Natural Product: NPC203636

Natural Product IDNPC203636
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 QKBHQLLFELAADR-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 101855821
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0002506] Isoflavonoids
        • [CHEMONTID:0002901] Isoflav-2-enes
          • [CHEMONTID:0000494] Isoflavones

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 QKBHQLLFELAADR-UHFFFAOYSA-N
Standard InCHI InChI=1S/C25H26O5/c1-16(2)9-11-28-19-7-5-18(6-8-19)21-15-30-23-14-20(29-12-10-17(3)4)13-22(26)24(23)25(21)27/h5-10,13-15,26H,11-12H2,1-4H3
SMILES CC(=CCOc1ccc(cc1)c1coc2cc(cc(c2c1=O)O)OCC=C(C)C)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   406.18 Volume:   432.873
?
Van der Waals volume.
Dense:   0.938 LogP:   5.65
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.95
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.572
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   7.0 Rigid Bonds:   20.0
TPSA:   68.9
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   1.0 Rings:   3.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.498 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.699 Fsp3:   0.24
MCE-18:   19.0
?
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:   0.991 Fluc inhibitor:   0.829
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.936
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.728
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.332 Promiscuous compounds:   0.149

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.669 MDCK Permeability:   -4.62
Pgp-inhibitor:   0.736 Pgp-substrate:   0.136
PAMPA:   0.461
?
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):   0.075
20% Bioavailability (F20%):   0.169 30% Bioavailability (F30%):   0.573
50% Bioavailability (F50%):   0.807

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.065 MRP1:   0.883
Plasma Protein Binding (PPB):   96.493% Volume Distribution (VD):   0.098
Fu: 3.032%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.519
OATP1B3 inhibitor:   0.897 BCRP inhibitor:   0.962
BSEP inhibitor:   0.93

ADMET: Metabolism

CYP1A2-inhibitor:   0.995 CYP1A2-substrate:   0.998
CYP2C19-inhibitor:   0.103 CYP2C19-substrate:   0.415
CYP2C9-inhibitor:   0.995 CYP2C9-substrate:   0.77
CYP2D6-inhibitor:   0.999 CYP2D6-substrate:   0.064
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.999
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.973
?
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):  7.23 Half-life (T1/2):  0.814

ADMET: Toxicity

hERG Blockers:  0.463 hERG Blockers (10um):  0.732
Human Hepatotoxicity (H-HT):  0.634 Drug-induced Liver Injury (DILI):  0.945
AMES Toxicity:  0.55 Rat Oral Acute Toxicity:  0.333
Maximum Recommended Daily Dose:  0.513 Skin Sensitization:  0.689
Carcinogencity:  0.692 Eye Corrosion:  0.0
Eye Irritation:  0.563 Respiratory Toxicity:  0.836
Drug-induced Neurotoxicity:  0.216 Ototoxicity:  0.427
Hematotoxicity:  0.324 Drug-induced Nephrotoxicity:  0.402
Genotoxicity:  0.524 RPMI-8226 Immunitoxicity:  0.068
A549 Cytotoxicity:  0.202 Hek293 Cytotoxicity:  0.32
BCF:   2.116
?
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:   4.935
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.432
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   6.014
?
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
NPO40204 Millettia extensa Species Fabaceae Eukaryota Stems n.a. n.a. PMID[30106294]
NPO40204 Millettia extensa Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[31403786]

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
NPT113 Cell line RAW264.7 Mus musculus Activity = 72.2 % PMID[31403786]
NPT566 Organism Salmonella typhimurium Salmonella enterica subsp. enterica serovar Typhimurium MIC = 128.0 ug.mL-1 PMID[31403786]
NPT2909 Organism Shigella flexneri Shigella flexneri MIC = 128.0 ug.mL-1 PMID[31403786]
NPT17 Organism Staphylococcus epidermidis Staphylococcus epidermidis MIC = 128.0 ug.mL-1 PMID[31403786]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC = 128.0 ug.mL-1 PMID[31403786]

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 NPC203636 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
0.9298 High Similarity NPC249824
0.9298 High Similarity NPC133400
0.8226 Intermediate Similarity NPC488570
0.7241 Intermediate Similarity NPC116632
0.662 Remote Similarity NPC233502
0.6308 Remote Similarity NPC254741
0.6301 Remote Similarity NPC604503
0.629 Remote Similarity NPC303644
0.6232 Remote Similarity NPC479305
0.5811 Remote Similarity NPC160515
0.5781 Remote Similarity NPC294409
0.5781 Remote Similarity NPC490701
0.5672 Remote Similarity NPC114192
0.5658 Remote Similarity NPC487213
0.5641 Remote Similarity NPC113475
0.5571 Remote Similarity NPC185401
0.5385 Remote Similarity NPC35763
0.5385 Remote Similarity NPC73511
0.5333 Remote Similarity NPC469404
0.5325 Remote Similarity NPC229847
0.5294 Remote Similarity NPC90665
0.5278 Remote Similarity NPC40942
0.5135 Remote Similarity NPC280937
0.5128 Remote Similarity NPC478528
0.5128 Remote Similarity NPC348541
0.5119 Remote Similarity NPC487212
0.5072 Remote Similarity NPC278323
0.507 Remote Similarity NPC13967
0.5067 Remote Similarity NPC253822
0.5067 Remote Similarity NPC608710

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC203636 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