Natural Product: NPC520527

Natural Product IDNPC520527
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 5,7-dihydroxy-6-methoxy-3-[4-[(2~{S},3~{R},4~{S},5~{S},6~{R})-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]oxyphenyl]chromen-4-one
IUPAC Name 5,7-dihydroxy-6-methoxy-3-[4-[(2~{S},3~{R},4~{S},5~{S},6~{R})-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]oxyphenyl]chromen-4-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]

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 YGSMFMGAQQQYBQ-UDEBZQQRSA-N
Standard InCHI InChI=1S/C22H22O11/c1-30-21-12(24)6-13-15(18(21)27)16(25)11(8-31-13)9-2-4-10(5-3-9)32-22-20(29)19(28)17(26)14(7-23)33-22/h2-6,8,14,17,19-20,22-24,26-29H,7H2,1H3/t14-,17-,19+,20-,22-/m1/s1
SMILES COC1=C(O)C=C2OC=C(C3=CC=C(O[C@@H]4O[C@H](CO)[C@@H](O)[C@H](O)[C@H]4O)C=C3)C(=O)C2=C1O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   462.12 Volume:   430.443
?
Van der Waals volume.
Dense:   1.074 LogP:   0.736
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.337
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.254
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The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   24.0
TPSA:   179.28
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Topological Polar Surface Area.
 H-Bond Acceptor:   11.0
H-Bond Donor:   6.0 Rings:   4.0
Heavy Atoms:   11.0

MedChem Properties

QED Drug-Likeness Score:   0.302 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.925 Fsp3:   0.318
MCE-18:   86.966
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Accepted
Pfizer Rule:   Rejected GSK Rule:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   1 PAINS Alert:   0
Colloidal aggregators:   0.559 Fluc inhibitor:   0.322
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.876
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.825
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.101 Promiscuous compounds:   0.374

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.286 MDCK Permeability:   -5.418
Pgp-inhibitor:   0.001 Pgp-substrate:   0.263
PAMPA:   0.963
?
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):   0.298
20% Bioavailability (F20%):   0.064 30% Bioavailability (F30%):   0.893
50% Bioavailability (F50%):   0.969

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.093 MRP1:   0.085
Plasma Protein Binding (PPB):   85.086% Volume Distribution (VD):   -0.332
Fu: 11.177%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   0.321
BSEP inhibitor:   0.006

ADMET: Metabolism

CYP1A2-inhibitor:   0.732 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.011 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.001
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.047
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.974
HLM stability:   0.005
?
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):  2.455 Half-life (T1/2):  2.973

ADMET: Toxicity

hERG Blockers:  0.049 hERG Blockers (10um):  0.133
Human Hepatotoxicity (H-HT):  0.746 Drug-induced Liver Injury (DILI):  0.987
AMES Toxicity:  0.911 Rat Oral Acute Toxicity:  0.072
Maximum Recommended Daily Dose:  0.059 Skin Sensitization:  0.974
Carcinogencity:  0.378 Eye Corrosion:  0.0
Eye Irritation:  0.238 Respiratory Toxicity:  0.045
Drug-induced Neurotoxicity:  0.019 Ototoxicity:  0.927
Hematotoxicity:  0.354 Drug-induced Nephrotoxicity:  0.779
Genotoxicity:  0.811 RPMI-8226 Immunitoxicity:  0.14
A549 Cytotoxicity:  0.416 Hek293 Cytotoxicity:  0.257
BCF:   0.396
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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:   3.118
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.479
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.683
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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
NPO30734 Belamcanda chinensis Species Iridaceae Eukaryota n.a. n.a. n.a. DOI[10.1007/s11240-020-01863-w]
NPO30734 Belamcanda chinensis Species Iridaceae Eukaryota rhizomes Thai n.a. PMID[15787436]
NPO30734 Belamcanda chinensis Species Iridaceae Eukaryota n.a. n.a. n.a. PMID[36265291]
NPO30734 Belamcanda chinensis Species Iridaceae Eukaryota n.a. n.a. n.a. PMID[9917289]
NPO15902 Iris spuria Species Iridaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO30734 Belamcanda chinensis Species Iridaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO54777 Iris carthaliniae Species Iridaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15877 Iris crocea Species Tarachodidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO30734 Belamcanda chinensis Species Iridaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO15902 Iris spuria Species Iridaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO30734 Belamcanda chinensis Species Iridaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO15902 Iris spuria Species Iridaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15877 Iris crocea Species Tarachodidae 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 NPC520527 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
0.7703 Intermediate Similarity NPC156457
0.76 Intermediate Similarity NPC73511
0.7215 Intermediate Similarity NPC307518
0.7051 Intermediate Similarity NPC205076
0.7013 Intermediate Similarity NPC258035
0.6753 Remote Similarity NPC45165
0.6753 Remote Similarity NPC135345
0.675 Remote Similarity NPC224462
0.6716 Remote Similarity NPC35763
0.6707 Remote Similarity NPC48773
0.6543 Remote Similarity NPC481043
0.6463 Remote Similarity NPC229729
0.642 Remote Similarity NPC138540
0.6375 Remote Similarity NPC197896
0.6375 Remote Similarity NPC313163
0.6375 Remote Similarity NPC603782
0.622 Remote Similarity NPC100720
0.6173 Remote Similarity NPC105511
0.6173 Remote Similarity NPC161749
0.6173 Remote Similarity NPC234739
0.6145 Remote Similarity NPC479401
0.6125 Remote Similarity NPC160515
0.5952 Remote Similarity NPC479402
0.593 Remote Similarity NPC479407
0.5833 Remote Similarity NPC209487
0.5814 Remote Similarity NPC607201
0.5775 Remote Similarity NPC269451
0.5714 Remote Similarity NPC488080
0.5714 Remote Similarity NPC169977
0.5663 Remote Similarity NPC58053
0.5647 Remote Similarity NPC42773
0.5647 Remote Similarity NPC45522
0.5625 Remote Similarity NPC183036
0.5618 Remote Similarity NPC487212
0.5581 Remote Similarity NPC80140
0.5556 Remote Similarity NPC25547
0.5529 Remote Similarity NPC186807
0.5517 Remote Similarity NPC101026
0.5517 Remote Similarity NPC488077
0.5517 Remote Similarity NPC601607
0.5479 Remote Similarity NPC245382
0.5455 Remote Similarity NPC479406
0.5435 Remote Similarity NPC479405
0.5376 Remote Similarity NPC479404
0.5294 Remote Similarity NPC348541
0.5294 Remote Similarity NPC143851
0.5287 Remote Similarity NPC472459
0.5233 Remote Similarity NPC64305
0.5233 Remote Similarity NPC95090
0.5233 Remote Similarity NPC27408
0.52 Remote Similarity NPC250557
0.52 Remote Similarity NPC605826
0.5169 Remote Similarity NPC21666
0.5169 Remote Similarity NPC486578
0.5169 Remote Similarity NPC605067
0.5119 Remote Similarity NPC34287
0.5116 Remote Similarity NPC289667
0.5116 Remote Similarity NPC259070
0.5116 Remote Similarity NPC211014
0.5067 Remote Similarity NPC124714
0.5067 Remote Similarity NPC294409
0.5067 Remote Similarity NPC490701
0.5057 Remote Similarity NPC487213
0.5056 Remote Similarity NPC609451

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC520527 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
0.6173 Remote Similarity NPD4381 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