Natural Product: NPC185401

Natural Product IDNPC185401
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 HSZOZDPOYZAYTH-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 1757897
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0002506] Isoflavonoids
        • [CHEMONTID:0002586] O-methylated isoflavonoids
          • [CHEMONTID:0002606] 4'-O-methylated isoflavonoids
            • [CHEMONTID:0002687] 4'-O-methylisoflavones

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 HSZOZDPOYZAYTH-UHFFFAOYSA-N
Standard InCHI InChI=1S/C22H22O5/c1-14(2)9-10-26-16-6-7-17-20(12-16)27-13-18(22(17)23)15-5-8-19(24-3)21(11-15)25-4/h5-9,11-13H,10H2,1-4H3
SMILES CC(=CCOc1ccc2c(c1)occ(c1ccc(c(c1)OC)OC)c2=O)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   366.15 Volume:   383.622
?
Van der Waals volume.
Dense:   0.954 LogP:   3.888
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.537
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.336
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The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   19.0
TPSA:   57.9
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   0.0 Rings:   3.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.585 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.303 Fsp3:   0.227
MCE-18:   18.0
?
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:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.778 Fluc inhibitor:   0.95
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.928
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.556
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.346 Promiscuous compounds:   0.124

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.642 MDCK Permeability:   -4.613
Pgp-inhibitor:   0.924 Pgp-substrate:   0.115
PAMPA:   0.225
?
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):   0.288
20% Bioavailability (F20%):   0.081 30% Bioavailability (F30%):   0.325
50% Bioavailability (F50%):   0.792

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.004 MRP1:   0.898
Plasma Protein Binding (PPB):   95.319% Volume Distribution (VD):   0.198
Fu: 3.86%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.968
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.951
BSEP inhibitor:   0.989

ADMET: Metabolism

CYP1A2-inhibitor:   0.972 CYP1A2-substrate:   0.999
CYP2C19-inhibitor:   0.705 CYP2C19-substrate:   0.982
CYP2C9-inhibitor:   0.984 CYP2C9-substrate:   0.078
CYP2D6-inhibitor:   0.999 CYP2D6-substrate:   0.137
CYP3A4-inhibitor:   0.202 CYP3A4-substrate:   0.992
CYP2B6-substrate:   0.305 CYP2C8-inhibitor:   0.96
HLM stability:   0.8
?
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):  7.596 Half-life (T1/2):  1.2

ADMET: Toxicity

hERG Blockers:  0.383 hERG Blockers (10um):  0.665
Human Hepatotoxicity (H-HT):  0.594 Drug-induced Liver Injury (DILI):  0.853
AMES Toxicity:  0.553 Rat Oral Acute Toxicity:  0.425
Maximum Recommended Daily Dose:  0.569 Skin Sensitization:  0.39
Carcinogencity:  0.81 Eye Corrosion:  0.014
Eye Irritation:  0.819 Respiratory Toxicity:  0.788
Drug-induced Neurotoxicity:  0.504 Ototoxicity:  0.352
Hematotoxicity:  0.452 Drug-induced Nephrotoxicity:  0.397
Genotoxicity:  0.267 RPMI-8226 Immunitoxicity:  0.096
A549 Cytotoxicity:  0.119 Hek293 Cytotoxicity:  0.31
BCF:   1.932
?
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:   4.49
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.887
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.384
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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
NPO30165 Pongamia pinnata Species Fabaceae Eukaryota stem bark Indonesia 1999-SEP PMID[14510596]
NPO30165 Pongamia pinnata Species Fabaceae Eukaryota n.a. stem n.a. PMID[14510596]
NPO30165 Pongamia pinnata Species Fabaceae Eukaryota dry stem n.a. n.a. PMID[25466192]
NPO30165 Pongamia pinnata Species Fabaceae Eukaryota Roots n.a. n.a. PMID[29482940]
NPO30165 Pongamia pinnata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO30165 Pongamia pinnata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]

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
NPT34 Cell line BV-2 Mus musculus IC50 = 36900.0 nM PMID[29482940]

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 NPC185401 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
0.8448 Intermediate Similarity NPC254741
0.7857 Intermediate Similarity NPC185607
0.7759 Intermediate Similarity NPC471590
0.7015 Intermediate Similarity NPC488570
0.6812 Remote Similarity NPC607700
0.6667 Remote Similarity NPC602183
0.6528 Remote Similarity NPC478528
0.6441 Remote Similarity NPC182428
0.6351 Remote Similarity NPC5840
0.6333 Remote Similarity NPC195919
0.619 Remote Similarity NPC136095
0.6143 Remote Similarity NPC479305
0.6119 Remote Similarity NPC13967
0.6032 Remote Similarity NPC216314
0.5857 Remote Similarity NPC249824
0.5857 Remote Similarity NPC133400
0.5781 Remote Similarity NPC479067
0.5758 Remote Similarity NPC12377
0.5714 Remote Similarity NPC189270
0.5692 Remote Similarity NPC181124
0.5571 Remote Similarity NPC203636
0.5397 Remote Similarity NPC120924
0.5373 Remote Similarity NPC148497
0.5256 Remote Similarity NPC229847
0.5224 Remote Similarity NPC186507
0.5217 Remote Similarity NPC602689
0.52 Remote Similarity NPC608710
0.5143 Remote Similarity NPC153008
0.5072 Remote Similarity NPC200316
0.507 Remote Similarity NPC478213
0.5062 Remote Similarity NPC78071

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC185401 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
0.5781 Remote Similarity NPD2796 Phase 2

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