

ADMET: Metabolism

CYP1A2-inhibitor:   0.541 CYP1A2-substrate:   0.008
CYP2C19-inhibitor:   0.007 CYP2C19-substrate:   0.492
CYP2C9-inhibitor:   0.069 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.78 CYP2D6-substrate:   0.665
CYP3A4-inhibitor:   0.001 CYP3A4-substrate:   0.012
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.981
HLM stability:   0.739
?
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):  6.511 Half-life (T1/2):  1.845

ADMET: Toxicity

hERG Blockers:  0.077 hERG Blockers (10um):  0.513
Human Hepatotoxicity (H-HT):  0.382 Drug-induced Liver Injury (DILI):  0.734
AMES Toxicity:  0.478 Rat Oral Acute Toxicity:  0.365
Maximum Recommended Daily Dose:  0.424 Skin Sensitization:  0.754
Carcinogencity:  0.708 Eye Corrosion:  0.366
Eye Irritation:  0.975 Respiratory Toxicity:  0.676
Drug-induced Neurotoxicity:  0.127 Ototoxicity:  0.198
Hematotoxicity:  0.198 Drug-induced Nephrotoxicity:  0.123
Genotoxicity:  0.409 RPMI-8226 Immunitoxicity:  0.076
A549 Cytotoxicity:  0.288 Hek293 Cytotoxicity:  0.369
BCF:   0.966
?
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:   3.517
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.355
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.91
?
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
NPO26589 Artemisia annua L. Strain Asteraceae Eukaryota n.a. n.a. n.a. PMID[ 21030913]
NPO26589 Artemisia annua L. Strain Asteraceae Eukaryota n.a. flower n.a. DOI[10.1007/s11418-006-0112-9]
NPO26589 Artemisia annua L. Strain Asteraceae Eukaryota n.a. stem n.a. DOI[10.1007/s11418-006-0112-9]
NPO26589 Artemisia annua L. Strain Asteraceae Eukaryota n.a. leaf n.a. DOI[10.1007/s11418-006-0112-9]
NPO20440 Chrysanthemum x morifolium Species Asteraceae Eukaryota Flowers n.a. n.a. DOI[10.1016/j.foodchem.2009.03.042]
NPO20440 Chrysanthemum x morifolium Species Asteraceae Eukaryota Flowers n.a. n.a. DOI[10.3136/fstr.15.499]
NPO20440 Chrysanthemum x morifolium Species Asteraceae Eukaryota Flowers n.a. n.a. DOI[10.5897/AJB10.140]
NPO20440 Chrysanthemum x morifolium Species Asteraceae Eukaryota Flowers n.a. n.a. DOI[10.5897/AJB2010.000-3252]
NPO20440 Chrysanthemum x morifolium Species Asteraceae Eukaryota Flowers Tongxiang, China n.a. PMID[24621197]
NPO30723 Inula aschersoniana Species Asteraceae Eukaryota n.a. aerial part n.a. PMID[25233586]
NPO28765 Miliusa balansae Species Annonaceae Eukaryota leaves n.a. n.a. PMID[26238320]
NPO20440 Chrysanthemum x morifolium Species Asteraceae Eukaryota Flowers n.a. n.a. PMID[28248102]
NPO26589 Artemisia annua L. Strain Asteraceae Eukaryota n.a. n.a. n.a. PMID[6387056]
NPO26589 Artemisia annua L. Strain Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10506 Artemisia apiacea Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20440 Chrysanthemum x morifolium Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10506 Artemisia apiacea Species Asteraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO26589 Artemisia annua L. Strain Asteraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO28765 Miliusa balansae Species Annonaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO28765 Miliusa balansae Species Annonaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO10506 Artemisia apiacea Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO20440 Chrysanthemum x morifolium Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO26589 Artemisia annua L. Strain Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO26589 Artemisia annua L. Strain Asteraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO10506 Artemisia apiacea Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO10506 Artemisia apiacea Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO20440 Chrysanthemum x morifolium Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO26589 Artemisia annua L. Strain Asteraceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO26589 Artemisia annua L. Strain Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10506 Artemisia apiacea Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20440 Chrysanthemum x morifolium Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28765 Miliusa balansae Species Annonaceae 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
NPT91 Cell line KB Homo sapiens ED50 = 11.2 ug ml-1 PMID[1955888]
NPT28438 Unchecked Unchecked n.a. IC50 n.a. n.a. n.a. PMID[35640148]
NPT28438 Unchecked Unchecked n.a. Inhibition n.a. n.a. % PMID[35640148]
NPT2 Others Unspecified n.a. Activity = 16.6 % PMID[26191362]
NPT2 Others Unspecified n.a. Activity = 53.0 % PMID[26191362]
NPT2 Others Unspecified n.a. Activity = 28.1 % PMID[26191362]

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 NPC18607 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
0.7778 Intermediate Similarity NPC305663
0.7407 Intermediate Similarity NPC43243
0.7368 Intermediate Similarity NPC261004
0.7368 Intermediate Similarity NPC78326
0.7321 Intermediate Similarity NPC300943
0.678 Remote Similarity NPC279989
0.661 Remote Similarity NPC179126
0.6441 Remote Similarity NPC253634
0.6333 Remote Similarity NPC288669
0.6333 Remote Similarity NPC236223
0.623 Remote Similarity NPC19687
0.623 Remote Similarity NPC152166
0.5833 Remote Similarity NPC198826
0.5738 Remote Similarity NPC162313
0.5574 Remote Similarity NPC214138
0.5574 Remote Similarity NPC146679
0.5574 Remote Similarity NPC188871
0.5574 Remote Similarity NPC101830
0.5556 Remote Similarity NPC58382
0.5556 Remote Similarity NPC128863
0.5484 Remote Similarity NPC18772
0.5469 Remote Similarity NPC252933
0.5469 Remote Similarity NPC47781
0.5469 Remote Similarity NPC137062
0.5429 Remote Similarity NPC174908
0.541 Remote Similarity NPC266960
0.541 Remote Similarity NPC275722
0.5397 Remote Similarity NPC176300
0.5397 Remote Similarity NPC270620
0.5397 Remote Similarity NPC212678
0.5385 Remote Similarity NPC227192
0.5323 Remote Similarity NPC57030
0.5323 Remote Similarity NPC163524
0.5323 Remote Similarity NPC610660
0.5312 Remote Similarity NPC25495
0.5312 Remote Similarity NPC236769
0.5312 Remote Similarity NPC283600
0.5246 Remote Similarity NPC607530
0.5231 Remote Similarity NPC606105
0.519 Remote Similarity NPC488072
0.5161 Remote Similarity NPC103904
0.5161 Remote Similarity NPC262094
0.5161 Remote Similarity NPC103342
0.5156 Remote Similarity NPC115798
0.5156 Remote Similarity NPC83508
0.5156 Remote Similarity NPC20830
0.5079 Remote Similarity NPC286342
0.5079 Remote Similarity NPC110070
0.5079 Remote Similarity NPC76376
0.5077 Remote Similarity NPC55619
0.5077 Remote Similarity NPC206604
0.5075 Remote Similarity NPC485299

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC18607 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