Natural Product: NPC572364

Natural Product IDNPC572364
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 9-hydroxy-7-[4-[(2~{R},3~{S},4~{R},5~{R},6~{S})-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]oxyphenyl]-[1,3]dioxolo[4,5-g]chromen-8-one
IUPAC Name 9-hydroxy-7-[4-[(2~{R},3~{S},4~{R},5~{R},6~{S})-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]oxyphenyl]-[1,3]dioxolo[4,5-g]chromen-8-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 SWSLNGRJTHYWLO-XIWOVWKKSA-N
Standard InCHI InChI=1S/C22H20O11/c23-6-14-17(25)19(27)20(28)22(33-14)32-10-3-1-9(2-4-10)11-7-29-12-5-13-21(31-8-30-13)18(26)15(12)16(11)24/h1-5,7,14,17,19-20,22-23,25-28H,6,8H2/t14-,17-,19+,20-,22-/m0/s1
SMILES O=C1C(C2=CC=C(O[C@H]3O[C@@H](CO)[C@H](O)[C@@H](O)[C@@H]3O)C=C2)=COC2=CC3=C(OCO3)C(O)=C12

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   460.1 Volume:   421.887
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Van der Waals volume.
Dense:   1.091 LogP:   0.539
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.334
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.305
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The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   28.0
TPSA:   168.28
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Topological Polar Surface Area.
 H-Bond Acceptor:   11.0
H-Bond Donor:   5.0 Rings:   5.0
Heavy Atoms:   11.0

MedChem Properties

QED Drug-Likeness Score:   0.357 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.016 Fsp3:   0.318
MCE-18:   99.0
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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:   1 PAINS Alert:   0
Colloidal aggregators:   0.696 Fluc inhibitor:   0.381
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.862
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.689
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.051 Promiscuous compounds:   0.218

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.383 MDCK Permeability:   -5.372
Pgp-inhibitor:   0.001 Pgp-substrate:   0.153
PAMPA:   0.995
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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):   0.885
20% Bioavailability (F20%):   0.254 30% Bioavailability (F30%):   0.758
50% Bioavailability (F50%):   0.911

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.266 MRP1:   0.088
Plasma Protein Binding (PPB):   90.493% Volume Distribution (VD):   -0.027
Fu: 8.232%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.982
OATP1B3 inhibitor:   0.991 BCRP inhibitor:   0.145
BSEP inhibitor:   0.274

ADMET: Metabolism

CYP1A2-inhibitor:   0.26 CYP1A2-substrate:   0.022
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.001
CYP2C9-inhibitor:   0.312 CYP2C9-substrate:   0.685
CYP2D6-inhibitor:   0.012 CYP2D6-substrate:   0.012
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.999
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.362
HLM stability:   0.007
?
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):  1.817 Half-life (T1/2):  2.129

ADMET: Toxicity

hERG Blockers:  0.062 hERG Blockers (10um):  0.242
Human Hepatotoxicity (H-HT):  0.637 Drug-induced Liver Injury (DILI):  0.984
AMES Toxicity:  0.869 Rat Oral Acute Toxicity:  0.123
Maximum Recommended Daily Dose:  0.089 Skin Sensitization:  0.708
Carcinogencity:  0.354 Eye Corrosion:  0.0
Eye Irritation:  0.213 Respiratory Toxicity:  0.047
Drug-induced Neurotoxicity:  0.034 Ototoxicity:  0.849
Hematotoxicity:  0.254 Drug-induced Nephrotoxicity:  0.911
Genotoxicity:  0.728 RPMI-8226 Immunitoxicity:  0.265
A549 Cytotoxicity:  0.388 Hek293 Cytotoxicity:  0.224
BCF:   0.759
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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:   3.421
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.108
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.225
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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
NPO22104 Trifolium pratense Species Fabaceae Eukaryota n.a. n.a. n.a. DOI[10.1016/S0031-9422(00)94679-X]
NPO7478 Iris germanica Species Iridaceae Eukaryota n.a. n.a. n.a. PMID[19299148]
NPO7478 Iris germanica Species Iridaceae Eukaryota n.a. rhizome n.a. PMID[22388969]
NPO7478 Iris germanica Species Iridaceae Eukaryota n.a. rhizome n.a. PMID[25204177]
NPO22104 Trifolium pratense Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[30199256]
NPO22104 Trifolium pratense Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7478 Iris germanica Species Iridaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO22104 Trifolium pratense Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO7478 Iris germanica Species Iridaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO22104 Trifolium pratense Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO7478 Iris germanica Species Iridaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO22104 Trifolium pratense Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO7478 Iris germanica Species Iridaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO22104 Trifolium pratense 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 NPC572364 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
0.7342 Intermediate Similarity NPC205076
0.7284 Intermediate Similarity NPC307518
0.7215 Intermediate Similarity NPC73511
0.6875 Remote Similarity NPC156457
0.6829 Remote Similarity NPC224462
0.6786 Remote Similarity NPC48773
0.6747 Remote Similarity NPC601607
0.6463 Remote Similarity NPC197896
0.6463 Remote Similarity NPC258035
0.6463 Remote Similarity NPC313163
0.642 Remote Similarity NPC45165
0.642 Remote Similarity NPC135345
0.6265 Remote Similarity NPC161749
0.6265 Remote Similarity NPC234739
0.622 Remote Similarity NPC160515
0.6133 Remote Similarity NPC285973
0.5977 Remote Similarity NPC229729
0.5882 Remote Similarity NPC105511
0.5765 Remote Similarity NPC58053
0.5747 Remote Similarity NPC100720
0.5747 Remote Similarity NPC138540
0.5698 Remote Similarity NPC603782
0.5682 Remote Similarity NPC481043
0.5682 Remote Similarity NPC80140
0.5663 Remote Similarity NPC25547
0.5632 Remote Similarity NPC186807
0.5543 Remote Similarity NPC487212
0.5532 Remote Similarity NPC479405
0.5506 Remote Similarity NPC479402
0.5474 Remote Similarity NPC479404
0.5432 Remote Similarity NPC295009
0.5402 Remote Similarity NPC348541
0.5375 Remote Similarity NPC225624
0.5333 Remote Similarity NPC479401
0.5326 Remote Similarity NPC479407
0.5227 Remote Similarity NPC211014
0.5165 Remote Similarity NPC609451
0.5109 Remote Similarity NPC21666
0.5109 Remote Similarity NPC605067
0.5056 Remote Similarity NPC289667
0.5054 Remote Similarity NPC479406

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC572364 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
0.6265 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