Natural Product: NPC527364

Natural Product IDNPC527364
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (2~{R},3~{R})-3,5,7-trihydroxy-2-[4-hydroxy-3-[(2~{S},3~{R},4~{R},5~{S},6~{R})-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]oxy-phenyl]chroman-4-one
IUPAC Name (2~{R},3~{R})-3,5,7-trihydroxy-2-[4-hydroxy-3-[(2~{S},3~{R},4~{R},5~{S},6~{R})-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]oxy-phenyl]chroman-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 CZOXIGOPZRIBJM-SQTKABDHSA-N
Standard InCHI InChI=1S/C21H22O12/c22-6-13-15(26)17(28)19(30)21(33-13)32-11-3-7(1-2-9(11)24)20-18(29)16(27)14-10(25)4-8(23)5-12(14)31-20/h1-5,13,15,17-26,28-30H,6H2/t13-,15-,17-,18+,19-,20-,21-/m1/s1
SMILES O=C1C2=C(O)C=C(O)C=C2O[C@H](C2=CC=C(O)C(O[C@@H]3O[C@H](CO)[C@@H](O)[C@@H](O)[C@H]3O)=C2)[C@H]1O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   466.11 Volume:   424.574
?
Van der Waals volume.
Dense:   1.098 LogP:   -0.291
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   0.507
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.612
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   24.0
TPSA:   206.6
?
Topological Polar Surface Area.
 H-Bond Acceptor:   12.0
H-Bond Donor:   8.0 Rings:   4.0
Heavy Atoms:   12.0

MedChem Properties

QED Drug-Likeness Score:   0.263 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.301 Fsp3:   0.381
MCE-18:   94.034
?
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:   1
Chelating Alert:   1 PAINS Alert:   0
Colloidal aggregators:   0.598 Fluc inhibitor:   0.368
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.078
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.325
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.406 Promiscuous compounds:   0.485

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.645 MDCK Permeability:   -4.961
Pgp-inhibitor:   0.0 Pgp-substrate:   0.573
PAMPA:   0.997
?
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):   0.374
20% Bioavailability (F20%):   0.26 30% Bioavailability (F30%):   0.996
50% Bioavailability (F50%):   0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.402
Plasma Protein Binding (PPB):   87.879% Volume Distribution (VD):   -0.097
Fu: 11.888%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.463
BSEP inhibitor:   0.002

ADMET: Metabolism

CYP1A2-inhibitor:   0.044 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.033 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.01
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.982
HLM stability:   0.001
?
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):  4.136 Half-life (T1/2):  4.362

