Natural Product: NPC545399

Natural Product IDNPC545399
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 2-(3,4-dihydroxyphenyl)-5,6-dihydroxy-7-{[(2S,3R,4S,5R,6S)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy}-4H-chromen-4-one
IUPAC Name 2-(3,4-dihydroxyphenyl)-5,6-dihydroxy-7-[(2~{S},3~{R},4~{S},5~{R},6~{S})-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]oxy-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 HYPKUHLLPBGDLF-RJOPBHBASA-N
Standard InCHI InChI=1S/C21H20O12/c22-6-14-17(27)19(29)20(30)21(33-14)32-13-5-12-15(18(28)16(13)26)10(25)4-11(31-12)7-1-2-8(23)9(24)3-7/h1-5,14,17,19-24,26-30H,6H2/t14-,17-,19-,20+,21+/m0/s1
SMILES O=C1C=C(C2=CC=C(O)C(O)=C2)OC2=CC(O[C@@H]3O[C@@H](CO)[C@H](O)[C@H](O)[C@H]3O)=C(O)C(O)=C12

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   464.1 Volume:   421.937
?
Van der Waals volume.
Dense:   1.1 LogP:   0.742
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.231
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.335
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   24.0
TPSA:   210.51
?
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:   0.229 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.046 Fsp3:   0.286
MCE-18:   91.0
?
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:   0
Chelating Alert:   1 PAINS Alert:   1
Colloidal aggregators:   0.697 Fluc inhibitor:   0.311
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.968
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.805
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.307 Promiscuous compounds:   0.903

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.347 MDCK Permeability:   -4.959
Pgp-inhibitor:   0.0 Pgp-substrate:   0.079
PAMPA:   0.999
?
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):   0.936
20% Bioavailability (F20%):   0.992 30% Bioavailability (F30%):   1.0
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.001 MRP1:   0.854
Plasma Protein Binding (PPB):   82.947% Volume Distribution (VD):   -0.025
Fu: 14.943%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.995
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.925
BSEP inhibitor:   0.001

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.242
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):  4.213 Half-life (T1/2):  2.839

ADMET: Toxicity

hERG Blockers:  0.012 hERG Blockers (10um):  0.23
Human Hepatotoxicity (H-HT):  0.568 Drug-induced Liver Injury (DILI):  0.95
AMES Toxicity:  0.888 Rat Oral Acute Toxicity:  0.108
Maximum Recommended Daily Dose:  0.112 Skin Sensitization:  0.999
Carcinogencity:  0.239 Eye Corrosion:  0.0
Eye Irritation:  0.837 Respiratory Toxicity:  0.039
Drug-induced Neurotoxicity:  0.002 Ototoxicity:  0.81
Hematotoxicity:  0.134 Drug-induced Nephrotoxicity:  0.163
Genotoxicity:  0.97 RPMI-8226 Immunitoxicity:  0.054
A549 Cytotoxicity:  0.844 Hek293 Cytotoxicity:  0.288
BCF:   0.467
?
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:   3.023
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.629
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.867
?
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
NPO57110 Stereospermum suaveolens Species Bignoniaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]

