Natural Product: NPC545987

Natural Product IDNPC545987
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-3-[4-[(2~{S},3~{S},4~{R},5~{R},6~{S})-3,4,5-trihydroxy-6-methyl-tetrahydropyran-2-yl]oxyphenyl]chromen-4-one
IUPAC Name 5,7-dihydroxy-3-[4-[(2~{S},3~{S},4~{R},5~{R},6~{S})-3,4,5-trihydroxy-6-methyl-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 ALDGJOZWDGSBIY-MXFNLVDXSA-N
Standard InCHI InChI=1S/C21H20O9/c1-9-17(24)19(26)20(27)21(29-9)30-12-4-2-10(3-5-12)13-8-28-15-7-11(22)6-14(23)16(15)18(13)25/h2-9,17,19-24,26-27H,1H3/t9-,17-,19+,20-,21-/m0/s1
SMILES C[C@@H]1O[C@@H](OC2=CC=C(C3=COC4=CC(O)=CC(O)=C4C3=O)C=C2)[C@@H](O)[C@H](O)[C@H]1O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   416.11 Volume:   395.567
?
Van der Waals volume.
Dense:   1.052 LogP:   1.265
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.433
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.53
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The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   24.0
TPSA:   149.82
?
Topological Polar Surface Area.
 H-Bond Acceptor:   9.0
H-Bond Donor:   5.0 Rings:   4.0
Heavy Atoms:   9.0

MedChem Properties

QED Drug-Likeness Score:   0.423 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.808 Fsp3:   0.286
MCE-18:   84.259
?
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:   0.58 Fluc inhibitor:   0.37
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.922
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.71
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.226 Promiscuous compounds:   0.431

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.174 MDCK Permeability:   -5.196
Pgp-inhibitor:   0.0 Pgp-substrate:   0.481
PAMPA:   0.982
?
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):   0.011
20% Bioavailability (F20%):   0.079 30% Bioavailability (F30%):   0.582
50% Bioavailability (F50%):   0.948

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.005 MRP1:   0.041
Plasma Protein Binding (PPB):   93.358% Volume Distribution (VD):   -0.251
Fu: 4.684%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.941
OATP1B3 inhibitor:   0.982 BCRP inhibitor:   0.713
BSEP inhibitor:   0.431

ADMET: Metabolism

CYP1A2-inhibitor:   0.989 CYP1A2-substrate:   0.036
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.045 CYP2C9-substrate:   0.76
CYP2D6-inhibitor:   0.03 CYP2D6-substrate:   0.302
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.984
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.068
?
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):  2.871 Half-life (T1/2):  3.653

ADMET: Toxicity

hERG Blockers:  0.119 hERG Blockers (10um):  0.479
Human Hepatotoxicity (H-HT):  0.418 Drug-induced Liver Injury (DILI):  0.956
AMES Toxicity:  0.832 Rat Oral Acute Toxicity:  0.217
Maximum Recommended Daily Dose:  0.485 Skin Sensitization:  0.31
Carcinogencity:  0.22 Eye Corrosion:  0.0
Eye Irritation:  0.693 Respiratory Toxicity:  0.255
Drug-induced Neurotoxicity:  0.025 Ototoxicity:  0.833
Hematotoxicity:  0.067 Drug-induced Nephrotoxicity:  0.559
Genotoxicity:  0.961 RPMI-8226 Immunitoxicity:  0.124
A549 Cytotoxicity:  0.218 Hek293 Cytotoxicity:  0.483
BCF:   0.934
?
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:   3.675
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.659
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.245
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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
NPO10253 Pithecellobium dulce Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10253 Pithecellobium dulce 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 NPC545987 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
0.8429 Intermediate Similarity NPC156457
0.7887 Intermediate Similarity NPC160515
0.7067 Intermediate Similarity NPC348541
0.7013 Intermediate Similarity NPC138540
0.6914 Remote Similarity NPC487212
0.6757 Remote Similarity NPC25547
0.6567 Remote Similarity NPC294409
0.6567 Remote Similarity NPC490701
0.65 Remote Similarity NPC481043
0.6456 Remote Similarity NPC73511
0.6438 Remote Similarity NPC268668
0.641 Remote Similarity NPC211014
0.6329 Remote Similarity NPC258035
0.6 Remote Similarity NPC259070
0.5926 Remote Similarity NPC197896
0.5926 Remote Similarity NPC487213
0.5926 Remote Similarity NPC313163
0.5909 Remote Similarity NPC303913
0.5714 Remote Similarity NPC219904
0.5694 Remote Similarity NPC200316
0.5682 Remote Similarity NPC187379
0.5679 Remote Similarity NPC111929
0.5679 Remote Similarity NPC320283
0.5679 Remote Similarity NPC41121
0.5616 Remote Similarity NPC194653
0.561 Remote Similarity NPC127546
0.561 Remote Similarity NPC57625
0.561 Remote Similarity NPC173637
0.561 Remote Similarity NPC317489
0.561 Remote Similarity NPC223424
0.561 Remote Similarity NPC143851
0.561 Remote Similarity NPC600591
0.5542 Remote Similarity NPC64305
0.5542 Remote Similarity NPC234739
0.5488 Remote Similarity NPC135599
0.5488 Remote Similarity NPC73855
0.5488 Remote Similarity NPC113968
0.5488 Remote Similarity NPC328940
0.5488 Remote Similarity NPC277174
0.5488 Remote Similarity NPC606877
0.5467 Remote Similarity NPC104728
0.5441 Remote Similarity NPC39426
0.5441 Remote Similarity NPC608554
0.5412 Remote Similarity NPC205076
0.5405 Remote Similarity NPC279668
0.5405 Remote Similarity NPC278323
0.5357 Remote Similarity NPC161749
0.5357 Remote Similarity NPC265530
0.5349 Remote Similarity NPC479401
0.5349 Remote Similarity NPC80140
0.5316 Remote Similarity NPC78697
0.5316 Remote Similarity NPC233918
0.5309 Remote Similarity NPC107838
0.5301 Remote Similarity NPC45165
0.5301 Remote Similarity NPC135345
0.5278 Remote Similarity NPC78341
0.525 Remote Similarity NPC479305
0.5233 Remote Similarity NPC472459
0.5227 Remote Similarity NPC223747
0.5227 Remote Similarity NPC307518
0.5217 Remote Similarity NPC479405
0.5217 Remote Similarity NPC475155
0.5161 Remote Similarity NPC479404
0.5132 Remote Similarity NPC254702
0.5132 Remote Similarity NPC142876
0.5072 Remote Similarity NPC193792
0.507 Remote Similarity NPC38065
0.5057 Remote Similarity NPC100720

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC545987 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
0.5441 Remote Similarity NPD1510 Phase 2
0.5357 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