Natural Product: NPC301961

Natural Product IDNPC301961
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 ZMNZBIACDAJCIU-QLJPJBMISA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL452773
PubChem CID 10638973
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0002506] Isoflavonoids
        • [CHEMONTID:0002617] Furanoisoflavonoids
          • [CHEMONTID:0001608] Pterocarpans

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 ZMNZBIACDAJCIU-QLJPJBMISA-N
Standard InCHI InChI=1S/C17H14O6/c1-19-11-3-2-8-16-10(6-20-17(8)15(11)18)9-4-13-14(22-7-21-13)5-12(9)23-16/h2-5,10,16,18H,6-7H2,1H3/t10-,16-/m1/s1
SMILES COc1ccc2[C@@H]3[C@H](COc2c1O)c1cc2c(cc1O3)OCO2

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   314.08 Volume:   296.729
?
Van der Waals volume.
Dense:   1.058 LogP:   2.575
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.761
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.467
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   24.0
TPSA:   66.38
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   1.0 Rings:   5.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.873 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.474 Fsp3:   0.294
MCE-18:   84.091
?
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:   1 PAINS Alert:   0
Colloidal aggregators:   0.694 Fluc inhibitor:   0.851
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.343
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.14
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.288 Promiscuous compounds:   0.476

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.944 MDCK Permeability:   -4.717
Pgp-inhibitor:   0.197 Pgp-substrate:   0.037
PAMPA:   0.04
?
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):   0.002
20% Bioavailability (F20%):   0.078 30% Bioavailability (F30%):   0.01
50% Bioavailability (F50%):   0.668

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.92 MRP1:   0.693
Plasma Protein Binding (PPB):   92.228% Volume Distribution (VD):   -0.424
Fu: 7.856%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.985
OATP1B3 inhibitor:   0.974 BCRP inhibitor:   0.25
BSEP inhibitor:   0.971

ADMET: Metabolism

CYP1A2-inhibitor:   0.997 CYP1A2-substrate:   0.998
CYP2C19-inhibitor:   0.984 CYP2C19-substrate:   0.785
CYP2C9-inhibitor:   0.998 CYP2C9-substrate:   0.987
CYP2D6-inhibitor:   0.988 CYP2D6-substrate:   0.998
CYP3A4-inhibitor:   0.83 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.039 CYP2C8-inhibitor:   0.034
HLM stability:   0.803
?
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):  4.086 Half-life (T1/2):  2.767

ADMET: Toxicity

hERG Blockers:  0.195 hERG Blockers (10um):  0.549
Human Hepatotoxicity (H-HT):  0.625 Drug-induced Liver Injury (DILI):  0.877
AMES Toxicity:  0.643 Rat Oral Acute Toxicity:  0.39
Maximum Recommended Daily Dose:  0.456 Skin Sensitization:  0.512
Carcinogencity:  0.789 Eye Corrosion:  0.027
Eye Irritation:  0.94 Respiratory Toxicity:  0.648
Drug-induced Neurotoxicity:  0.457 Ototoxicity:  0.462
Hematotoxicity:  0.472 Drug-induced Nephrotoxicity:  0.496
Genotoxicity:  0.236 RPMI-8226 Immunitoxicity:  0.125
A549 Cytotoxicity:  0.283 Hek293 Cytotoxicity:  0.464
BCF:   1.295
?
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:   3.644
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.858
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.674
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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
NPO13784 Dalbergia candenatensis Species Fabaceae Eukaryota heartwood n.a. n.a. PMID[19653666]
NPO13784 Dalbergia candenatensis Species Fabaceae Eukaryota n.a. Thai n.a. PMID[3430167]
NPO13784 Dalbergia candenatensis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13784 Dalbergia candenatensis Species 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
NPT91 Cell line KB Homo sapiens ED50 = 4.0 ug ml-1 PMID[20392109]

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 NPC301961 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 NPC71288
0.7458 Intermediate Similarity NPC605383
0.6949 Remote Similarity NPC80326
0.6949 Remote Similarity NPC309124
0.6833 Remote Similarity NPC300798
0.6833 Remote Similarity NPC58137
0.6825 Remote Similarity NPC166584
0.6452 Remote Similarity NPC474749
0.6452 Remote Similarity NPC226540
0.6349 Remote Similarity NPC178014
0.6349 Remote Similarity NPC42716
0.6349 Remote Similarity NPC11422
0.5479 Remote Similarity NPC609291
0.5469 Remote Similarity NPC27495
0.5417 Remote Similarity NPC71726
0.5385 Remote Similarity NPC232164
0.5385 Remote Similarity NPC473739
0.5263 Remote Similarity NPC159922
0.5256 Remote Similarity NPC238140
0.5075 Remote Similarity NPC236306

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC301961 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