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 NPC545399 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 NPC58716
0.8714 High Similarity NPC146792
0.831 Intermediate Similarity NPC45618
0.8205 Intermediate Similarity NPC3583
0.7838 Intermediate Similarity NPC245014
0.7703 Intermediate Similarity NPC189142
0.7703 Intermediate Similarity NPC77660
0.76 Intermediate Similarity NPC45638
0.75 Intermediate Similarity NPC201292
0.7013 Intermediate Similarity NPC168822
0.6923 Remote Similarity NPC84265
0.6706 Remote Similarity NPC607513
0.6667 Remote Similarity NPC39360
0.6667 Remote Similarity NPC29763
0.6667 Remote Similarity NPC210003
0.6667 Remote Similarity NPC601144
0.6667 Remote Similarity NPC605067
0.6582 Remote Similarity NPC93337
0.65 Remote Similarity NPC105025
0.6463 Remote Similarity NPC22832
0.6456 Remote Similarity NPC261866
0.6456 Remote Similarity NPC19709
0.6404 Remote Similarity NPC150767
0.6386 Remote Similarity NPC311830
0.6386 Remote Similarity NPC602805
0.6377 Remote Similarity NPC162313
0.6341 Remote Similarity NPC191306
0.631 Remote Similarity NPC469931
0.6265 Remote Similarity NPC601710
0.625 Remote Similarity NPC58053
0.6173 Remote Similarity NPC95090
0.6173 Remote Similarity NPC277205
0.6173 Remote Similarity NPC27408
0.6173 Remote Similarity NPC37919
0.6173 Remote Similarity NPC136042
0.6163 Remote Similarity NPC8856
0.6098 Remote Similarity NPC186807
0.6098 Remote Similarity NPC84362
0.6098 Remote Similarity NPC610763
0.6071 Remote Similarity NPC43211
0.6024 Remote Similarity NPC117260
0.5952 Remote Similarity NPC488071
0.5952 Remote Similarity NPC609451
0.593 Remote Similarity NPC190003
0.5882 Remote Similarity NPC243930
0.5854 Remote Similarity NPC83283
0.5854 Remote Similarity NPC143851
0.5814 Remote Similarity NPC605784
0.5814 Remote Similarity NPC607707
0.5795 Remote Similarity NPC254540
0.5783 Remote Similarity NPC145038
0.5783 Remote Similarity NPC56077
0.5783 Remote Similarity NPC281131
0.5783 Remote Similarity NPC253662
0.5783 Remote Similarity NPC179950
0.5783 Remote Similarity NPC88789
0.5783 Remote Similarity NPC259152
0.5783 Remote Similarity NPC491374
0.5765 Remote Similarity NPC237435
0.5714 Remote Similarity NPC115674
0.5647 Remote Similarity NPC42773
0.5647 Remote Similarity NPC45522
0.5604 Remote Similarity NPC210073
0.5595 Remote Similarity NPC282987
0.5595 Remote Similarity NPC297987
0.5595 Remote Similarity NPC609879
0.5591 Remote Similarity NPC65711
0.5542 Remote Similarity NPC473043
0.5542 Remote Similarity NPC331652
0.5517 Remote Similarity NPC115760
0.5465 Remote Similarity NPC599850
0.5455 Remote Similarity NPC88023
0.5455 Remote Similarity NPC309025
0.5444 Remote Similarity NPC606546
0.5417 Remote Similarity NPC256760
0.5412 Remote Similarity NPC323593
0.5412 Remote Similarity NPC203500
0.5402 Remote Similarity NPC285197
0.5393 Remote Similarity NPC601586
0.5368 Remote Similarity NPC229409
0.5349 Remote Similarity NPC24043
0.5342 Remote Similarity NPC198826
0.5341 Remote Similarity NPC284960
0.5341 Remote Similarity NPC486578
0.5333 Remote Similarity NPC477848
0.5294 Remote Similarity NPC289667
0.5294 Remote Similarity NPC77672
0.5294 Remote Similarity NPC133671
0.5294 Remote Similarity NPC135391
0.5294 Remote Similarity NPC78263
0.5294 Remote Similarity NPC250069
0.5287 Remote Similarity NPC222936
0.5287 Remote Similarity NPC27942
0.5281 Remote Similarity NPC116458
0.5281 Remote Similarity NPC246943
0.5275 Remote Similarity NPC472607
0.5263 Remote Similarity NPC470443
0.5253 Remote Similarity NPC603856
0.5227 Remote Similarity NPC20505
0.5222 Remote Similarity NPC488072
0.5217 Remote Similarity NPC603300
0.52 Remote Similarity NPC212678
0.5169 Remote Similarity NPC21666
0.5169 Remote Similarity NPC197285
0.5152 Remote Similarity NPC253685
0.5116 Remote Similarity NPC19388
0.5116 Remote Similarity NPC110349
0.5116 Remote Similarity NPC240431
0.5116 Remote Similarity NPC55786
0.5116 Remote Similarity NPC238376
0.5114 Remote Similarity NPC182045
0.5114 Remote Similarity NPC21100
0.5109 Remote Similarity NPC251417
0.5106 Remote Similarity NPC218488
0.5067 Remote Similarity NPC25270
0.5059 Remote Similarity NPC67037
0.5059 Remote Similarity NPC255615
0.5056 Remote Similarity NPC60735
0.5056 Remote Similarity NPC26230
0.5055 Remote Similarity NPC203050
0.5055 Remote Similarity NPC225434
0.5054 Remote Similarity NPC480466
0.5048 Remote Similarity NPC132111

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC545399 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
0.5765 Remote Similarity NPD4338 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