Natural Product: NPC214496

Natural Product IDNPC214496
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 RTRPDMVGOFRVOY-LNBCOLIQSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 101288288
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0001111] Flavonoid glycosides
          • [CHEMONTID:0001583] Flavonoid O-glycosides
            • [CHEMONTID:0003540] Flavonoid-8-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 RTRPDMVGOFRVOY-LNBCOLIQSA-N
Standard InCHI InChI=1S/C22H22O12/c1-31-14-4-8(2-3-9(14)24)13-6-11(26)16-10(25)5-12(27)20(21(16)32-13)34-22-19(30)18(29)17(28)15(7-23)33-22/h2-6,15,17-19,22-25,27-30H,7H2,1H3/t15-,17-,18+,19-,22+/m1/s1
SMILES COc1cc(ccc1O)c1cc(=O)c2c(cc(c(c2o1)O[C@H]1[C@@H]([C@H]([C@@H]([C@@H](CO)O1)O)O)O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   478.11 Volume:   439.233
?
Van der Waals volume.
Dense:   1.089 LogP:   0.959
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.352
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.382
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   24.0
TPSA:   199.51
?
Topological Polar Surface Area.
 H-Bond Acceptor:   12.0
H-Bond Donor:   7.0 Rings:   4.0
Heavy Atoms:   12.0

MedChem Properties

QED Drug-Likeness Score:   0.254 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.016 Fsp3:   0.318
MCE-18:   90.31
?
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:   0
Colloidal aggregators:   0.642 Fluc inhibitor:   0.283
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.96
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.897
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.112 Promiscuous compounds:   0.736

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.233 MDCK Permeability:   -5.318
Pgp-inhibitor:   0.0 Pgp-substrate:   0.348
PAMPA:   0.918
?
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):   0.248
20% Bioavailability (F20%):   0.299 30% Bioavailability (F30%):   0.982
50% Bioavailability (F50%):   0.998

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.003 MRP1:   0.321
Plasma Protein Binding (PPB):   86.273% Volume Distribution (VD):   -0.064
Fu: 11.734%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.9
BSEP inhibitor:   0.006

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.04 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.021 CYP2D6-substrate:   0.234
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.054
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.179
HLM stability:   0.202
?
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):  2.805 Half-life (T1/2):  3.793

