Natural Product: NPC4506

Natural Product IDNPC4506
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 XRKBRPFTFKKHEF-DGDBGZAXSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 5280406
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000476] Cinnamic acids and derivatives
        • [CHEMONTID:0001391] Hydroxycinnamic acids and derivatives
          • [CHEMONTID:0003002] Hydroxycinnamic acid esters
            • [CHEMONTID:0003003] Hydroxycinnamic acid glycosides

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 XRKBRPFTFKKHEF-DGDBGZAXSA-N
Standard InCHI InChI=1S/C17H22O10/c1-24-9-5-8(6-10(25-2)13(9)20)3-4-12(19)27-17-16(23)15(22)14(21)11(7-18)26-17/h3-6,11,14-18,20-23H,7H2,1-2H3/b4-3+/t11-,14-,15+,16-,17+/m1/s1
SMILES COc1cc(/C=C/C(=O)O[C@H]2[C@@H]([C@H]([C@@H]([C@@H](CO)O2)O)O)O)cc(c1O)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   386.12 Volume:   360.195
?
Van der Waals volume.
Dense:   1.072 LogP:   0.092
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   0.759
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.181
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   7.0 Rigid Bonds:   14.0
TPSA:   155.14
?
Topological Polar Surface Area.
 H-Bond Acceptor:   10.0
H-Bond Donor:   5.0 Rings:   2.0
Heavy Atoms:   10.0

MedChem Properties

QED Drug-Likeness Score:   0.296 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.68 Fsp3:   0.471
MCE-18:   54.4
?
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:   0.645 Fluc inhibitor:   0.681
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.194
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.223
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.232 Promiscuous compounds:   0.337

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.091 MDCK Permeability:   -5.291
Pgp-inhibitor:   0.054 Pgp-substrate:   0.266
PAMPA:   0.47
?
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):   0.866
20% Bioavailability (F20%):   0.385 30% Bioavailability (F30%):   0.982
50% Bioavailability (F50%):   0.986

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.014 MRP1:   0.386
Plasma Protein Binding (PPB):   73.709% Volume Distribution (VD):   -0.367
Fu: 26.632%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.713
BSEP inhibitor:   0.086

ADMET: Metabolism

CYP1A2-inhibitor:   0.002 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.005 CYP2C19-substrate:   0.002
CYP2C9-inhibitor:   0.032 CYP2C9-substrate:   0.001
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.667
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.986
HLM stability:   0.095
?
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):  2.485 Half-life (T1/2):  2.885

ADMET: Toxicity

hERG Blockers:  0.023 hERG Blockers (10um):  0.149
Human Hepatotoxicity (H-HT):  0.591 Drug-induced Liver Injury (DILI):  0.786
AMES Toxicity:  0.889 Rat Oral Acute Toxicity:  0.03
Maximum Recommended Daily Dose:  0.046 Skin Sensitization:  0.997
Carcinogencity:  0.377 Eye Corrosion:  0.001
Eye Irritation:  0.397 Respiratory Toxicity:  0.025
Drug-induced Neurotoxicity:  0.094 Ototoxicity:  0.854
Hematotoxicity:  0.32 Drug-induced Nephrotoxicity:  0.848
Genotoxicity:  0.144 RPMI-8226 Immunitoxicity:  0.143
A549 Cytotoxicity:  0.224 Hek293 Cytotoxicity:  0.161
BCF:   0.358
?
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:   2.976
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.532
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.669
?
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
NPO28315 Jania rubens Species Corallinaceae Eukaryota n.a. n.a. n.a. PMID[11086730]
NPO7539 Raphanus sativus Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[24176362]
NPO7539 Raphanus sativus Species Brassicaceae Eukaryota seeds n.a. n.a. PMID[25466198]
NPO28667 Waltheria americana Species Malvaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7539 Raphanus sativus Species Brassicaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28540 Aglaia ignea Species Meliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28348 Filicium decipiens Species Sapindaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28389 Helianthopsis microphylla n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO28315 Jania rubens Species Corallinaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28506 Onobrychis kachetica Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7539 Raphanus sativus Species Brassicaceae Eukaryota Root n.a. n.a. Database[FooDB]
NPO7539 Raphanus sativus Species Brassicaceae Eukaryota Leaf n.a. n.a. Database[FooDB]
NPO7539 Raphanus sativus Species Brassicaceae Eukaryota n.a. n.a. Database[FooDB]
NPO7539 Raphanus sativus Species Brassicaceae Eukaryota Fruit n.a. n.a. Database[FooDB]
NPO7539 Raphanus sativus Species Brassicaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO28667 Waltheria americana Species Malvaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO7539 Raphanus sativus Species Brassicaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO28667 Waltheria americana Species Malvaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO28667 Waltheria americana Species Malvaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO7539 Raphanus sativus Species Brassicaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO7539 Raphanus sativus Species Brassicaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO7539 Raphanus sativus Species Brassicaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28667 Waltheria americana Species Malvaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28540 Aglaia ignea Species Meliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28389 Helianthopsis microphylla n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO28348 Filicium decipiens Species Sapindaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28506 Onobrychis kachetica Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28315 Jania rubens Species Corallinaceae 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 NPC4506 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
0.8036 Intermediate Similarity NPC157554
0.7321 Intermediate Similarity NPC132895
0.7077 Intermediate Similarity NPC297342
0.6786 Remote Similarity NPC11724
0.6667 Remote Similarity NPC232880
0.6613 Remote Similarity NPC202700
0.6032 Remote Similarity NPC307110
0.5921 Remote Similarity NPC476865
0.5882 Remote Similarity NPC58279
0.5867 Remote Similarity NPC90896
0.5862 Remote Similarity NPC470270
0.5781 Remote Similarity NPC100389
0.5763 Remote Similarity NPC107478
0.575 Remote Similarity NPC173343
0.5741 Remote Similarity NPC200014
0.5733 Remote Similarity NPC476869
0.5714 Remote Similarity NPC48315
0.5658 Remote Similarity NPC476868
0.5606 Remote Similarity NPC185778
0.56 Remote Similarity NPC472612
0.5513 Remote Similarity NPC289967
0.55 Remote Similarity NPC283839
0.5484 Remote Similarity NPC604356
0.5455 Remote Similarity NPC109275
0.5395 Remote Similarity NPC476864
0.5325 Remote Similarity NPC476866
0.5316 Remote Similarity NPC262182
0.5303 Remote Similarity NPC52097
0.5294 Remote Similarity NPC118385
0.5263 Remote Similarity NPC199928
0.5263 Remote Similarity NPC476867
0.5256 Remote Similarity NPC21516
0.5224 Remote Similarity NPC5262
0.519 Remote Similarity NPC186073
0.5139 Remote Similarity NPC195196
0.5128 Remote Similarity NPC226005
0.5079 Remote Similarity NPC49074
0.5075 Remote Similarity NPC470236
0.5067 Remote Similarity NPC469559
0.506 Remote Similarity NPC229548
0.5059 Remote Similarity NPC472611

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC4506 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