Natural Product: NPC1517

Natural Product IDNPC1517
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 BCGZYQZPALWTAY-NRFANRHFSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 101326868
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0000337] Flavans
          • [CHEMONTID:0003646] 6-prenylated flavans
            • [CHEMONTID:0003507] 6-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 BCGZYQZPALWTAY-NRFANRHFSA-N
Standard InCHI InChI=1S/C26H28O6/c1-14(2)6-8-17-23(29)22-20(28)13-21(16-9-7-15(30-5)12-19(16)27)31-25(22)18-10-11-26(3,4)32-24(17)18/h6-7,9-12,21,27,29H,8,13H2,1-5H3/t21-/m0/s1
SMILES CC(=CCc1c(c2C(=O)C[C@@H](c3ccc(cc3O)OC)Oc2c2C=CC(C)(C)Oc12)O)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   436.19 Volume:   453.039
?
Van der Waals volume.
Dense:   0.963 LogP:   5.239
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.964
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.456
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   24.0
TPSA:   85.22
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   2.0 Rings:   4.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.615 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.662 Fsp3:   0.346
MCE-18:   85.629
?
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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.975 Fluc inhibitor:   0.697
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.831
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.911
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.254 Promiscuous compounds:   0.236

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.006 MDCK Permeability:   -4.738
Pgp-inhibitor:   0.996 Pgp-substrate:   0.003
PAMPA:   0.055
?
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):   0.052
20% Bioavailability (F20%):   0.962 30% Bioavailability (F30%):   0.998
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.002 MRP1:   0.922
Plasma Protein Binding (PPB):   96.911% Volume Distribution (VD):   0.229
Fu: 2.657%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   0.976 BCRP inhibitor:   0.993
BSEP inhibitor:   0.998

ADMET: Metabolism

CYP1A2-inhibitor:   0.001 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.998 CYP2C19-substrate:   1.0
CYP2C9-inhibitor:   0.028 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.666
CYP3A4-inhibitor:   0.004 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):  5.719 Half-life (T1/2):  1.206

ADMET: Toxicity

hERG Blockers:  0.111 hERG Blockers (10um):  0.482
Human Hepatotoxicity (H-HT):  0.723 Drug-induced Liver Injury (DILI):  0.699
AMES Toxicity:  0.78 Rat Oral Acute Toxicity:  0.841
Maximum Recommended Daily Dose:  0.755 Skin Sensitization:  0.897
Carcinogencity:  0.643 Eye Corrosion:  0.0
Eye Irritation:  0.592 Respiratory Toxicity:  0.962
Drug-induced Neurotoxicity:  0.744 Ototoxicity:  0.622
Hematotoxicity:  0.265 Drug-induced Nephrotoxicity:  0.857
Genotoxicity:  0.843 RPMI-8226 Immunitoxicity:  0.21
A549 Cytotoxicity:  0.699 Hek293 Cytotoxicity:  0.508
BCF:   2.008
?
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:   5.099
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   7.364
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   6.676
?
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
NPO453 Teucrium marum Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[15763383]
NPO12927 Astragalus bicuspis Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[18771242]
NPO10684 Parameria laevigata Species Apocynaceae Eukaryota n.a. bark n.a. PMID[21875098]
NPO14098 Styrax agrestis Species Styracaceae Eukaryota fruits Thua Thien, Hue district, Vietnam n.a. PMID[21939219]
NPO14098 Styrax agrestis Species Styracaceae Eukaryota n.a. ripe fruit n.a. PMID[21939219]
NPO453 Teucrium marum Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[37539184]
NPO7995 Tolypocladium album Species Ophiocordycipitaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11386 Chelonaplysilla violacea Species Darwinellidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO453 Teucrium marum Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO6748 Strongylodesma algoaensis n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO14686 Justicia adhatoda Species Acanthaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8612 Flemingia macrophylla Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14098 Styrax agrestis Species Styracaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7255 Pterocarpus indicus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7255 Pterocarpus indicus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO453 Teucrium marum Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO10684 Parameria laevigata Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO10684 Parameria laevigata Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO453 Teucrium marum Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO14686 Justicia adhatoda Species Acanthaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO7255 Pterocarpus indicus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO25132 [clostridium] cellulolyticum Species Ruminococcaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO7255 Pterocarpus indicus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO453 Teucrium marum Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10684 Parameria laevigata Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6748 Strongylodesma algoaensis n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO11574 Usnea canariensis Species Parmeliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12927 Astragalus bicuspis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10059 Hyoscyamus pusillus Species Solanaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14686 Justicia adhatoda Species Acanthaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14098 Styrax agrestis Species Styracaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17134 Amietophrynus regularis Species Bufonidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8612 Flemingia macrophylla Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11386 Chelonaplysilla violacea Species Darwinellidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7995 Tolypocladium album Species Ophiocordycipitaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8380 Hibiscus schizopetalus Species Malvaceae 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 NPC1517 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
0.7857 Intermediate Similarity NPC83357
0.7826 Intermediate Similarity NPC214774
0.7391 Intermediate Similarity NPC246948
0.7361 Intermediate Similarity NPC192686
0.7361 Intermediate Similarity NPC284820
0.726 Intermediate Similarity NPC119209
0.6282 Remote Similarity NPC283234
0.6234 Remote Similarity NPC54577
0.6184 Remote Similarity NPC67805
0.6104 Remote Similarity NPC195621
0.5972 Remote Similarity NPC311741
0.5584 Remote Similarity NPC142405
0.5513 Remote Similarity NPC180301
0.5375 Remote Similarity NPC267375
0.5333 Remote Similarity NPC285555
0.527 Remote Similarity NPC148757
0.5256 Remote Similarity NPC301276
0.525 Remote Similarity NPC161191
0.5244 Remote Similarity NPC609256
0.52 Remote Similarity NPC176229
0.519 Remote Similarity NPC39752
0.5135 Remote Similarity NPC285040
0.5067 Remote Similarity NPC265040
0.5065 Remote Similarity NPC608140
0.506 Remote Similarity NPC160821

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC1517 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