Natural Product: NPC478566

Natural Product IDNPC478566
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 BLEHFVQPHJCOSJ-MRXNPFEDSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000145] Coumarins and derivatives
        • [CHEMONTID:0000358] Furanocoumarins
          • [CHEMONTID:0002569] Linear furanocoumarins
            • [CHEMONTID:0000202] Psoralens

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 BLEHFVQPHJCOSJ-MRXNPFEDSA-N
Standard InCHI InChI=1S/C21H22O6/c1-12(2)7-9-25-21-19-15(8-10-24-19)18(26-11-16(22)13(3)4)14-5-6-17(23)27-20(14)21/h5-8,10,16,22H,3,9,11H2,1-2,4H3/t16-/m1/s1
SMILES CC(=CCOc1c2c(cco2)c(c2ccc(=O)oc12)OC[C@H](C(=C)C)O)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   370.14 Volume:   377.752
?
Van der Waals volume.
Dense:   0.98 LogP:   3.765
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.34
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.635
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   7.0 Rigid Bonds:   18.0
TPSA:   82.04
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   1.0 Rings:   3.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.496 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.623 Fsp3:   0.286
MCE-18:   38.0
?
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:   0 PAINS Alert:   0
Colloidal aggregators:   0.647 Fluc inhibitor:   0.058
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.743
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.196
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.069 Promiscuous compounds:   0.124

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.784 MDCK Permeability:   -4.548
Pgp-inhibitor:   0.011 Pgp-substrate:   0.151
PAMPA:   0.285
?
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):   0.0
20% Bioavailability (F20%):   0.997 30% Bioavailability (F30%):   1.0
50% Bioavailability (F50%):   0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.156
Plasma Protein Binding (PPB):   85.206% Volume Distribution (VD):   0.0
Fu: 11.096%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   0.978 BCRP inhibitor:   0.948
BSEP inhibitor:   0.262

ADMET: Metabolism

CYP1A2-inhibitor:   0.034 CYP1A2-substrate:   0.734
CYP2C19-inhibitor:   0.704 CYP2C19-substrate:   0.859
CYP2C9-inhibitor:   0.003 CYP2C9-substrate:   0.898
CYP2D6-inhibitor:   0.018 CYP2D6-substrate:   0.98
CYP3A4-inhibitor:   0.862 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.929
HLM stability:   0.063
?
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):  10.484 Half-life (T1/2):  0.904

ADMET: Toxicity

hERG Blockers:  0.115 hERG Blockers (10um):  0.403
Human Hepatotoxicity (H-HT):  0.572 Drug-induced Liver Injury (DILI):  0.641
AMES Toxicity:  0.673 Rat Oral Acute Toxicity:  0.461
Maximum Recommended Daily Dose:  0.841 Skin Sensitization:  0.909
Carcinogencity:  0.718 Eye Corrosion:  0.001
Eye Irritation:  0.536 Respiratory Toxicity:  0.702
Drug-induced Neurotoxicity:  0.457 Ototoxicity:  0.499
Hematotoxicity:  0.436 Drug-induced Nephrotoxicity:  0.288
Genotoxicity:  0.984 RPMI-8226 Immunitoxicity:  0.06
A549 Cytotoxicity:  0.23 Hek293 Cytotoxicity:  0.341
BCF:   1.494
?
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:   4.168
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.981
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.423
?
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
NPO24758 Angelica dahurica Species Apiaceae Eukaryota n.a. root n.a. DOI[10.5012/bkcs.2003.24.11.1699]
NPO24758 Angelica dahurica Species Apiaceae Eukaryota n.a. root n.a. PMID[12510838]
NPO24758 Angelica dahurica Species Apiaceae Eukaryota n.a. root n.a. PMID[15646793]
NPO24758 Angelica dahurica Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[21625478]
NPO24758 Angelica dahurica Species Apiaceae Eukaryota n.a. root n.a. PMID[21657081]
NPO24758 Angelica dahurica Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[27444348]
NPO24758 Angelica dahurica Species Apiaceae Eukaryota Roots n.a. n.a. PMID[31464439]
NPO24758 Angelica dahurica Species Apiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO24758 Angelica dahurica Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO24758 Angelica dahurica Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO24758 Angelica dahurica Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO24758 Angelica dahurica Species Apiaceae 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
NPT65 Cell line HepG2 Homo sapiens Activity = 50.9 % PMID[31464439]
NPT65 Cell line HepG2 Homo sapiens Activity = 63.9 % PMID[31464439]

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 NPC478566 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
0.8525 High Similarity NPC478569
0.8421 Intermediate Similarity NPC155264
0.7966 Intermediate Similarity NPC210460
0.7937 Intermediate Similarity NPC478570
0.7833 Intermediate Similarity NPC107244
0.7667 Intermediate Similarity NPC67450
0.7385 Intermediate Similarity NPC478567
0.6912 Remote Similarity NPC193881
0.6462 Remote Similarity NPC224165
0.6418 Remote Similarity NPC198876
0.6154 Remote Similarity NPC169
0.6094 Remote Similarity NPC243509
0.6081 Remote Similarity NPC478568
0.6 Remote Similarity NPC215722
0.5833 Remote Similarity NPC234536
0.5758 Remote Similarity NPC88445
0.5735 Remote Similarity NPC144288
0.5616 Remote Similarity NPC53917
0.5467 Remote Similarity NPC269495
0.5342 Remote Similarity NPC216092
0.5195 Remote Similarity NPC49009
0.5067 Remote Similarity NPC191104
0.5063 Remote Similarity NPC14822

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC478566 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