Natural Product: NPC264862

Natural Product IDNPC264862
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 NZVLHOXXOSELRF-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 5488618
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:0003651] 3'-hydroxy,4'-methoxyisoflavonoids

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 NZVLHOXXOSELRF-UHFFFAOYSA-N
Standard InCHI InChI=1S/C16H12O7/c1-22-16-11(19)2-7(3-12(16)20)9-6-23-13-5-8(17)4-10(18)14(13)15(9)21/h2-6,17-20H,1H3
SMILES COc1c(cc(cc1O)c1coc2cc(cc(c2c1=O)O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   316.06 Volume:   300.063
?
Van der Waals volume.
Dense:   1.053 LogP:   1.249
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.539
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.038
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   18.0
TPSA:   120.36
?
Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   4.0 Rings:   3.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.572 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.675 Fsp3:   0.062
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:   Rejected GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   1 PAINS Alert:   0
Colloidal aggregators:   0.741 Fluc inhibitor:   0.613
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.953
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.544
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.552 Promiscuous compounds:   0.909

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.175 MDCK Permeability:   -4.858
Pgp-inhibitor:   0.001 Pgp-substrate:   0.34
PAMPA:   0.516
?
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):   0.001
20% Bioavailability (F20%):   0.174 30% Bioavailability (F30%):   0.729
50% Bioavailability (F50%):   0.987

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.009 MRP1:   0.445
Plasma Protein Binding (PPB):   93.514% Volume Distribution (VD):   -0.644
Fu: 5.226%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.864
OATP1B3 inhibitor:   0.962 BCRP inhibitor:   0.893
BSEP inhibitor:   0.058

ADMET: Metabolism

CYP1A2-inhibitor:   0.997 CYP1A2-substrate:   0.191
CYP2C19-inhibitor:   0.035 CYP2C19-substrate:   0.042
CYP2C9-inhibitor:   0.999 CYP2C9-substrate:   0.824
CYP2D6-inhibitor:   0.999 CYP2D6-substrate:   0.432
CYP3A4-inhibitor:   0.064 CYP3A4-substrate:   0.025
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.976
?
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):  3.886 Half-life (T1/2):  1.45

ADMET: Toxicity

hERG Blockers:  0.099 hERG Blockers (10um):  0.561
Human Hepatotoxicity (H-HT):  0.466 Drug-induced Liver Injury (DILI):  0.877
AMES Toxicity:  0.589 Rat Oral Acute Toxicity:  0.58
Maximum Recommended Daily Dose:  0.843 Skin Sensitization:  0.635
Carcinogencity:  0.626 Eye Corrosion:  0.026
Eye Irritation:  0.991 Respiratory Toxicity:  0.864
Drug-induced Neurotoxicity:  0.093 Ototoxicity:  0.201
Hematotoxicity:  0.088 Drug-induced Nephrotoxicity:  0.111
Genotoxicity:  0.962 RPMI-8226 Immunitoxicity:  0.097
A549 Cytotoxicity:  0.491 Hek293 Cytotoxicity:  0.635
BCF:   0.942
?
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:   3.543
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.461
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.817
?
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
NPO1859 Lantana camara Species Verbenaceae Eukaryota aerial parts n.a. n.a. PMID[10869197]
NPO1859 Lantana camara Species Verbenaceae Eukaryota n.a. n.a. n.a. PMID[1812212]
NPO1859 Lantana camara Species Verbenaceae Eukaryota n.a. n.a. n.a. PMID[33780581]
NPO1859 Lantana camara Species Verbenaceae Eukaryota n.a. n.a. n.a. PMID[36270431]
NPO1859 Lantana camara Species Verbenaceae Eukaryota n.a. n.a. n.a. PMID[38257257]
NPO1859 Lantana camara Species Verbenaceae Eukaryota n.a. n.a. n.a. PMID[38893531]
NPO1859 Lantana camara Species Verbenaceae Eukaryota n.a. n.a. n.a. PMID[39104562]
NPO1859 Lantana camara Species Verbenaceae Eukaryota leaves n.a. n.a. PMID[9834145]
NPO942 Perophora namei Species Perophoridae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3733 Senecio triangularis Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1859 Lantana camara Species Verbenaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1859 Lantana camara Species Verbenaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO1859 Lantana camara Species Verbenaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO2781 Iris kumaonensis Species Tarachodidae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO1859 Lantana camara Species Verbenaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO2566 Nocardiopsaceae Species Nocardiopsaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO6516 Aspidosperma megalocarpon Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3733 Senecio triangularis Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1859 Lantana camara Species Verbenaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5561 Thenea muricata Species Theneidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO942 Perophora namei Species Perophoridae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2781 Iris kumaonensis Species Tarachodidae 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 NPC264862 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
0.7963 Intermediate Similarity NPC194653
0.7963 Intermediate Similarity NPC481044
0.7547 Intermediate Similarity NPC78341
0.7407 Intermediate Similarity NPC294409
0.7407 Intermediate Similarity NPC490701
0.74 Intermediate Similarity NPC193792
0.7193 Intermediate Similarity NPC254702
0.7143 Intermediate Similarity NPC200316
0.6964 Remote Similarity NPC19980
0.6964 Remote Similarity NPC239363
0.6935 Remote Similarity NPC128774
0.6897 Remote Similarity NPC264550
0.6897 Remote Similarity NPC45291
0.6719 Remote Similarity NPC482075
0.6667 Remote Similarity NPC38065
0.661 Remote Similarity NPC483637
0.6604 Remote Similarity NPC39426
0.6604 Remote Similarity NPC608554
0.6552 Remote Similarity NPC309154
0.6441 Remote Similarity NPC279668
0.6441 Remote Similarity NPC278323
0.6333 Remote Similarity NPC142876
0.625 Remote Similarity NPC233918
0.625 Remote Similarity NPC268059
0.623 Remote Similarity NPC104728
0.6212 Remote Similarity NPC74178
0.6154 Remote Similarity NPC479305
0.6129 Remote Similarity NPC167595
0.6119 Remote Similarity NPC52889
0.6102 Remote Similarity NPC250557
0.6102 Remote Similarity NPC209487
0.6034 Remote Similarity NPC269451
0.5932 Remote Similarity NPC245382
0.5789 Remote Similarity NPC87545
0.5781 Remote Similarity NPC238279
0.5763 Remote Similarity NPC35763
0.5763 Remote Similarity NPC131266
0.5672 Remote Similarity NPC280937
0.5593 Remote Similarity NPC123886
0.5588 Remote Similarity NPC474052
0.5507 Remote Similarity NPC107838
0.55 Remote Similarity NPC50403
0.55 Remote Similarity NPC601901
0.5455 Remote Similarity NPC213659
0.5455 Remote Similarity NPC326109
0.541 Remote Similarity NPC303644
0.5397 Remote Similarity NPC80710
0.5373 Remote Similarity NPC606200
0.5333 Remote Similarity NPC481043
0.5312 Remote Similarity NPC476055
0.5303 Remote Similarity NPC608523
0.5294 Remote Similarity NPC475705
0.5246 Remote Similarity NPC116632
0.5152 Remote Similarity NPC93552
0.5139 Remote Similarity NPC474960
0.5135 Remote Similarity NPC156457
0.5079 Remote Similarity NPC181209
0.5079 Remote Similarity NPC605826
0.5077 Remote Similarity NPC114192
0.507 Remote Similarity NPC231763
0.507 Remote Similarity NPC303197

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC264862 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
0.6604 Remote Similarity NPD1510 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