Natural Product: NPC131296

Natural Product IDNPC131296
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 AWMHMGFGCLBSAY-GOSISDBHSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 28125521
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000145] Coumarins and derivatives
        • [CHEMONTID:0000358] Furanocoumarins
          • [CHEMONTID:0002569] Linear furanocoumarins
            • [CHEMONTID:0000202] Psoralens

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 AWMHMGFGCLBSAY-GOSISDBHSA-N
Standard InCHI InChI=1S/C21H24O5/c1-7-20(3,4)15-9-13-8-14-10-18(21(5,6)26-12(2)22)24-16(14)11-17(13)25-19(15)23/h7-9,11,18H,1,10H2,2-6H3/t18-/m1/s1
SMILES C=CC(C)(C)c1cc2cc3C[C@H](C(C)(C)OC(=O)C)Oc3cc2oc1=O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   356.16 Volume:   371.599
?
Van der Waals volume.
Dense:   0.958 LogP:   4.029
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.345
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.026
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   18.0
TPSA:   65.74
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   0.0 Rings:   3.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.472 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.7 Fsp3:   0.429
MCE-18:   72.067
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Accepted GSK Rule:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.464 Fluc inhibitor:   0.352
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.951
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.476
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.35 Promiscuous compounds:   0.175

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.965 MDCK Permeability:   -4.785
Pgp-inhibitor:   0.506 Pgp-substrate:   0.0
PAMPA:   0.099
?
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):   0.0
20% Bioavailability (F20%):   0.893 30% Bioavailability (F30%):   0.911
50% Bioavailability (F50%):   0.993

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   1.0
Plasma Protein Binding (PPB):   92.291% Volume Distribution (VD):   0.26
Fu: 6.811%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.151
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.027 CYP1A2-substrate:   0.987
CYP2C19-inhibitor:   0.967 CYP2C19-substrate:   0.958
CYP2C9-inhibitor:   0.72 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.012 CYP2D6-substrate:   0.94
CYP3A4-inhibitor:   0.991 CYP3A4-substrate:   0.999
CYP2B6-substrate:   0.313 CYP2C8-inhibitor:   1.0
HLM stability:   0.994
?
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):  5.967 Half-life (T1/2):  0.931

ADMET: Toxicity

hERG Blockers:  0.058 hERG Blockers (10um):  0.293
Human Hepatotoxicity (H-HT):  0.445 Drug-induced Liver Injury (DILI):  0.84
AMES Toxicity:  0.523 Rat Oral Acute Toxicity:  0.647
Maximum Recommended Daily Dose:  0.671 Skin Sensitization:  0.788
Carcinogencity:  0.841 Eye Corrosion:  0.306
Eye Irritation:  0.962 Respiratory Toxicity:  0.548
Drug-induced Neurotoxicity:  0.441 Ototoxicity:  0.195
Hematotoxicity:  0.251 Drug-induced Nephrotoxicity:  0.227
Genotoxicity:  0.9 RPMI-8226 Immunitoxicity:  0.056
A549 Cytotoxicity:  0.06 Hek293 Cytotoxicity:  0.237
BCF:   1.271
?
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:   3.902
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.454
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.073
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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
NPO3854 Ruta graveolens Species Rutaceae Eukaryota n.a. n.a. n.a. DOI[10.1042/BA20070200]
NPO3854 Ruta graveolens Species Rutaceae Eukaryota leaves n.a. n.a. PMID[12568545]
NPO3854 Ruta graveolens Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[19191562]
NPO3854 Ruta graveolens Species Rutaceae Eukaryota Whole Plants n.a. n.a. PMID[28093914]
NPO3854 Ruta graveolens Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3854 Ruta graveolens Species Rutaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO3854 Ruta graveolens Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO3854 Ruta graveolens Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]

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
NPT26641 Cell line P3HR-1 Homo sapiens CC50 > 140000.0 nM PMID[28093914]
NPT164 Organism Human herpesvirus 4 Human herpesvirus 4 IC50 = 13800.0 nM PMID[28093914]
NPT2 Others Unspecified n.a. Ratio CC50/IC50 > 10.0 n.a. PMID[28093914]

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 NPC131296 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 NPC326489
1.0 High Similarity NPC283331
0.8548 High Similarity NPC488325
0.8154 Intermediate Similarity NPC488332
0.803 Intermediate Similarity NPC488333
0.7465 Intermediate Similarity NPC488334
0.7361 Intermediate Similarity NPC488326
0.7353 Intermediate Similarity NPC488324
0.6883 Remote Similarity NPC488327
0.6774 Remote Similarity NPC235682
0.6774 Remote Similarity NPC608821
0.6667 Remote Similarity NPC488329
0.6329 Remote Similarity NPC488330
0.6329 Remote Similarity NPC488343
0.625 Remote Similarity NPC488328
0.6203 Remote Similarity NPC488342
0.619 Remote Similarity NPC611256
0.6 Remote Similarity NPC7526
0.6 Remote Similarity NPC222036
0.6 Remote Similarity NPC14248
0.5846 Remote Similarity NPC109515
0.5522 Remote Similarity NPC157212

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC131296 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