Natural Product: NPC293138

Natural Product IDNPC293138
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 RSYUFYQTACJFML-AWKYBWMHSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 9943440
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0000337] Flavans
          • [CHEMONTID:0003012] Flavan-3-ols

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 RSYUFYQTACJFML-AWKYBWMHSA-N
Standard InCHI InChI=1S/C15H14O5/c16-9-3-1-8(2-4-9)15-13(19)7-11-12(18)5-10(17)6-14(11)20-15/h1-6,13,15-19H,7H2/t13?,15-/m1/s1
SMILES c1cc(ccc1[C@@H]1C(Cc2c(cc(cc2O1)O)O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   274.08 Volume:   270.459
?
Van der Waals volume.
Dense:   1.013 LogP:   0.922
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.348
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.435
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   17.0
TPSA:   90.15
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   4.0 Rings:   3.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.637 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.185 Fsp3:   0.2
MCE-18:   56.667
?
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:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.492 Fluc inhibitor:   0.569
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.093
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.199
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.463 Promiscuous compounds:   0.361

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.885 MDCK Permeability:   -4.88
Pgp-inhibitor:   0.007 Pgp-substrate:   0.528
PAMPA:   0.259
?
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%):   0.131 30% Bioavailability (F30%):   0.896
50% Bioavailability (F50%):   0.989

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.014 MRP1:   0.807
Plasma Protein Binding (PPB):   92.583% Volume Distribution (VD):   0.384
Fu: 8.519%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.597
OATP1B3 inhibitor:   0.887 BCRP inhibitor:   0.332
BSEP inhibitor:   0.411

ADMET: Metabolism

CYP1A2-inhibitor:   0.008 CYP1A2-substrate:   0.003
CYP2C19-inhibitor:   0.104 CYP2C19-substrate:   0.001
CYP2C9-inhibitor:   0.876 CYP2C9-substrate:   0.003
CYP2D6-inhibitor:   0.995 CYP2D6-substrate:   0.008
CYP3A4-inhibitor:   0.002 CYP3A4-substrate:   0.002
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.215
HLM stability:   0.194
?
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):  10.617 Half-life (T1/2):  1.761

