Natural Product: NPC133300

Natural Product IDNPC133300
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 WJJFWGUVMIUWGG-QOUKUZOOSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 5459939
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0001111] Flavonoid glycosides
          • [CHEMONTID:0001583] Flavonoid O-glycosides

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 WJJFWGUVMIUWGG-QOUKUZOOSA-N
Standard InCHI InChI=1S/C21H20O12/c22-6-14-16(27)18(29)19(30)21(32-14)33-20-11(26)5-13-15(17(20)28)10(25)4-12(31-13)7-1-2-8(23)9(24)3-7/h1-5,14,16,18-19,21-24,26-30H,6H2/t14-,16-,18+,19-,21+/m1/s1
SMILES c1cc(c(cc1c1cc(=O)c2c(cc(c(c2O)O[C@H]2[C@@H]([C@H]([C@@H]([C@@H](CO)O2)O)O)O)O)o1)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   464.1 Volume:   421.937
?
Van der Waals volume.
Dense:   1.1 LogP:   0.669
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.08
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.496
?
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:   4.066 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:   0.708 Fluc inhibitor:   0.3
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.976
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.808
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.31 Promiscuous compounds:   0.888

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.287 MDCK Permeability:   -5.072
Pgp-inhibitor:   0.0 Pgp-substrate:   0.077
PAMPA:   0.972
?
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):   0.125
20% Bioavailability (F20%):   0.904 30% Bioavailability (F30%):   0.999
50% Bioavailability (F50%):   0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.004 MRP1:   0.355
Plasma Protein Binding (PPB):   83.181% Volume Distribution (VD):   -0.046
Fu: 14.509%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.998
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.599
BSEP inhibitor:   0.0

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:   0.004 CYP2D6-substrate:   0.713
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.002
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.903
HLM stability:   0.141
?
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):  3.598 Half-life (T1/2):  3.607

