Natural Product: NPC520103

Natural Product IDNPC520103
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 5-hydroxy-7-methoxy-3-[4-[(2~{S},3~{R},4~{S},5~{R},6~{S})-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]oxyphenyl]chromen-4-one
IUPAC Name 5-hydroxy-7-methoxy-3-[4-[(2~{S},3~{R},4~{S},5~{R},6~{S})-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 OFUWGCQDMVDLIR-XXGVUKKKSA-N
Standard InCHI InChI=1S/C22H22O10/c1-29-12-6-14(24)17-15(7-12)30-9-13(18(17)25)10-2-4-11(5-3-10)31-22-21(28)20(27)19(26)16(8-23)32-22/h2-7,9,16,19-24,26-28H,8H2,1H3/t16-,19-,20-,21+,22+/m0/s1
SMILES COC1=CC(O)=C2C(=O)C(C3=CC=C(O[C@@H]4O[C@@H](CO)[C@H](O)[C@H](O)[C@H]4O)C=C3)=COC2=C1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   446.12 Volume:   421.653
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Van der Waals volume.
Dense:   1.058 LogP:   1.18
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.741
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.174
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The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   24.0
TPSA:   159.05
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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:   0.37 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.761 Fsp3:   0.318
MCE-18:   83.621
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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:   0.569 Fluc inhibitor:   0.465
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.889
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.781
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.104 Promiscuous compounds:   0.314

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.328 MDCK Permeability:   -5.405
Pgp-inhibitor:   0.003 Pgp-substrate:   0.227
PAMPA:   0.951
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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):   0.938
20% Bioavailability (F20%):   0.375 30% Bioavailability (F30%):   0.958
50% Bioavailability (F50%):   0.982

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.023 MRP1:   0.088
Plasma Protein Binding (PPB):   90.176% Volume Distribution (VD):   -0.133
Fu: 8.875%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.997
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.757
BSEP inhibitor:   0.036

ADMET: Metabolism

CYP1A2-inhibitor:   0.02 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.033 CYP2C9-substrate:   0.001
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.039
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.399
HLM stability:   0.0
?
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):  2.556 Half-life (T1/2):  1.86