ADMET: Toxicity

hERG Blockers:  0.198 hERG Blockers (10um):  0.699
Human Hepatotoxicity (H-HT):  0.752 Drug-induced Liver Injury (DILI):  0.034
AMES Toxicity:  0.442 Rat Oral Acute Toxicity:  0.506
Maximum Recommended Daily Dose:  0.767 Skin Sensitization:  0.6
Carcinogencity:  0.221 Eye Corrosion:  0.002
Eye Irritation:  0.975 Respiratory Toxicity:  0.316
Drug-induced Neurotoxicity:  0.458 Ototoxicity:  0.595
Hematotoxicity:  0.034 Drug-induced Nephrotoxicity:  0.171
Genotoxicity:  0.862 RPMI-8226 Immunitoxicity:  0.048
A549 Cytotoxicity:  0.313 Hek293 Cytotoxicity:  0.843
BCF:   1.21
?
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:   3.169
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.279
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.831
?
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
NPO24093 Drynaria fortunei Species Polypodiaceae Eukaryota n.a. n.a. n.a. PMID[21377852]
NPO29757 Acacia catechu Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24093 Drynaria fortunei Species Polypodiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13856 Bergenia purpurascens Species Saxifragaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2340 Caulis spatholobi n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO277 Caulis millettiae n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO1334 Senegalia catechu Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29757 Acacia catechu Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO24093 Drynaria fortunei Species Polypodiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO2340 Caulis spatholobi n.a. n.a. n.a. n.a. n.a. n.a. Database[HerDing]
NPO13856 Bergenia purpurascens Species Saxifragaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO13856 Bergenia purpurascens Species Saxifragaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO1334 Senegalia catechu Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO24093 Drynaria fortunei Species Polypodiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO2340 Caulis spatholobi n.a. n.a. n.a. n.a. n.a. n.a. Database[TCMID]
NPO277 Caulis millettiae n.a. n.a. n.a. n.a. n.a. n.a. Database[TCMID]
NPO29193 Nekemias grossedentata Species Vitaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO29757 Acacia catechu Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO24093 Drynaria fortunei Species Polypodiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO24093 Drynaria fortunei Species Polypodiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO1334 Senegalia catechu Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO1334 Senegalia catechu Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29193 Nekemias grossedentata Species Vitaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24093 Drynaria fortunei Species Polypodiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13856 Bergenia purpurascens Species Saxifragaceae 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 NPC293138 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 NPC207179
1.0 High Similarity NPC167571
1.0 High Similarity NPC278552
0.8222 Intermediate Similarity NPC261619
0.8222 Intermediate Similarity NPC61477
0.8222 Intermediate Similarity NPC78770
0.8222 Intermediate Similarity NPC219876
0.8222 Intermediate Similarity NPC126029
0.8222 Intermediate Similarity NPC15658
0.74 Intermediate Similarity NPC16435
0.74 Intermediate Similarity NPC171932
0.7391 Intermediate Similarity NPC268266
0.7391 Intermediate Similarity NPC42760
0.7391 Intermediate Similarity NPC220825
0.7391 Intermediate Similarity NPC268342
0.7083 Intermediate Similarity NPC47398
0.7083 Intermediate Similarity NPC234333
0.7083 Intermediate Similarity NPC260898
0.7 Intermediate Similarity NPC61946
0.6458 Remote Similarity NPC482472
0.6379 Remote Similarity NPC277331
0.6379 Remote Similarity NPC100482
0.6102 Remote Similarity NPC601999
0.6078 Remote Similarity NPC62290
0.6078 Remote Similarity NPC142731
0.6078 Remote Similarity NPC326506
0.6066 Remote Similarity NPC308402
0.6066 Remote Similarity NPC28440
0.6032 Remote Similarity NPC211561
0.5833 Remote Similarity NPC58190
0.5833 Remote Similarity NPC108811
0.5833 Remote Similarity NPC9636
0.5833 Remote Similarity NPC170103
0.5833 Remote Similarity NPC236202
0.5833 Remote Similarity NPC262911
0.5833 Remote Similarity NPC202742
0.58 Remote Similarity NPC601844
0.5738 Remote Similarity NPC246202
0.5738 Remote Similarity NPC224161
0.5738 Remote Similarity NPC46335
0.5738 Remote Similarity NPC294558
0.5738 Remote Similarity NPC18185
0.5738 Remote Similarity NPC263940
0.5738 Remote Similarity NPC279406
0.5738 Remote Similarity NPC486519
0.5714 Remote Similarity NPC155564
0.5625 Remote Similarity NPC70409
0.5625 Remote Similarity NPC204770
0.5625 Remote Similarity NPC600551
0.5625 Remote Similarity NPC601980
0.5625 Remote Similarity NPC602065
0.5625 Remote Similarity NPC611024
0.5574 Remote Similarity NPC607430
0.5538 Remote Similarity NPC601997
0.5538 Remote Similarity NPC609211
0.5538 Remote Similarity NPC610665
0.5455 Remote Similarity NPC186228
0.5373 Remote Similarity NPC134911
0.5323 Remote Similarity NPC82917
0.5312 Remote Similarity NPC313116
0.5312 Remote Similarity NPC603340
0.5303 Remote Similarity NPC226809
0.5246 Remote Similarity NPC96576
0.5192 Remote Similarity NPC1940
0.5179 Remote Similarity NPC36835
0.5179 Remote Similarity NPC246162
0.5179 Remote Similarity NPC9743
0.5179 Remote Similarity NPC260491
0.5179 Remote Similarity NPC61506
0.5179 Remote Similarity NPC240476
0.5152 Remote Similarity NPC470802
0.5147 Remote Similarity NPC46283
0.5147 Remote Similarity NPC469944
0.5147 Remote Similarity NPC278548
0.5143 Remote Similarity NPC306267
0.5091 Remote Similarity NPC103799
0.5085 Remote Similarity NPC150670
0.5085 Remote Similarity NPC482704
0.5082 Remote Similarity NPC156818

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC293138 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
0.8222 Intermediate Similarity NPD1612 Clinical (unspecified phase)
0.8222 Intermediate Similarity NPD1613 Phase 4

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