ADMET: Toxicity

hERG Blockers:  0.019 hERG Blockers (10um):  0.134
Human Hepatotoxicity (H-HT):  0.556 Drug-induced Liver Injury (DILI):  0.426
AMES Toxicity:  0.815 Rat Oral Acute Toxicity:  0.026
Maximum Recommended Daily Dose:  0.064 Skin Sensitization:  0.989
Carcinogencity:  0.081 Eye Corrosion:  0.0
Eye Irritation:  0.197 Respiratory Toxicity:  0.032
Drug-induced Neurotoxicity:  0.003 Ototoxicity:  0.963
Hematotoxicity:  0.169 Drug-induced Nephrotoxicity:  0.484
Genotoxicity:  0.845 RPMI-8226 Immunitoxicity:  0.152
A549 Cytotoxicity:  0.266 Hek293 Cytotoxicity:  0.474
BCF:   0.378
?
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:   2.808
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.208
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.501
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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
NPO7591 Cedrus deodara Species Pinaceae Eukaryota n.a. n.a. n.a. PMID[23387901]
NPO20918 Pseudotsuga menziesii Species Pinaceae Eukaryota n.a. n.a. n.a. PMID[34216094]
NPO16414 Thuja plicata Species Cupressaceae Eukaryota n.a. n.a. n.a. PMID[36985451]
NPO16414 Thuja plicata Species Cupressaceae Eukaryota n.a. n.a. n.a. PMID[38794396]
NPO63215 Pinus slyvestris Genus Pinaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO31384 Thuja orientalis Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20918 Pseudotsuga menziesii Species Pinaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16414 Thuja plicata Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2741 Ribes sanguineum Species Grossulariaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19614 Erica cinerea Species Ericaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7591 Cedrus deodara Species Pinaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO695 Picea sitchensis Species Pinaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19614 Erica cinerea Species Ericaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO31384 Thuja orientalis Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO695 Picea sitchensis Species Pinaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO16414 Thuja plicata Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO7591 Cedrus deodara Species Pinaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO16414 Thuja plicata Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO695 Picea sitchensis Species Pinaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO19614 Erica cinerea Species Ericaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO7591 Cedrus deodara Species Pinaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO7591 Cedrus deodara Species Pinaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO31384 Thuja orientalis Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO16414 Thuja plicata Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20918 Pseudotsuga menziesii Species Pinaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO695 Picea sitchensis Species Pinaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2741 Ribes sanguineum Species Grossulariaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7591 Cedrus deodara Species Pinaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19614 Erica cinerea Species Ericaceae 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 NPC527364 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
0.7121 Intermediate Similarity NPC326037
0.7121 Intermediate Similarity NPC13858
0.641 Remote Similarity NPC36916
0.641 Remote Similarity NPC36
0.641 Remote Similarity NPC7154
0.641 Remote Similarity NPC125039
0.641 Remote Similarity NPC7688
0.6329 Remote Similarity NPC138688
0.6329 Remote Similarity NPC72787
0.6329 Remote Similarity NPC217795
0.6329 Remote Similarity NPC58223
0.6316 Remote Similarity NPC163191
0.6026 Remote Similarity NPC26195
0.5949 Remote Similarity NPC606364
0.589 Remote Similarity NPC477240
0.5857 Remote Similarity NPC205054
0.5854 Remote Similarity NPC279209
0.5854 Remote Similarity NPC102277
0.5854 Remote Similarity NPC479117
0.5854 Remote Similarity NPC236934
0.5833 Remote Similarity NPC106025
0.5821 Remote Similarity NPC62290
0.5821 Remote Similarity NPC142731
0.5821 Remote Similarity NPC326506
0.5769 Remote Similarity NPC160156
0.5769 Remote Similarity NPC92565
0.5696 Remote Similarity NPC88484
0.5676 Remote Similarity NPC199335
0.56 Remote Similarity NPC190217
0.5595 Remote Similarity NPC259834
0.5571 Remote Similarity NPC36835
0.5571 Remote Similarity NPC246162
0.5571 Remote Similarity NPC9743
0.5571 Remote Similarity NPC260491
0.5571 Remote Similarity NPC61506
0.5571 Remote Similarity NPC240476
0.55 Remote Similarity NPC259182
0.5495 Remote Similarity NPC168789
0.5417 Remote Similarity NPC320825
0.5417 Remote Similarity NPC52530
0.5395 Remote Similarity NPC469661
0.5395 Remote Similarity NPC65530
0.5366 Remote Similarity NPC257963
0.5362 Remote Similarity NPC4152
0.5342 Remote Similarity NPC210015
0.5301 Remote Similarity NPC181014
0.5294 Remote Similarity NPC469586
0.5244 Remote Similarity NPC51328
0.5244 Remote Similarity NPC39351
0.5244 Remote Similarity NPC55158
0.5217 Remote Similarity NPC21835
0.5211 Remote Similarity NPC44721
0.5211 Remote Similarity NPC211466
0.5211 Remote Similarity NPC605332
0.5185 Remote Similarity NPC169248
0.5185 Remote Similarity NPC72649
0.5181 Remote Similarity NPC38041
0.5181 Remote Similarity NPC18979
0.5181 Remote Similarity NPC22150
0.5143 Remote Similarity NPC279417
0.5143 Remote Similarity NPC208176
0.5143 Remote Similarity NPC49130
0.5139 Remote Similarity NPC250922
0.507 Remote Similarity NPC19721

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC527364 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
0.641 Remote Similarity NPD6166 Phase 2
0.641 Remote Similarity NPD6167 Clinical (unspecified phase)
0.641 Remote Similarity NPD6168 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