Natural Product: NPC545857

Natural Product IDNPC545857
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-dihydroxy-5-[(2~{S},3~{R},4~{R},5~{S},6~{R})-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]oxy-phenyl]-3,5,7-trihydroxy-chromen-4-one
IUPAC Name 2-[3,4-dihydroxy-5-[(2~{S},3~{R},4~{R},5~{S},6~{R})-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]oxy-phenyl]-3,5,7-trihydroxy-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 ZJYAVUPWMNHHEU-QPNURLTJSA-N
Standard InCHI InChI=1S/C21H20O13/c22-5-12-15(27)17(29)19(31)21(34-12)33-11-2-6(1-9(25)14(11)26)20-18(30)16(28)13-8(24)3-7(23)4-10(13)32-20/h1-4,12,15,17,19,21-27,29-31H,5H2/t12-,15-,17-,19-,21-/m1/s1
SMILES O=C1C(O)=C(C2=CC(O)=C(O)C(O[C@@H]3O[C@H](CO)[C@@H](O)[C@@H](O)[C@H]3O)=C2)OC2=CC(O)=CC(O)=C12

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   480.09 Volume:   430.728
?
Van der Waals volume.
Dense:   1.115 LogP:   0.294
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   0.936
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.676
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   24.0
TPSA:   230.74
?
Topological Polar Surface Area.
 H-Bond Acceptor:   13.0
H-Bond Donor:   9.0 Rings:   4.0
Heavy Atoms:   13.0

MedChem Properties

QED Drug-Likeness Score:   0.208 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.168 Fsp3:   0.286
MCE-18:   94.37
?
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:   1
Colloidal aggregators:   0.75 Fluc inhibitor:   0.227
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.876
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.701
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.327 Promiscuous compounds:   0.944

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.413 MDCK Permeability:   -4.898
Pgp-inhibitor:   0.0 Pgp-substrate:   0.142
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):   0.855
20% Bioavailability (F20%):   0.285 30% Bioavailability (F30%):   0.998
50% Bioavailability (F50%):   0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.175
Plasma Protein Binding (PPB):   84.644% Volume Distribution (VD):   -0.163
Fu: 11.846%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.98
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.973
BSEP inhibitor:   0.002

ADMET: Metabolism

CYP1A2-inhibitor:   0.019 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.079
CYP2C9-inhibitor:   0.003 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.001 CYP2D6-substrate:   0.058
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.812
?
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):  3.073 Half-life (T1/2):  4.349

