Natural Product: NPC68882

Natural Product IDNPC68882
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 maximaisoflavone B
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 44257236
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 FNMKZDDKPDBYJM-UHFFFAOYSA-N
Standard InCHI InChI=1S/C21H18O5/c1-13(2)7-8-23-15-4-5-16-19(10-15)24-11-17(21(16)22)14-3-6-18-20(9-14)26-12-25-18/h3-7,9-11H,8,12H2,1-2H3
SMILES CC(=CCOc1ccc2c(c1)occ(c2=O)c1ccc2c(c1)OCO2)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   350.12 Volume:   357.769
?
Van der Waals volume.
Dense:   0.979 LogP:   4.288
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.627
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.257
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   23.0
TPSA:   57.9
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   0.0 Rings:   4.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.647 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.448 Fsp3:   0.19
MCE-18:   43.68
?
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:   0.9 Fluc inhibitor:   0.992
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.961
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.645
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.306 Promiscuous compounds:   0.151

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.712 MDCK Permeability:   -4.643
Pgp-inhibitor:   0.792 Pgp-substrate:   0.008
PAMPA:   0.451
?
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):   0.005
20% Bioavailability (F20%):   0.029 30% Bioavailability (F30%):   0.007
50% Bioavailability (F50%):   0.504

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.211 MRP1:   0.732
Plasma Protein Binding (PPB):   96.59% Volume Distribution (VD):   0.097
Fu: 3.109%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.907
OATP1B3 inhibitor:   0.996 BCRP inhibitor:   0.47
BSEP inhibitor:   0.998

ADMET: Metabolism

CYP1A2-inhibitor:   0.991 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.315 CYP2C19-substrate:   0.925
CYP2C9-inhibitor:   0.995 CYP2C9-substrate:   1.0
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.983
CYP3A4-inhibitor:   0.001 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.674 CYP2C8-inhibitor:   0.504
HLM stability:   0.59
?
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):  4.476 Half-life (T1/2):  0.743

ADMET: Toxicity

hERG Blockers:  0.429 hERG Blockers (10um):  0.664
Human Hepatotoxicity (H-HT):  0.626 Drug-induced Liver Injury (DILI):  0.919
AMES Toxicity:  0.641 Rat Oral Acute Toxicity:  0.449
Maximum Recommended Daily Dose:  0.67 Skin Sensitization:  0.378
Carcinogencity:  0.891 Eye Corrosion:  0.006
Eye Irritation:  0.787 Respiratory Toxicity:  0.742
Drug-induced Neurotoxicity:  0.482 Ototoxicity:  0.339
Hematotoxicity:  0.445 Drug-induced Nephrotoxicity:  0.424
Genotoxicity:  0.573 RPMI-8226 Immunitoxicity:  0.102
A549 Cytotoxicity:  0.15 Hek293 Cytotoxicity:  0.397
BCF:   1.951
?
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:   4.577
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.234
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.739
?
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]
NPO33696 Millettia oblata ssp. teitensis Species Fabaceae Eukaryota leaves Ngangao Forest, Taita Hill, Taita County, Kenya 2014-JUL PMID[28665590]
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

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 NPC68882 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
0.8226 Intermediate Similarity NPC185401
0.7705 Intermediate Similarity NPC602183
0.75 Intermediate Similarity NPC607700
0.746 Intermediate Similarity NPC254741
0.7097 Intermediate Similarity NPC471590
0.6349 Remote Similarity NPC185607
0.6308 Remote Similarity NPC148497
0.5942 Remote Similarity NPC35544
0.5875 Remote Similarity NPC601607
0.5844 Remote Similarity NPC478528
0.5811 Remote Similarity NPC488570
0.5797 Remote Similarity NPC153008
0.5625 Remote Similarity NPC182428
0.5571 Remote Similarity NPC603384
0.5556 Remote Similarity NPC260640
0.5522 Remote Similarity NPC479067
0.55 Remote Similarity NPC5840
0.5467 Remote Similarity NPC113055
0.5441 Remote Similarity NPC136095
0.5417 Remote Similarity NPC13967
0.5342 Remote Similarity NPC203636
0.5325 Remote Similarity NPC605424
0.5278 Remote Similarity NPC104728
0.5278 Remote Similarity NPC478213
0.5263 Remote Similarity NPC479305
0.5211 Remote Similarity NPC602689
0.52 Remote Similarity NPC249824
0.52 Remote Similarity NPC133400
0.5195 Remote Similarity NPC608710
0.5075 Remote Similarity NPC195919
0.5072 Remote Similarity NPC216314

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC68882 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
0.5522 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