Natural Product: NPC498673

Natural Product IDNPC498673
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 5-hydroxy-6-methoxy-7-[(2~{S},3~{R},4~{S},5~{S},6~{R})-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]oxy-3-(3,4,5-trimethoxyphenyl)chromen-4-one
IUPAC Name 5-hydroxy-6-methoxy-7-[(2~{S},3~{R},4~{S},5~{S},6~{R})-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]oxy-3-(3,4,5-trimethoxyphenyl)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 XNLQXDUYCJUCEO-YZWUXRCDSA-N
Standard InCHI InChI=1S/C25H28O13/c1-32-13-5-10(6-14(33-2)23(13)34-3)11-9-36-12-7-15(24(35-4)20(29)17(12)18(11)27)37-25-22(31)21(30)19(28)16(8-26)38-25/h5-7,9,16,19,21-22,25-26,28-31H,8H2,1-4H3/t16-,19-,21+,22-,25-/m1/s1
SMILES COC1=CC(C2=COC3=CC(O[C@@H]4O[C@H](CO)[C@@H](O)[C@H](O)[C@H]4O)=C(OC)C(O)=C3C2=O)=CC(OC)=C1OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   536.15 Volume:   499.912
?
Van der Waals volume.
Dense:   1.072 LogP:   0.624
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.108
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.517
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The logarithm of aqueous solubility value.
Rotatable Bonds:   8.0 Rigid Bonds:   24.0
TPSA:   186.74
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Topological Polar Surface Area.
 H-Bond Acceptor:   13.0
H-Bond Donor:   5.0 Rings:   4.0
Heavy Atoms:   13.0

MedChem Properties

QED Drug-Likeness Score:   0.266 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.05 Fsp3:   0.4
MCE-18:   92.0
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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:   Accepted BMS Rule:   0
Chelating Alert:   1 PAINS Alert:   0
Colloidal aggregators:   0.422 Fluc inhibitor:   0.201
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.636
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.736
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.081 Promiscuous compounds:   0.558

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.029 MDCK Permeability:   -5.327
Pgp-inhibitor:   0.003 Pgp-substrate:   0.249
PAMPA:   0.91
?
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):   0.229
20% Bioavailability (F20%):   0.021 30% Bioavailability (F30%):   0.752
50% Bioavailability (F50%):   0.982

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.105 MRP1:   0.884
Plasma Protein Binding (PPB):   84.443% Volume Distribution (VD):   -0.26
Fu: 16.067%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.464
BSEP inhibitor:   0.021

ADMET: Metabolism

CYP1A2-inhibitor:   0.035 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.001 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.003 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.037 CYP3A4-substrate:   0.002
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.218
HLM stability:   0.023
?
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):  2.658 Half-life (T1/2):  3.182

ADMET: Toxicity

hERG Blockers:  0.036 hERG Blockers (10um):  0.147
Human Hepatotoxicity (H-HT):  0.746 Drug-induced Liver Injury (DILI):  0.976
AMES Toxicity:  0.813 Rat Oral Acute Toxicity:  0.05
Maximum Recommended Daily Dose:  0.098 Skin Sensitization:  0.964
Carcinogencity:  0.42 Eye Corrosion:  0.0
Eye Irritation:  0.07 Respiratory Toxicity:  0.04
Drug-induced Neurotoxicity:  0.043 Ototoxicity:  0.928
Hematotoxicity:  0.467 Drug-induced Nephrotoxicity:  0.72
Genotoxicity:  0.638 RPMI-8226 Immunitoxicity:  0.231
A549 Cytotoxicity:  0.369 Hek293 Cytotoxicity:  0.321
BCF:   0.381
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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:   3.04
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.383
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.631
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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
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]
NPO7478 Iris germanica Species Iridaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7478 Iris germanica Species Iridaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO7478 Iris germanica Species Iridaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO7478 Iris germanica Species Iridaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]

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 NPC498673 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
0.8592 High Similarity NPC224462
0.8451 Intermediate Similarity NPC205076
0.8243 Intermediate Similarity NPC48773
0.8108 Intermediate Similarity NPC307518
0.76 Intermediate Similarity NPC481043
0.6883 Remote Similarity NPC73511
0.6538 Remote Similarity NPC105511
0.6329 Remote Similarity NPC197896
0.6329 Remote Similarity NPC313163
0.6282 Remote Similarity NPC135345
0.618 Remote Similarity NPC257714
0.6125 Remote Similarity NPC156457
0.6076 Remote Similarity NPC45165
0.6049 Remote Similarity NPC186807
0.6049 Remote Similarity NPC603655
0.6024 Remote Similarity NPC229729
0.5976 Remote Similarity NPC100720
0.5926 Remote Similarity NPC161749
0.5926 Remote Similarity NPC234739
0.5904 Remote Similarity NPC609451
0.5882 Remote Similarity NPC479407
0.5854 Remote Similarity NPC105025
0.5833 Remote Similarity NPC21666
0.5802 Remote Similarity NPC58053
0.5783 Remote Similarity NPC117260
0.5783 Remote Similarity NPC201292
0.5765 Remote Similarity NPC602805
0.5765 Remote Similarity NPC607201
0.5732 Remote Similarity NPC258035
0.5714 Remote Similarity NPC80140
0.5714 Remote Similarity NPC488071
0.5698 Remote Similarity NPC488072
0.5647 Remote Similarity NPC601607
0.5529 Remote Similarity NPC479402
0.5488 Remote Similarity NPC160515
0.5476 Remote Similarity NPC24043
0.5465 Remote Similarity NPC605067
0.5422 Remote Similarity NPC259070
0.5417 Remote Similarity NPC216769
0.5412 Remote Similarity NPC138540
0.5402 Remote Similarity NPC479406
0.5385 Remote Similarity NPC479405
0.5357 Remote Similarity NPC93337
0.5357 Remote Similarity NPC603782
0.5349 Remote Similarity NPC479401
0.5326 Remote Similarity NPC479404
0.5294 Remote Similarity NPC45638
0.5238 Remote Similarity NPC348541
0.5059 Remote Similarity NPC110349
0.5056 Remote Similarity NPC607707
0.5055 Remote Similarity NPC487212

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC498673 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
0.5926 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