Natural Product: NPC259905

Natural Product IDNPC259905
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 5-Hydroxy-8-Methoxy-2-Methyl-6-[(2S,3R,4S,5S,6R)-3,4,5-Trihydroxy-6-(Hydroxymethyl)Oxan-2-Yl]Oxybenzo[G]Chromen-4-One
IUPAC Name 5-hydroxy-8-methoxy-2-methyl-6-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxybenzo[g]chromen-4-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL3634698
PubChem CID 3035617
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0001640] Naphthopyrans
        • [CHEMONTID:0001641] Naphthopyranones
          • [CHEMONTID:0001646] Naphthopyranone glycosides

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 CDMUGCVTTUOCFT-IAAKTDFRSA-N
Standard InCHI InChI=1S/C21H22O10/c1-8-3-11(23)16-12(29-8)5-9-4-10(28-2)6-13(15(9)18(16)25)30-21-20(27)19(26)17(24)14(7-22)31-21/h3-6,14,17,19-22,24-27H,7H2,1-2H3/t14-,17-,19+,20-,21-/m1/s1
SMILES Cc1cc(=O)c2c(cc3cc(cc(c3c2O)O[C@H]2[C@@H]([C@H]([C@@H]([C@@H](CO)O2)O)O)O)OC)o1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   434.12 Volume:   406.993
?
Van der Waals volume.
Dense:   1.067 LogP:   0.942
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.612
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.033
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   23.0
TPSA:   159.05
?
Topological Polar Surface Area.
 H-Bond Acceptor:   10.0
H-Bond Donor:   5.0 Rings:   4.0
Heavy Atoms:   10.0

MedChem Properties

QED Drug-Likeness Score:   0.358 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.016 Fsp3:   0.381
MCE-18:   86.966
?
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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.553 Fluc inhibitor:   0.024
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.585
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.725
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.075 Promiscuous compounds:   0.248

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.005 MDCK Permeability:   -5.217
Pgp-inhibitor:   0.002 Pgp-substrate:   0.102
PAMPA:   0.827
?
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):   0.042
20% Bioavailability (F20%):   0.056 30% Bioavailability (F30%):   0.773
50% Bioavailability (F50%):   0.88

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.015 MRP1:   0.767
Plasma Protein Binding (PPB):   85.677% Volume Distribution (VD):   -0.088
Fu: 13.209%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.011
BSEP inhibitor:   0.301

ADMET: Metabolism

CYP1A2-inhibitor:   0.69 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.002 CYP2C9-substrate:   0.001
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.293
HLM stability:   0.255
?
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):  2.346 Half-life (T1/2):  3.123

ADMET: Toxicity

hERG Blockers:  0.027 hERG Blockers (10um):  0.115
Human Hepatotoxicity (H-HT):  0.744 Drug-induced Liver Injury (DILI):  0.975
AMES Toxicity:  0.943 Rat Oral Acute Toxicity:  0.086
Maximum Recommended Daily Dose:  0.212 Skin Sensitization:  0.976
Carcinogencity:  0.519 Eye Corrosion:  0.0
Eye Irritation:  0.465 Respiratory Toxicity:  0.133
Drug-induced Neurotoxicity:  0.013 Ototoxicity:  0.86
Hematotoxicity:  0.373 Drug-induced Nephrotoxicity:  0.654
Genotoxicity:  0.919 RPMI-8226 Immunitoxicity:  0.159
A549 Cytotoxicity:  0.405 Hek293 Cytotoxicity:  0.343
BCF:   0.361
?
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:   3.025
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.359
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.648
?
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
NPO31136 Cassia tora Species Fabaceae Eukaryota seeds n.a. n.a. PMID[26483136]
NPO31136 Cassia tora Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO6675 Aplophyllum myrtifolium n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO559 Mimusops globosa Species Sapotaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4278 Wikstroemia monticola Species Thymelaeaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1671.1 Xanthium strumarium var. canadense Varieties Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO31136 Cassia tora Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO4278 Wikstroemia monticola Species Thymelaeaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO4278 Wikstroemia monticola Species Thymelaeaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO31136 Cassia tora Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO4278 Wikstroemia monticola Species Thymelaeaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO559 Mimusops globosa Species Sapotaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1671.1 Xanthium strumarium var. canadense Varieties Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6675 Aplophyllum myrtifolium n.a. n.a. n.a. 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
NPT862 Individual protein Epoxide hydratase Homo sapiens Inhibition = 38.1 % PMID[26483136]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference

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 NPC259905 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
0.8333 Intermediate Similarity NPC213052
0.6716 Remote Similarity NPC7025
0.64 Remote Similarity NPC191154
0.5823 Remote Similarity NPC38775
0.5783 Remote Similarity NPC199533
0.5769 Remote Similarity NPC94777
0.5488 Remote Similarity NPC26760
0.5435 Remote Similarity NPC63105
0.5432 Remote Similarity NPC189552
0.5357 Remote Similarity NPC183357
0.5341 Remote Similarity NPC108706
0.5309 Remote Similarity NPC134819
0.5205 Remote Similarity NPC100985
0.5135 Remote Similarity NPC123202
0.5067 Remote Similarity NPC7943
0.5059 Remote Similarity NPC611282

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC259905 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