Natural Product: NPC473077

Natural Product IDNPC473077
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 YRFONVUVHGLFMJ-OAQYLSRUSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL3609151
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0000337] Flavans
          • [CHEMONTID:0003642] 8-prenylated flavans
            • [CHEMONTID:0003508] 8-prenylated flavanones

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 YRFONVUVHGLFMJ-OAQYLSRUSA-N
Standard InCHI InChI=1S/C25H28O7/c1-24(2,30)7-6-14-16(26)10-18(28)22-19(29)12-21(31-23(14)22)15-9-13-5-8-25(3,4)32-20(13)11-17(15)27/h5,8-11,21,26-28,30H,6-7,12H2,1-4H3/t21-/m1/s1
SMILES CC1(C=CC2=CC(=C(C=C2O1)O)C3CC(=O)C4=C(C=C(C(=C4O3)CCC(C)(C)O)O)O)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   440.18 Volume:   447.17
?
Van der Waals volume.
Dense:   0.984 LogP:   3.35
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.049
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.325
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   23.0
TPSA:   116.45
?
Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   4.0 Rings:   4.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.557 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.853 Fsp3:   0.4
MCE-18:   91.971
?
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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.58 Fluc inhibitor:   0.173
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.898
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.795
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.129 Promiscuous compounds:   0.12

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.113 MDCK Permeability:   -4.778
Pgp-inhibitor:   0.555 Pgp-substrate:   0.024
PAMPA:   0.118
?
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%):   0.143 30% Bioavailability (F30%):   0.903
50% Bioavailability (F50%):   0.998

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.142 MRP1:   0.96
Plasma Protein Binding (PPB):   96.492% Volume Distribution (VD):   0.309
Fu: 3.493%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.99
OATP1B3 inhibitor:   0.903 BCRP inhibitor:   0.984
BSEP inhibitor:   0.999

ADMET: Metabolism

CYP1A2-inhibitor:   0.136 CYP1A2-substrate:   0.999
CYP2C19-inhibitor:   0.145 CYP2C19-substrate:   0.138
CYP2C9-inhibitor:   0.84 CYP2C9-substrate:   0.002
CYP2D6-inhibitor:   0.004 CYP2D6-substrate:   0.329
CYP3A4-inhibitor:   0.053 CYP3A4-substrate:   0.057
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.808
?
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):  2.451 Half-life (T1/2):  1.616

ADMET: Toxicity

hERG Blockers:  0.074 hERG Blockers (10um):  0.517
Human Hepatotoxicity (H-HT):  0.698 Drug-induced Liver Injury (DILI):  0.223
AMES Toxicity:  0.744 Rat Oral Acute Toxicity:  0.556
Maximum Recommended Daily Dose:  0.707 Skin Sensitization:  0.798
Carcinogencity:  0.781 Eye Corrosion:  0.0
Eye Irritation:  0.681 Respiratory Toxicity:  0.915
Drug-induced Neurotoxicity:  0.047 Ototoxicity:  0.772
Hematotoxicity:  0.187 Drug-induced Nephrotoxicity:  0.594
Genotoxicity:  0.82 RPMI-8226 Immunitoxicity:  0.242
A549 Cytotoxicity:  0.238 Hek293 Cytotoxicity:  0.579
BCF:   1.336
?
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:   3.832
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.666
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.627
?
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
NPO30804 Cudrania tricuspidata Species Moraceae Eukaryota n.a. n.a. n.a. PMID[15787460]
NPO30804 Cudrania tricuspidata Species Moraceae Eukaryota n.a. root n.a. PMID[15787460]
NPO30804 Cudrania tricuspidata Species Moraceae Eukaryota n.a. n.a. n.a. PMID[16203143]
NPO30804 Cudrania tricuspidata Species Moraceae Eukaryota n.a. n.a. n.a. PMID[16919944]
NPO30804 Cudrania tricuspidata Species Moraceae Eukaryota root bark n.a. n.a. PMID[17608532]
NPO30804 Cudrania tricuspidata Species Moraceae Eukaryota n.a. n.a. n.a. PMID[17950599]
NPO30804 Cudrania tricuspidata Species Moraceae Eukaryota fruits n.a. n.a. PMID[19113968]
NPO30804 Cudrania tricuspidata Species Moraceae Eukaryota Roots n.a. n.a. PMID[19191562]
NPO30804 Cudrania tricuspidata Species Moraceae Eukaryota n.a. root n.a. PMID[19280148]
NPO30804 Cudrania tricuspidata Species Moraceae Eukaryota n.a. n.a. n.a. PMID[19285413]
NPO30804 Cudrania tricuspidata Species Moraceae Eukaryota n.a. n.a. n.a. PMID[19660948]
NPO30804 Cudrania tricuspidata Species Moraceae Eukaryota n.a. root n.a. PMID[21319773]
NPO30804 Cudrania tricuspidata Species Moraceae Eukaryota Roots n.a. n.a. PMID[25322455]
NPO30804 Cudrania tricuspidata Species Moraceae Eukaryota root barks purchased from the local herbal market, Chungbuk, Korea 2012-JUL PMID[26227773]
NPO30804 Cudrania tricuspidata Species Moraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO30804 Cudrania tricuspidata Species Moraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO30804 Cudrania tricuspidata Species Moraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]

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
NPT1120 Individual protein Pancreatic triacylglycerol lipase Sus scrofa IC50 = 84600.0 nM DOI[10.1007/s00044-011-9628-y]
NPT1120 Individual protein Pancreatic triacylglycerol lipase Sus scrofa Inhibition = 52.0 % PMID[12444683]

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 NPC473077 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
1.0 High Similarity NPC296998
0.6623 Remote Similarity NPC283234
0.6104 Remote Similarity NPC267375
0.5775 Remote Similarity NPC480991
0.5422 Remote Similarity NPC218226
0.5256 Remote Similarity NPC312973
0.5181 Remote Similarity NPC54577
0.5132 Remote Similarity NPC176229

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC473077 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