Natural Product: NPC505197

Natural Product IDNPC505197
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 5-hydroxy-2-(4-methoxyphenyl)-8,8-dimethyl-3-[(2~{S},3~{S},4~{R},5~{R},6~{S})-3,4,5-trihydroxy-6-methyl-tetrahydropyran-2-yl]oxy-pyrano[2,3-h]chromen-4-one
IUPAC Name 5-hydroxy-2-(4-methoxyphenyl)-8,8-dimethyl-3-[(2~{S},3~{S},4~{R},5~{R},6~{S})-3,4,5-trihydroxy-6-methyl-tetrahydropyran-2-yl]oxy-pyrano[2,3-h]chromen-4-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0001111] Flavonoid glycosides
          • [CHEMONTID:0001583] Flavonoid O-glycosides
            • [CHEMONTID:0003531] Flavonoid-3-O-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 HFACBAJBHOSYOZ-XXZNUWDDSA-N
Standard InCHI InChI=1S/C27H28O10/c1-12-19(29)21(31)22(32)26(34-12)36-25-20(30)18-16(28)11-17-15(9-10-27(2,3)37-17)24(18)35-23(25)13-5-7-14(33-4)8-6-13/h5-12,19,21-22,26,28-29,31-32H,1-4H3/t12-,19-,21+,22-,26-/m0/s1
SMILES COC1=CC=C(C2=C(O[C@@H]3O[C@@H](C)[C@H](O)[C@@H](O)[C@@H]3O)C(=O)C3=C(O)C=C4OC(C)(C)C=CC4=C3O2)C=C1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   512.17 Volume:   496.94
?
Van der Waals volume.
Dense:   1.031 LogP:   2.561
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.632
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.756
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   29.0
TPSA:   148.05
?
Topological Polar Surface Area.
 H-Bond Acceptor:   10.0
H-Bond Donor:   4.0 Rings:   5.0
Heavy Atoms:   10.0

MedChem Properties

QED Drug-Likeness Score:   0.411 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.245 Fsp3:   0.37
MCE-18:   109.703
?
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:   Accepted BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.709 Fluc inhibitor:   0.393
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.899
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.921
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.085 Promiscuous compounds:   0.197

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.827 MDCK Permeability:   -5.025
Pgp-inhibitor:   0.539 Pgp-substrate:   0.355
PAMPA:   0.941
?
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):   0.094
20% Bioavailability (F20%):   0.801 30% Bioavailability (F30%):   0.99
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.001 MRP1:   0.562
Plasma Protein Binding (PPB):   94.667% Volume Distribution (VD):   0.063
Fu: 4.749%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.997
OATP1B3 inhibitor:   0.989 BCRP inhibitor:   0.86
BSEP inhibitor:   0.994

ADMET: Metabolism

CYP1A2-inhibitor:   0.002 CYP1A2-substrate:   0.013
CYP2C19-inhibitor:   0.001 CYP2C19-substrate:   0.002
CYP2C9-inhibitor:   0.196 CYP2C9-substrate:   0.004
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.001
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.922
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.904
?
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):  2.243 Half-life (T1/2):  2.123

ADMET: Toxicity

hERG Blockers:  0.052 hERG Blockers (10um):  0.297
Human Hepatotoxicity (H-HT):  0.642 Drug-induced Liver Injury (DILI):  0.992
AMES Toxicity:  0.909 Rat Oral Acute Toxicity:  0.139
Maximum Recommended Daily Dose:  0.169 Skin Sensitization:  0.981
Carcinogencity:  0.443 Eye Corrosion:  0.0
Eye Irritation:  0.395 Respiratory Toxicity:  0.284
Drug-induced Neurotoxicity:  0.045 Ototoxicity:  0.654
Hematotoxicity:  0.35 Drug-induced Nephrotoxicity:  0.687
Genotoxicity:  0.596 RPMI-8226 Immunitoxicity:  0.258
A549 Cytotoxicity:  0.467 Hek293 Cytotoxicity:  0.417
BCF:   1.595
?
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:   4.195
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.729
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.16
?
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
NPO28569 Epimedium acuminatum Species Berberidaceae Eukaryota n.a. aerial part n.a. PMID[1442064]
NPO28569 Epimedium acuminatum Species Berberidaceae Eukaryota n.a. n.a. n.a. PMID[36300020]
NPO28569 Epimedium acuminatum Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28569 Epimedium acuminatum Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO28569 Epimedium acuminatum Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO28569 Epimedium acuminatum Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO28569 Epimedium acuminatum Species Berberidaceae 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

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 NPC505197 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
0.7174 Intermediate Similarity NPC5319
0.6484 Remote Similarity NPC278419
0.6484 Remote Similarity NPC179198
0.5934 Remote Similarity NPC611303
0.5889 Remote Similarity NPC46420
0.5714 Remote Similarity NPC271692
0.5667 Remote Similarity NPC249281
0.5652 Remote Similarity NPC59534
0.5604 Remote Similarity NPC158674
0.5543 Remote Similarity NPC349108
0.5495 Remote Similarity NPC289667
0.5484 Remote Similarity NPC472459
0.5474 Remote Similarity NPC116458
0.5474 Remote Similarity NPC246943
0.5464 Remote Similarity NPC251417
0.5426 Remote Similarity NPC219904
0.5417 Remote Similarity NPC66087
0.5361 Remote Similarity NPC265115
0.5312 Remote Similarity NPC605784
0.5258 Remote Similarity NPC276377
0.5258 Remote Similarity NPC355481
0.5253 Remote Similarity NPC480466
0.5248 Remote Similarity NPC131745
0.5243 Remote Similarity NPC72016
0.5243 Remote Similarity NPC606657
0.5217 Remote Similarity NPC111929
0.5217 Remote Similarity NPC320283
0.5217 Remote Similarity NPC41121
0.5152 Remote Similarity NPC480463
0.5106 Remote Similarity NPC64305
0.5106 Remote Similarity NPC265530
0.5053 Remote Similarity NPC305811
0.5053 Remote Similarity NPC27640
0.5052 Remote Similarity NPC148710

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC505197 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
0.7174 Intermediate Similarity NPD7804 Clinical (unspecified phase)

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