ADMET: Toxicity

hERG Blockers:  0.015 hERG Blockers (10um):  0.147
Human Hepatotoxicity (H-HT):  0.51 Drug-induced Liver Injury (DILI):  0.645
AMES Toxicity:  0.742 Rat Oral Acute Toxicity:  0.047
Maximum Recommended Daily Dose:  0.133 Skin Sensitization:  0.986
Carcinogencity:  0.178 Eye Corrosion:  0.0
Eye Irritation:  0.736 Respiratory Toxicity:  0.022
Drug-induced Neurotoxicity:  0.001 Ototoxicity:  0.861
Hematotoxicity:  0.067 Drug-induced Nephrotoxicity:  0.053
Genotoxicity:  0.757 RPMI-8226 Immunitoxicity:  0.038
A549 Cytotoxicity:  0.258 Hek293 Cytotoxicity:  0.358
BCF:   0.439
?
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:   2.969
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.369
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.702
?
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
NPO1751 Ribes nigrum Species n.a. n.a. Fruit n.a. n.a. DOI[10.1016/S0963-9969(99)00095-2]
NPO1751 Ribes nigrum Species n.a. n.a. n.a. fruit n.a. PMID[16417304]
NPO4570 Myrtus communis Species Myrtaceae Eukaryota n.a. n.a. n.a. PMID[16499325]
NPO4570 Myrtus communis Species Myrtaceae Eukaryota leaves n.a. n.a. PMID[22276775]
NPO4570 Myrtus communis Species Myrtaceae Eukaryota n.a. n.a. n.a. PMID[35596201]
NPO1751 Ribes nigrum Species n.a. n.a. n.a. n.a. n.a. PMID[36557810]
NPO4570 Myrtus communis Species Myrtaceae Eukaryota n.a. n.a. n.a. PMID[38686775]
NPO8356 Hibiscus abelmoschus Species Malvaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1751 Ribes nigrum Species n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO4570 Myrtus communis Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20554 Astragalus complanatus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO45443 Thea sinensis Species Theaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7513.1 Cannabis sativa var. indica Varieties Cannabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1751 Ribes nigrum Species n.a. n.a. Fruits n.a. Database[FooDB]
NPO1751 Ribes nigrum Species n.a. n.a. Bulb n.a. n.a. Database[FooDB]
NPO1751 Ribes nigrum Species n.a. n.a. Seed Essent. Oil n.a. n.a. Database[FooDB]
NPO1751 Ribes nigrum Species n.a. n.a. Seed n.a. n.a. Database[FooDB]
NPO1751 Ribes nigrum Species n.a. n.a. Leaf n.a. n.a. Database[FooDB]
NPO1751 Ribes nigrum Species n.a. n.a. Fruit Juice n.a. n.a. Database[FooDB]
NPO1751 Ribes nigrum Species n.a. n.a. Fruit n.a. n.a. Database[FooDB]
NPO1751 Ribes nigrum Species n.a. n.a. n.a. n.a. Database[FooDB]
NPO20554 Astragalus complanatus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO7513.1 Cannabis sativa var. indica Varieties Cannabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO1751 Ribes nigrum Species n.a. n.a. n.a. n.a. n.a. Database[TCMID]
NPO20554 Astragalus complanatus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO7513.1 Cannabis sativa var. indica Varieties Cannabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO20554 Astragalus complanatus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO20554 Astragalus complanatus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO1751 Ribes nigrum Species n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO4570 Myrtus communis Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8356 Hibiscus abelmoschus Species Malvaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20554 Astragalus complanatus 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 NPC545857 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
0.7922 Intermediate Similarity NPC197285
0.7895 Intermediate Similarity NPC21100
0.7051 Intermediate Similarity NPC254306
0.6667 Remote Similarity NPC245014
0.6627 Remote Similarity NPC601710
0.6625 Remote Similarity NPC19388
0.6625 Remote Similarity NPC240431
0.6625 Remote Similarity NPC55786
0.6585 Remote Similarity NPC325555
0.6585 Remote Similarity NPC226304
0.6543 Remote Similarity NPC145038
0.6543 Remote Similarity NPC56077
0.6543 Remote Similarity NPC281131
0.6543 Remote Similarity NPC253662
0.6543 Remote Similarity NPC179950
0.6543 Remote Similarity NPC277205
0.6543 Remote Similarity NPC37919
0.6543 Remote Similarity NPC88789
0.6543 Remote Similarity NPC491374
0.6528 Remote Similarity NPC133953
0.6506 Remote Similarity NPC191306
0.6341 Remote Similarity NPC282987
0.631 Remote Similarity NPC60735
0.631 Remote Similarity NPC26230
0.631 Remote Similarity NPC285197
0.6279 Remote Similarity NPC203050
0.6279 Remote Similarity NPC225434
0.6279 Remote Similarity NPC601586
0.6265 Remote Similarity NPC84265
0.6235 Remote Similarity NPC486578
0.6235 Remote Similarity NPC609478
0.622 Remote Similarity NPC77672
0.622 Remote Similarity NPC133671
0.622 Remote Similarity NPC135391
0.622 Remote Similarity NPC78263
0.622 Remote Similarity NPC250069
0.622 Remote Similarity NPC143851
0.6163 Remote Similarity NPC88023
0.6163 Remote Similarity NPC136761
0.6163 Remote Similarity NPC309025
0.6145 Remote Similarity NPC64305
0.6145 Remote Similarity NPC323593
0.6145 Remote Similarity NPC203500
0.6145 Remote Similarity NPC609879
0.6047 Remote Similarity NPC120099
0.6 Remote Similarity NPC472459
0.6 Remote Similarity NPC117260
0.5854 Remote Similarity NPC34531
0.5833 Remote Similarity NPC287889
0.5783 Remote Similarity NPC67037
0.5783 Remote Similarity NPC255615
0.5761 Remote Similarity NPC156869
0.575 Remote Similarity NPC78697
0.5747 Remote Similarity NPC307938
0.5652 Remote Similarity NPC275454
0.5543 Remote Similarity NPC187379
0.5543 Remote Similarity NPC29958
0.5529 Remote Similarity NPC135599
0.5529 Remote Similarity NPC73855
0.5529 Remote Similarity NPC113968
0.5529 Remote Similarity NPC328940
0.5529 Remote Similarity NPC277174
0.5529 Remote Similarity NPC606877
0.5517 Remote Similarity NPC58716
0.5484 Remote Similarity NPC471748
0.5476 Remote Similarity NPC288084
0.5465 Remote Similarity NPC127546
0.5465 Remote Similarity NPC57625
0.5465 Remote Similarity NPC173637
0.5465 Remote Similarity NPC317489
0.5465 Remote Similarity NPC238376
0.5465 Remote Similarity NPC223424
0.5465 Remote Similarity NPC600591
0.5392 Remote Similarity NPC219043
0.5333 Remote Similarity NPC28274
0.5326 Remote Similarity NPC4390
0.5326 Remote Similarity NPC254855
0.5326 Remote Similarity NPC94610
0.5287 Remote Similarity NPC112755
0.5287 Remote Similarity NPC170675
0.5287 Remote Similarity NPC261866
0.5281 Remote Similarity NPC222936
0.5275 Remote Similarity NPC223747
0.5227 Remote Similarity NPC146792
0.5227 Remote Similarity NPC156457
0.5227 Remote Similarity NPC189142
0.5227 Remote Similarity NPC77660
0.5222 Remote Similarity NPC175107
0.5222 Remote Similarity NPC481043
0.5213 Remote Similarity NPC139320
0.5213 Remote Similarity NPC609888
0.5205 Remote Similarity NPC179271
0.5172 Remote Similarity NPC111929
0.5172 Remote Similarity NPC320283
0.5172 Remote Similarity NPC41121
0.5165 Remote Similarity NPC601144
0.5161 Remote Similarity NPC116864
0.5161 Remote Similarity NPC244776
0.5128 Remote Similarity NPC609179
0.5114 Remote Similarity NPC45618
0.5114 Remote Similarity NPC108831
0.5114 Remote Similarity NPC182634
0.5111 Remote Similarity NPC42773
0.5111 Remote Similarity NPC45522
0.5111 Remote Similarity NPC138540
0.5111 Remote Similarity NPC599850
0.51 Remote Similarity NPC76831
0.5096 Remote Similarity NPC292019
0.5096 Remote Similarity NPC48984
0.5096 Remote Similarity NPC202908
0.5068 Remote Similarity NPC169749
0.5068 Remote Similarity NPC20791
0.5063 Remote Similarity NPC125062
0.5056 Remote Similarity NPC265530
0.5056 Remote Similarity NPC136042
0.5055 Remote Similarity NPC219904
0.5054 Remote Similarity NPC170052
0.5054 Remote Similarity NPC135846
0.5045 Remote Similarity NPC192539

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC545857 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
0.5068 Remote Similarity NPD1512 Phase 3

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