Natural Product: NPC284743

Natural Product IDNPC284743
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 AQBZCCQCDWNNJQ-WMZHIEFXSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 92296469
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0002506] Isoflavonoids
        • [CHEMONTID:0001607] Rotenoids
          • [CHEMONTID:0003528] Rotenones

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 AQBZCCQCDWNNJQ-WMZHIEFXSA-N
Standard InCHI InChI=1S/C23H22O7/c1-22(2)8-7-12-15(30-22)6-5-13-20(12)29-19-11-28-16-10-18(27-4)17(26-3)9-14(16)23(19,25)21(13)24/h5-10,19,25H,11H2,1-4H3/t19-,23+/m0/s1
SMILES CC1(C)C=Cc2c(ccc3c2O[C@H]2COc4cc(c(cc4[C@@]2(C3=O)O)OC)OC)O1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   410.14 Volume:   404.022
?
Van der Waals volume.
Dense:   1.015 LogP:   2.358
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.474
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.443
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   27.0
TPSA:   83.45
?
Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   1.0 Rings:   5.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.814 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.853 Fsp3:   0.348
MCE-18:   101.0
?
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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.099 Fluc inhibitor:   0.304
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.531
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.478
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.207 Promiscuous compounds:   0.383

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.96 MDCK Permeability:   -4.738
Pgp-inhibitor:   0.149 Pgp-substrate:   0.041
PAMPA:   0.107
?
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):   0.002
20% Bioavailability (F20%):   0.296 30% Bioavailability (F30%):   0.29
50% Bioavailability (F50%):   0.975

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.324 MRP1:   0.644
Plasma Protein Binding (PPB):   95.243% Volume Distribution (VD):   0.312
Fu: 3.491%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.993
BSEP inhibitor:   0.995

ADMET: Metabolism

CYP1A2-inhibitor:   0.212 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.999 CYP2C19-substrate:   0.043
CYP2C9-inhibitor:   0.987 CYP2C9-substrate:   0.96
CYP2D6-inhibitor:   0.052 CYP2D6-substrate:   0.937
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   0.771
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.992
HLM stability:   0.909
?
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):  8.026 Half-life (T1/2):  2.298

ADMET: Toxicity

hERG Blockers:  0.149 hERG Blockers (10um):  0.432
Human Hepatotoxicity (H-HT):  0.796 Drug-induced Liver Injury (DILI):  0.375
AMES Toxicity:  0.722 Rat Oral Acute Toxicity:  0.81
Maximum Recommended Daily Dose:  0.575 Skin Sensitization:  0.891
Carcinogencity:  0.852 Eye Corrosion:  0.006
Eye Irritation:  0.762 Respiratory Toxicity:  0.819
Drug-induced Neurotoxicity:  0.675 Ototoxicity:  0.413
Hematotoxicity:  0.394 Drug-induced Nephrotoxicity:  0.692
Genotoxicity:  0.197 RPMI-8226 Immunitoxicity:  0.168
A549 Cytotoxicity:  0.274 Hek293 Cytotoxicity:  0.4
BCF:   1.617
?
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:   3.994
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.781
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.263
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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
NPO8274 Geijera parviflora Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[23848189]
NPO6485 Spiraea japonica Species Rosaceae Eukaryota n.a. n.a. n.a. PMID[24684844]
NPO4520 Allium macrostemon Species Amaryllidaceae Eukaryota n.a. leaf n.a. PMID[26434122]
NPO8274 Geijera parviflora Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO6485 Spiraea japonica Species Rosaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4520 Allium macrostemon Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4520 Allium macrostemon Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO6485 Spiraea japonica Species Rosaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO4520 Allium macrostemon Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO1007 Crotalaria paniculata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO6485 Spiraea japonica Species Rosaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO4520 Allium macrostemon Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO4520 Allium macrostemon Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1007 Crotalaria paniculata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6485 Spiraea japonica Species Rosaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8274 Geijera parviflora Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15101 Tricholoma panaeolum Species Tricholomataceae 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 NPC284743 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 NPC8965
0.8382 Intermediate Similarity NPC67302
0.8382 Intermediate Similarity NPC123696
0.7465 Intermediate Similarity NPC177480
0.6528 Remote Similarity NPC242395
0.6528 Remote Similarity NPC609259
0.6486 Remote Similarity NPC74559
0.6438 Remote Similarity NPC152477
0.6301 Remote Similarity NPC165549
0.6133 Remote Similarity NPC121333
0.6029 Remote Similarity NPC607486
0.5696 Remote Similarity NPC156635
0.5634 Remote Similarity NPC611309
0.5479 Remote Similarity NPC234052
0.52 Remote Similarity NPC603764
0.506 Remote Similarity NPC326877

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC284743 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