Natural Product: NPC203398

Natural Product IDNPC203398
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 FIENOOOOPYEDMI-SATZSMTESA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 44257217
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0002506] Isoflavonoids
        • [CHEMONTID:0000507] Isoflavonoid 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 FIENOOOOPYEDMI-SATZSMTESA-N
Standard InCHI InChI=1S/C21H20O9/c22-8-16-18(25)19(26)20(27)21(30-16)29-12-4-1-10(2-5-12)14-9-28-15-7-11(23)3-6-13(15)17(14)24/h1-7,9,16,18-23,25-27H,8H2/t16?,18-,19?,20?,21-/m0/s1
SMILES c1cc(ccc1c1coc2cc(ccc2c1=O)O)O[C@@H]1C(C([C@H](C(CO)O1)O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   416.11 Volume:   395.567
?
Van der Waals volume.
Dense:   1.052 LogP:   -0.279
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   0.912
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.282
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   24.0
TPSA:   149.82
?
Topological Polar Surface Area.
 H-Bond Acceptor:   9.0
H-Bond Donor:   5.0 Rings:   4.0
Heavy Atoms:   9.0

MedChem Properties

QED Drug-Likeness Score:   0.406 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.655 Fsp3:   0.286
MCE-18:   80.889
?
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:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.479 Fluc inhibitor:   0.353
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.924
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.793
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.319 Promiscuous compounds:   0.272

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.267 MDCK Permeability:   -5.201
Pgp-inhibitor:   0.0 Pgp-substrate:   0.748
PAMPA:   0.996
?
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):   0.551
20% Bioavailability (F20%):   0.812 30% Bioavailability (F30%):   0.98
50% Bioavailability (F50%):   0.995

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.002 MRP1:   0.151
Plasma Protein Binding (PPB):   83.0% Volume Distribution (VD):   0.014
Fu: 18.089%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.24
OATP1B3 inhibitor:   0.897 BCRP inhibitor:   0.311
BSEP inhibitor:   0.159

ADMET: Metabolism

CYP1A2-inhibitor:   0.474 CYP1A2-substrate:   0.048
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.045
CYP2C9-inhibitor:   0.992 CYP2C9-substrate:   0.401
CYP2D6-inhibitor:   0.791 CYP2D6-substrate:   0.001
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.0
?
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):  2.496 Half-life (T1/2):  2.361

ADMET: Toxicity

hERG Blockers:  0.169 hERG Blockers (10um):  0.447
Human Hepatotoxicity (H-HT):  0.651 Drug-induced Liver Injury (DILI):  0.902
AMES Toxicity:  0.818 Rat Oral Acute Toxicity:  0.383
Maximum Recommended Daily Dose:  0.527 Skin Sensitization:  0.115
Carcinogencity:  0.5 Eye Corrosion:  0.0
Eye Irritation:  0.347 Respiratory Toxicity:  0.195
Drug-induced Neurotoxicity:  0.237 Ototoxicity:  0.878
Hematotoxicity:  0.084 Drug-induced Nephrotoxicity:  0.33
Genotoxicity:  0.897 RPMI-8226 Immunitoxicity:  0.087
A549 Cytotoxicity:  0.307 Hek293 Cytotoxicity:  0.658
BCF:   0.651
?
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:   3.355
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.952
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.13
?
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
NPO8707.1 Pueraria montana var. lobata Varieties Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8707.1 Pueraria montana var. lobata Varieties Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO8707.1 Pueraria montana var. lobata Varieties Fabaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO8707.1 Pueraria montana var. lobata Varieties Fabaceae 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 NPC203398 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 NPC258035
0.7568 Intermediate Similarity NPC161749
0.7568 Intermediate Similarity NPC156457
0.7297 Intermediate Similarity NPC45165
0.6842 Remote Similarity NPC135345
0.6795 Remote Similarity NPC73511
0.675 Remote Similarity NPC229729
0.6667 Remote Similarity NPC105511
0.6667 Remote Similarity NPC603782
0.6471 Remote Similarity NPC209560
0.6471 Remote Similarity NPC490700
0.6456 Remote Similarity NPC197896
0.6456 Remote Similarity NPC313163
0.6447 Remote Similarity NPC25547
0.6341 Remote Similarity NPC601607
0.6329 Remote Similarity NPC211014
0.6296 Remote Similarity NPC100720
0.6296 Remote Similarity NPC205076
0.6296 Remote Similarity NPC138540
0.622 Remote Similarity NPC479401
0.5976 Remote Similarity NPC100818
0.5882 Remote Similarity NPC307518
0.5854 Remote Similarity NPC234739
0.5833 Remote Similarity NPC481043
0.5802 Remote Similarity NPC160515
0.5732 Remote Similarity NPC143851
0.5647 Remote Similarity NPC479402
0.5647 Remote Similarity NPC80140
0.5632 Remote Similarity NPC48773
0.5632 Remote Similarity NPC479407
0.5616 Remote Similarity NPC12377
0.5542 Remote Similarity NPC259070
0.5541 Remote Similarity NPC80710
0.5517 Remote Similarity NPC479406
0.5517 Remote Similarity NPC607201
0.5495 Remote Similarity NPC479405
0.5476 Remote Similarity NPC64305
0.5465 Remote Similarity NPC224462
0.5441 Remote Similarity NPC234560
0.5435 Remote Similarity NPC479404
0.5395 Remote Similarity NPC35544
0.5357 Remote Similarity NPC348541
0.5342 Remote Similarity NPC609386
0.5341 Remote Similarity NPC206123
0.5333 Remote Similarity NPC12175
0.5333 Remote Similarity NPC487212
0.5301 Remote Similarity NPC223701
0.5301 Remote Similarity NPC487214
0.5301 Remote Similarity NPC472583
0.5301 Remote Similarity NPC7989
0.5263 Remote Similarity NPC55162
0.5181 Remote Similarity NPC285623
0.5176 Remote Similarity NPC58053
0.5176 Remote Similarity NPC83283
0.5172 Remote Similarity NPC472459
0.5135 Remote Similarity NPC203747
0.5132 Remote Similarity NPC139364
0.5132 Remote Similarity NPC191741
0.5116 Remote Similarity NPC168822
0.5104 Remote Similarity NPC51326
0.507 Remote Similarity NPC242893
0.5065 Remote Similarity NPC200060
0.5062 Remote Similarity NPC78697
0.5057 Remote Similarity NPC186807

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC203398 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
0.7568 Intermediate Similarity NPD4381 Clinical (unspecified phase)
0.5802 Remote Similarity NPD3818 Discontinued

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