ADMET: Toxicity

hERG Blockers:  0.047 hERG Blockers (10um):  0.205
Human Hepatotoxicity (H-HT):  0.756 Drug-induced Liver Injury (DILI):  0.995
AMES Toxicity:  0.945 Rat Oral Acute Toxicity:  0.185
Maximum Recommended Daily Dose:  0.076 Skin Sensitization:  0.951
Carcinogencity:  0.453 Eye Corrosion:  0.0
Eye Irritation:  0.461 Respiratory Toxicity:  0.126
Drug-induced Neurotoxicity:  0.037 Ototoxicity:  0.826
Hematotoxicity:  0.492 Drug-induced Nephrotoxicity:  0.855
Genotoxicity:  0.909 RPMI-8226 Immunitoxicity:  0.187
A549 Cytotoxicity:  0.541 Hek293 Cytotoxicity:  0.248
BCF:   0.65
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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:   3.43
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.909
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.169
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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
NPO24343 Dalbergia spinosa Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24343 Dalbergia spinosa Species Fabaceae 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 NPC520103 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
1.0 High Similarity NPC73511
0.8194 Intermediate Similarity NPC197896
0.8194 Intermediate Similarity NPC313163
0.7945 Intermediate Similarity NPC234739
0.7917 Intermediate Similarity NPC160515
0.7703 Intermediate Similarity NPC156457
0.72 Intermediate Similarity NPC45165
0.7179 Intermediate Similarity NPC80140
0.716 Intermediate Similarity NPC487212
0.7108 Intermediate Similarity NPC479405
0.7051 Intermediate Similarity NPC205076
0.7024 Intermediate Similarity NPC479404
0.7 Intermediate Similarity NPC307518
0.6974 Remote Similarity NPC135345
0.6883 Remote Similarity NPC348541
0.6795 Remote Similarity NPC258035
0.6716 Remote Similarity NPC116632
0.6667 Remote Similarity NPC229729
0.6625 Remote Similarity NPC100720
0.6625 Remote Similarity NPC138540
0.6582 Remote Similarity NPC487213
0.6582 Remote Similarity NPC161749
0.6543 Remote Similarity NPC224462
0.6543 Remote Similarity NPC479402
0.6506 Remote Similarity NPC48773
0.6375 Remote Similarity NPC105511
0.6375 Remote Similarity NPC95090
0.6375 Remote Similarity NPC27408
0.6341 Remote Similarity NPC481043
0.6292 Remote Similarity NPC479403
0.625 Remote Similarity NPC289667
0.6173 Remote Similarity NPC603782
0.6145 Remote Similarity NPC479401
0.6136 Remote Similarity NPC303913
0.6118 Remote Similarity NPC479407
0.6071 Remote Similarity NPC486578
0.6 Remote Similarity NPC607707
0.5949 Remote Similarity NPC25547
0.5915 Remote Similarity NPC303644
0.5882 Remote Similarity NPC22832
0.5882 Remote Similarity NPC243930
0.5882 Remote Similarity NPC601607
0.5844 Remote Similarity NPC249824
0.5814 Remote Similarity NPC479406
0.5765 Remote Similarity NPC285197
0.5714 Remote Similarity NPC22195
0.5714 Remote Similarity NPC84362
0.5714 Remote Similarity NPC21190
0.5663 Remote Similarity NPC58053
0.5647 Remote Similarity NPC60966
0.5641 Remote Similarity NPC133400
0.5595 Remote Similarity NPC277205
0.5595 Remote Similarity NPC37919
0.5595 Remote Similarity NPC323593
0.5595 Remote Similarity NPC203500
0.557 Remote Similarity NPC191154
0.5568 Remote Similarity NPC267254
0.5568 Remote Similarity NPC601586
0.5529 Remote Similarity NPC186807
0.5517 Remote Similarity NPC610187
0.55 Remote Similarity NPC134819
0.5476 Remote Similarity NPC39360
0.5476 Remote Similarity NPC29763
0.5476 Remote Similarity NPC211014
0.5476 Remote Similarity NPC210003
0.5455 Remote Similarity NPC311830
0.5455 Remote Similarity NPC607201
0.5412 Remote Similarity NPC297987
0.5412 Remote Similarity NPC136042
0.5412 Remote Similarity NPC189142
0.5412 Remote Similarity NPC77660
0.5402 Remote Similarity NPC307938
0.5395 Remote Similarity NPC114192
0.5385 Remote Similarity NPC203636
0.5306 Remote Similarity NPC135358
0.5294 Remote Similarity NPC259070
0.5294 Remote Similarity NPC261866
0.5294 Remote Similarity NPC143851
0.5287 Remote Similarity NPC472459
0.5275 Remote Similarity NPC251417
0.5233 Remote Similarity NPC64305
0.5204 Remote Similarity NPC235575
0.5172 Remote Similarity NPC181712
0.5169 Remote Similarity NPC148710
0.5169 Remote Similarity NPC601144
0.5146 Remote Similarity NPC277532
0.5116 Remote Similarity NPC44558
0.5111 Remote Similarity NPC116458
0.5111 Remote Similarity NPC246943
0.5111 Remote Similarity NPC605784
0.5106 Remote Similarity NPC475155
0.5067 Remote Similarity NPC294409
0.5067 Remote Similarity NPC490701
0.5065 Remote Similarity NPC90665
0.506 Remote Similarity NPC488570
0.5056 Remote Similarity NPC609451
0.5053 Remote Similarity NPC131745
0.5052 Remote Similarity NPC51326
0.5052 Remote Similarity NPC257714

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC520103 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
0.6582 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