ADMET: Toxicity

hERG Blockers:  0.017 hERG Blockers (10um):  0.156
Human Hepatotoxicity (H-HT):  0.501 Drug-induced Liver Injury (DILI):  0.942
AMES Toxicity:  0.831 Rat Oral Acute Toxicity:  0.042
Maximum Recommended Daily Dose:  0.113 Skin Sensitization:  0.999
Carcinogencity:  0.239 Eye Corrosion:  0.0
Eye Irritation:  0.741 Respiratory Toxicity:  0.015
Drug-induced Neurotoxicity:  0.0 Ototoxicity:  0.883
Hematotoxicity:  0.097 Drug-induced Nephrotoxicity:  0.09
Genotoxicity:  0.953 RPMI-8226 Immunitoxicity:  0.031
A549 Cytotoxicity:  0.577 Hek293 Cytotoxicity:  0.327
BCF:   0.46
?
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:   4.353
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.647
?
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
NPO16297 Gentiana arisanensis Species Gentianaceae Eukaryota Whole Plant Yu Shieh, Chiayi Hsieh, Taiwan 1994-APR PMID[9287421]
NPO16918 Ballota lanata Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16297 Gentiana arisanensis Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20125 Cleistanthus schlechteri Species Phyllanthaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15721 Derris reticulata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO22965 Saussurea elegans Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12948 Solanum dulcamara Species Solanaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18413 Eucalyptus ovata Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12948 Solanum dulcamara Species Solanaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO12948 Solanum dulcamara Species Solanaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO12948 Solanum dulcamara Species Solanaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO22965 Saussurea elegans Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23191 Plectranthus striatus Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12948 Solanum dulcamara Species Solanaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18413 Eucalyptus ovata Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16918 Ballota lanata Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22024 Agathosma serpyllacea Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15721 Derris reticulata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16297 Gentiana arisanensis Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20125 Cleistanthus schlechteri Species Phyllanthaceae 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 NPC133300 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
0.7703 Intermediate Similarity NPC45638
0.76 Intermediate Similarity NPC201292
0.7333 Intermediate Similarity NPC189142
0.7333 Intermediate Similarity NPC77660
0.7237 Intermediate Similarity NPC58716
0.7143 Intermediate Similarity NPC42773
0.7143 Intermediate Similarity NPC45522
0.6883 Remote Similarity NPC168822
0.6667 Remote Similarity NPC93337
0.6625 Remote Similarity NPC191306
0.6582 Remote Similarity NPC105025
0.6543 Remote Similarity NPC601710
0.6543 Remote Similarity NPC605067
0.6463 Remote Similarity NPC602805
0.6456 Remote Similarity NPC259152
0.6395 Remote Similarity NPC607513
0.6375 Remote Similarity NPC488080
0.6375 Remote Similarity NPC169977
0.6329 Remote Similarity NPC58053
0.6329 Remote Similarity NPC39360
0.6329 Remote Similarity NPC29763
0.6329 Remote Similarity NPC210003
0.6329 Remote Similarity NPC143851
0.6324 Remote Similarity NPC100887
0.625 Remote Similarity NPC145038
0.625 Remote Similarity NPC56077
0.625 Remote Similarity NPC281131
0.625 Remote Similarity NPC488073
0.625 Remote Similarity NPC253662
0.625 Remote Similarity NPC146792
0.625 Remote Similarity NPC179950
0.625 Remote Similarity NPC88789
0.625 Remote Similarity NPC491374
0.6222 Remote Similarity NPC472991
0.6173 Remote Similarity NPC186807
0.6145 Remote Similarity NPC101026
0.6145 Remote Similarity NPC22832
0.6145 Remote Similarity NPC488077
0.6145 Remote Similarity NPC601144
0.6125 Remote Similarity NPC19709
0.6125 Remote Similarity NPC83283
0.6111 Remote Similarity NPC150767
0.6098 Remote Similarity NPC117260
0.6071 Remote Similarity NPC311830
0.6049 Remote Similarity NPC282987
0.6049 Remote Similarity NPC277205
0.6049 Remote Similarity NPC37919
0.6047 Remote Similarity NPC8856
0.6024 Remote Similarity NPC609451
0.6023 Remote Similarity NPC3583
0.5976 Remote Similarity NPC245014
0.5976 Remote Similarity NPC305811
0.5976 Remote Similarity NPC610763
0.5926 Remote Similarity NPC261866
0.5926 Remote Similarity NPC45618
0.5882 Remote Similarity NPC88023
0.5882 Remote Similarity NPC309025
0.5862 Remote Similarity NPC254540
0.5854 Remote Similarity NPC95090
0.5854 Remote Similarity NPC27408
0.5854 Remote Similarity NPC136042
0.5854 Remote Similarity NPC609879
0.5833 Remote Similarity NPC488071
0.5783 Remote Similarity NPC84362
0.575 Remote Similarity NPC34287
0.5732 Remote Similarity NPC77672
0.5732 Remote Similarity NPC133671
0.5732 Remote Similarity NPC135391
0.5732 Remote Similarity NPC78263
0.5732 Remote Similarity NPC250069
0.5714 Remote Similarity NPC599850
0.5696 Remote Similarity NPC183036
0.5667 Remote Similarity NPC218488
0.5638 Remote Similarity NPC256760
0.5632 Remote Similarity NPC190003
0.5618 Remote Similarity NPC603300
0.5604 Remote Similarity NPC115674
0.5581 Remote Similarity NPC243930
0.5543 Remote Similarity NPC472992
0.5542 Remote Similarity NPC19388
0.5542 Remote Similarity NPC240431
0.5542 Remote Similarity NPC55786
0.5529 Remote Similarity NPC475942
0.5517 Remote Similarity NPC605784
0.5517 Remote Similarity NPC607707
0.5506 Remote Similarity NPC472607
0.5495 Remote Similarity NPC210073
0.5495 Remote Similarity NPC156869
0.5488 Remote Similarity NPC67037
0.5488 Remote Similarity NPC255615
0.5484 Remote Similarity NPC65711
0.5455 Remote Similarity NPC203050
0.5455 Remote Similarity NPC225434
0.5422 Remote Similarity NPC53545
0.5402 Remote Similarity NPC284960
0.5402 Remote Similarity NPC197285
0.5385 Remote Similarity NPC78734
0.5376 Remote Similarity NPC126784
0.5376 Remote Similarity NPC241423
0.5376 Remote Similarity NPC488074
0.5349 Remote Similarity NPC222936
0.5349 Remote Similarity NPC21100
0.5333 Remote Similarity NPC606546
0.5294 Remote Similarity NPC297987
0.5294 Remote Similarity NPC64305
0.5294 Remote Similarity NPC323593
0.5294 Remote Similarity NPC203500
0.5287 Remote Similarity NPC60735
0.5287 Remote Similarity NPC26230
0.5278 Remote Similarity NPC241498
0.5275 Remote Similarity NPC29958
0.5238 Remote Similarity NPC473043
0.5238 Remote Similarity NPC331652
0.5233 Remote Similarity NPC84265
0.5233 Remote Similarity NPC24043
0.5227 Remote Similarity NPC120099
0.5227 Remote Similarity NPC606560
0.5227 Remote Similarity NPC609478
0.5222 Remote Similarity NPC4390
0.5217 Remote Similarity NPC471748
0.5176 Remote Similarity NPC127546
0.5176 Remote Similarity NPC110349
0.5176 Remote Similarity NPC57625
0.5176 Remote Similarity NPC173637
0.5176 Remote Similarity NPC317489
0.5176 Remote Similarity NPC223424
0.5176 Remote Similarity NPC600591
0.5172 Remote Similarity NPC472459
0.5135 Remote Similarity NPC25270
0.5135 Remote Similarity NPC256283
0.5116 Remote Similarity NPC8573
0.5114 Remote Similarity NPC285197
0.5111 Remote Similarity NPC488072
0.5111 Remote Similarity NPC601586
0.5109 Remote Similarity NPC480466
0.5104 Remote Similarity NPC229409
0.5102 Remote Similarity NPC470445
0.5096 Remote Similarity NPC132111
0.5067 Remote Similarity NPC83508
0.5056 Remote Similarity NPC21666
0.5056 Remote Similarity NPC486578
0.5055 Remote Similarity NPC254855
0.5055 Remote Similarity NPC94610
0.5055 Remote Similarity NPC172807
0.5051 Remote Similarity NPC470446
0.5051 Remote Similarity NPC253685

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC133300 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
NPD

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