ADMET: Toxicity

hERG Blockers:  0.013 hERG Blockers (10um):  0.116
Human Hepatotoxicity (H-HT):  0.576 Drug-induced Liver Injury (DILI):  0.918
AMES Toxicity:  0.873 Rat Oral Acute Toxicity:  0.05
Maximum Recommended Daily Dose:  0.11 Skin Sensitization:  0.993
Carcinogencity:  0.271 Eye Corrosion:  0.0
Eye Irritation:  0.62 Respiratory Toxicity:  0.072
Drug-induced Neurotoxicity:  0.003 Ototoxicity:  0.771
Hematotoxicity:  0.174 Drug-induced Nephrotoxicity:  0.326
Genotoxicity:  0.892 RPMI-8226 Immunitoxicity:  0.119
A549 Cytotoxicity:  0.372 Hek293 Cytotoxicity:  0.457
BCF:   0.472
?
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:   3.045
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.296
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.553
?
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]
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[COCONUT]
NPO15721 Derris reticulata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16297 Gentiana arisanensis Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16918 Ballota lanata Species Lamiaceae 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]
NPO16297 Gentiana arisanensis Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15721 Derris reticulata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16918 Ballota lanata Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18413 Eucalyptus ovata Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12948 Solanum dulcamara Species Solanaceae 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 NPC214496 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
0.7375 Intermediate Similarity NPC311830
0.725 Intermediate Similarity NPC601710
0.716 Intermediate Similarity NPC602805
0.6829 Remote Similarity NPC601144
0.679 Remote Similarity NPC198324
0.6543 Remote Similarity NPC282987
0.6543 Remote Similarity NPC8573
0.6543 Remote Similarity NPC259152
0.6471 Remote Similarity NPC203050
0.6471 Remote Similarity NPC225434
0.6463 Remote Similarity NPC472385
0.6163 Remote Similarity NPC88023
0.6163 Remote Similarity NPC309025
0.6154 Remote Similarity NPC94777
0.6047 Remote Similarity NPC101026
0.6047 Remote Similarity NPC488077
0.6047 Remote Similarity NPC197285
0.6023 Remote Similarity NPC4390
0.5955 Remote Similarity NPC472607
0.5952 Remote Similarity NPC93337
0.593 Remote Similarity NPC191306
0.5909 Remote Similarity NPC488072
0.5909 Remote Similarity NPC601586
0.5882 Remote Similarity NPC105025
0.5882 Remote Similarity NPC45638
0.5862 Remote Similarity NPC22832
0.5862 Remote Similarity NPC243930
0.5833 Remote Similarity NPC39360
0.5833 Remote Similarity NPC29763
0.5833 Remote Similarity NPC210003
0.5833 Remote Similarity NPC143851
0.5814 Remote Similarity NPC201292
0.5795 Remote Similarity NPC206123
0.5795 Remote Similarity NPC607707
0.5765 Remote Similarity NPC95090
0.5765 Remote Similarity NPC146792
0.5765 Remote Similarity NPC27408
0.5765 Remote Similarity NPC189142
0.5765 Remote Similarity NPC77660
0.5747 Remote Similarity NPC609451
0.573 Remote Similarity NPC469931
0.5698 Remote Similarity NPC58716
0.5682 Remote Similarity NPC605067
0.5682 Remote Similarity NPC606560
0.5647 Remote Similarity NPC58053
0.5568 Remote Similarity NPC135277
0.5568 Remote Similarity NPC168584
0.5568 Remote Similarity NPC210094
0.5567 Remote Similarity NPC195257
0.5529 Remote Similarity NPC471416
0.5526 Remote Similarity NPC4455
0.5517 Remote Similarity NPC186807
0.5517 Remote Similarity NPC610763
0.5465 Remote Similarity NPC261866
0.5465 Remote Similarity NPC45618
0.5455 Remote Similarity NPC222936
0.5455 Remote Similarity NPC325555
0.5455 Remote Similarity NPC226304
0.5444 Remote Similarity NPC223747
0.5444 Remote Similarity NPC111249
0.5405 Remote Similarity NPC301323
0.5333 Remote Similarity NPC148710
0.5333 Remote Similarity NPC120099
0.5333 Remote Similarity NPC188203
0.5333 Remote Similarity NPC609478
0.5287 Remote Similarity NPC77672
0.5287 Remote Similarity NPC133671
0.5287 Remote Similarity NPC135391
0.5287 Remote Similarity NPC83283
0.5287 Remote Similarity NPC78263
0.5287 Remote Similarity NPC250069
0.5281 Remote Similarity NPC101191
0.5256 Remote Similarity NPC183950
0.5227 Remote Similarity NPC145038
0.5227 Remote Similarity NPC56077
0.5227 Remote Similarity NPC281131
0.5227 Remote Similarity NPC168822
0.5227 Remote Similarity NPC253662
0.5227 Remote Similarity NPC179950
0.5227 Remote Similarity NPC88789
0.5227 Remote Similarity NPC491374
0.5169 Remote Similarity NPC84362
0.5169 Remote Similarity NPC488080
0.5169 Remote Similarity NPC169977
0.5165 Remote Similarity NPC284960
0.5128 Remote Similarity NPC128863
0.5111 Remote Similarity NPC42773
0.5111 Remote Similarity NPC472459
0.5111 Remote Similarity NPC182045
0.5111 Remote Similarity NPC475942
0.5111 Remote Similarity NPC21100
0.5111 Remote Similarity NPC45522
0.5067 Remote Similarity NPC131624
0.5063 Remote Similarity NPC227325
0.5055 Remote Similarity NPC60735
0.5055 Remote Similarity NPC26230
0.5054 Remote Similarity NPC48773

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC214496 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