Natural Product: NPC93974

Natural Product IDNPC93974
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 JJOUBYOHNYJCOU-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 10291003
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0000337] Flavans
          • [CHEMONTID:0003642] 8-prenylated flavans
            • [CHEMONTID:0003508] 8-prenylated flavanones

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 JJOUBYOHNYJCOU-UHFFFAOYSA-N
Standard InCHI InChI=1S/C20H20O5/c1-11(2)3-5-14-16(22)8-7-15-18(24)10-19(25-20(14)15)13-6-4-12(21)9-17(13)23/h3-4,6-9,19,21-23H,5,10H2,1-2H3
SMILES CC(=CCc1c(ccc2C(=O)CC(c3ccc(cc3O)O)Oc12)O)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   340.13 Volume:   351.666
?
Van der Waals volume.
Dense:   0.967 LogP:   3.366
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.167
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.428
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   19.0
TPSA:   86.99
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   3.0 Rings:   3.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.735 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.254 Fsp3:   0.25
MCE-18:   60.04
?
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:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.789 Fluc inhibitor:   0.613
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.599
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.514
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.402 Promiscuous compounds:   0.016

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.034 MDCK Permeability:   -4.792
Pgp-inhibitor:   0.684 Pgp-substrate:   0.024
PAMPA:   0.101
?
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):   0.04
20% Bioavailability (F20%):   0.951 30% Bioavailability (F30%):   0.998
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.001 MRP1:   0.87
Plasma Protein Binding (PPB):   92.459% Volume Distribution (VD):   0.551
Fu: 8.885%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.972
OATP1B3 inhibitor:   0.992 BCRP inhibitor:   0.993
BSEP inhibitor:   0.658

ADMET: Metabolism

CYP1A2-inhibitor:   0.03 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.967 CYP2C19-substrate:   1.0
CYP2C9-inhibitor:   0.271 CYP2C9-substrate:   0.682
CYP2D6-inhibitor:   0.858 CYP2D6-substrate:   0.778
CYP3A4-inhibitor:   0.012 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.001 CYP2C8-inhibitor:   1.0
HLM stability:   1.0
?
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):  2.953 Half-life (T1/2):  1.853

ADMET: Toxicity

hERG Blockers:  0.093 hERG Blockers (10um):  0.597
Human Hepatotoxicity (H-HT):  0.682 Drug-induced Liver Injury (DILI):  0.361
AMES Toxicity:  0.697 Rat Oral Acute Toxicity:  0.774
Maximum Recommended Daily Dose:  0.655 Skin Sensitization:  0.897
Carcinogencity:  0.555 Eye Corrosion:  0.001
Eye Irritation:  0.923 Respiratory Toxicity:  0.867
Drug-induced Neurotoxicity:  0.454 Ototoxicity:  0.47
Hematotoxicity:  0.116 Drug-induced Nephrotoxicity:  0.64
Genotoxicity:  0.965 RPMI-8226 Immunitoxicity:  0.088
A549 Cytotoxicity:  0.513 Hek293 Cytotoxicity:  0.853
BCF:   1.534
?
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:   4.547
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.662
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.232
?
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
NPO11144 Centella asiatica Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[ 17560738]
NPO11144 Centella asiatica Species Apiaceae Eukaryota n.a. n.a. n.a. DOI[10.1007/s11816-015-0350-y]
NPO11144 Centella asiatica Species Apiaceae Eukaryota n.a. aerial part n.a. PMID[17520525]
NPO28809 Cullen corylifolium Species Fabaceae Eukaryota n.a. fruit n.a. PMID[20663508]
NPO11144 Centella asiatica Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[22966846]
NPO28809 Cullen corylifolium Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[24507928]
NPO28809 Cullen corylifolium Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[9544566]
NPO28809 Cullen corylifolium Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11144 Centella asiatica Species Apiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11144 Centella asiatica Species Apiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO11144 Centella asiatica Species Apiaceae Eukaryota n.a. n.a. n.a. Database[MetaboLights]
NPO28809 Cullen corylifolium Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO11144 Centella asiatica Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO11144 Centella asiatica Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO11144 Centella asiatica Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO28809 Cullen corylifolium Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO28809 Cullen corylifolium Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11144 Centella asiatica Species Apiaceae 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 NPC93974 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 NPC91560
0.8 Intermediate Similarity NPC164980
0.7544 Intermediate Similarity NPC324436
0.7544 Intermediate Similarity NPC78
0.7258 Intermediate Similarity NPC473015
0.7241 Intermediate Similarity NPC236766
0.7241 Intermediate Similarity NPC150408
0.7119 Intermediate Similarity NPC149026
0.6885 Remote Similarity NPC285555
0.6724 Remote Similarity NPC103420
0.6719 Remote Similarity NPC36275
0.6418 Remote Similarity NPC477957
0.6324 Remote Similarity NPC479215
0.6324 Remote Similarity NPC477958
0.629 Remote Similarity NPC75049
0.6269 Remote Similarity NPC479211
0.619 Remote Similarity NPC197252
0.6176 Remote Similarity NPC479213
0.6143 Remote Similarity NPC609256
0.6129 Remote Similarity NPC107572
0.6129 Remote Similarity NPC306829
0.6129 Remote Similarity NPC32739
0.6094 Remote Similarity NPC223500
0.6087 Remote Similarity NPC214774
0.6056 Remote Similarity NPC132592
0.6029 Remote Similarity NPC328164
0.6 Remote Similarity NPC479212
0.5965 Remote Similarity NPC472460
0.5915 Remote Similarity NPC101793
0.5775 Remote Similarity NPC195621
0.5758 Remote Similarity NPC182852
0.5692 Remote Similarity NPC66515
0.5672 Remote Similarity NPC485620
0.5672 Remote Similarity NPC473996
0.5652 Remote Similarity NPC300988
0.5606 Remote Similarity NPC76338
0.5606 Remote Similarity NPC250242
0.5571 Remote Similarity NPC479214
0.5538 Remote Similarity NPC221432
0.5538 Remote Similarity NPC257097
0.5522 Remote Similarity NPC485610
0.5507 Remote Similarity NPC278249
0.5507 Remote Similarity NPC223812
0.5484 Remote Similarity NPC246648
0.5469 Remote Similarity NPC76372
0.5469 Remote Similarity NPC37496
0.5455 Remote Similarity NPC310130
0.5441 Remote Similarity NPC10990
0.5342 Remote Similarity NPC473013
0.5303 Remote Similarity NPC265040
0.5303 Remote Similarity NPC102540
0.5303 Remote Similarity NPC148757
0.5278 Remote Similarity NPC473016
0.5278 Remote Similarity NPC485617
0.5256 Remote Similarity NPC301256
0.5231 Remote Similarity NPC143896
0.5224 Remote Similarity NPC68104
0.5224 Remote Similarity NPC243171
0.5224 Remote Similarity NPC482705
0.5217 Remote Similarity NPC161506
0.5211 Remote Similarity NPC166934
0.5205 Remote Similarity NPC77794
0.5205 Remote Similarity NPC225660
0.5167 Remote Similarity NPC295261
0.5167 Remote Similarity NPC296490
0.5152 Remote Similarity NPC39329
0.5152 Remote Similarity NPC285040
0.5152 Remote Similarity NPC51032
0.5135 Remote Similarity NPC479217
0.5072 Remote Similarity NPC291878
0.5072 Remote Similarity NPC608140

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC93974 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