Natural Product: NPC602963

Natural Product IDNPC602963
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 RBVYFSLWUBLPMG-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL495722
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]

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 RBVYFSLWUBLPMG-UHFFFAOYSA-N
Standard InCHI InChI=1S/C17H14O6/c1-21-16-13(19)12-10(18)8-11(9-6-4-3-5-7-9)23-15(12)17(22-2)14(16)20/h3-8,19-20H,1-2H3
SMILES COc1c(O)c(OC)c2oc(-c3ccccc3)cc(=O)c2c1O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   314.08 Volume:   308.569
?
Van der Waals volume.
Dense:   1.018 LogP:   3.055
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.705
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.263
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   18.0
TPSA:   89.13
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   2.0 Rings:   3.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.772 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.399 Fsp3:   0.118
MCE-18:   18.0
?
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:   0.315 Fluc inhibitor:   0.503
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.705
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.584
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.332 Promiscuous compounds:   0.841

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.966 MDCK Permeability:   -4.752
Pgp-inhibitor:   0.946 Pgp-substrate:   0.109
PAMPA:   0.126
?
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%):   0.031 30% Bioavailability (F30%):   0.29
50% Bioavailability (F50%):   0.654

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.863 MRP1:   0.965
Plasma Protein Binding (PPB):   98.49% Volume Distribution (VD):   -0.537
Fu: 0.728%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.813
OATP1B3 inhibitor:   0.928 BCRP inhibitor:   0.766
BSEP inhibitor:   0.966

ADMET: Metabolism

CYP1A2-inhibitor:   0.508 CYP1A2-substrate:   0.904
CYP2C19-inhibitor:   0.016 CYP2C19-substrate:   0.106
CYP2C9-inhibitor:   0.64 CYP2C9-substrate:   0.01
CYP2D6-inhibitor:   0.861 CYP2D6-substrate:   0.229
CYP3A4-inhibitor:   0.159 CYP3A4-substrate:   0.567
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.977
HLM stability:   0.832
?
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):  3.284 Half-life (T1/2):  1.254

ADMET: Toxicity

hERG Blockers:  0.117 hERG Blockers (10um):  0.533
Human Hepatotoxicity (H-HT):  0.488 Drug-induced Liver Injury (DILI):  0.845
AMES Toxicity:  0.441 Rat Oral Acute Toxicity:  0.436
Maximum Recommended Daily Dose:  0.476 Skin Sensitization:  0.724
Carcinogencity:  0.677 Eye Corrosion:  0.247
Eye Irritation:  0.961 Respiratory Toxicity:  0.619
Drug-induced Neurotoxicity:  0.229 Ototoxicity:  0.155
Hematotoxicity:  0.256 Drug-induced Nephrotoxicity:  0.132
Genotoxicity:  0.492 RPMI-8226 Immunitoxicity:  0.056
A549 Cytotoxicity:  0.232 Hek293 Cytotoxicity:  0.364
BCF:   1.044
?
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:   3.862
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.689
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.32
?
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
NPO5855 Scutellaria repens Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5855 Scutellaria repens Species Lamiaceae 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
NPT28438 Unchecked Unchecked n.a. logKi = -0.699 n.a. PMID[18158201]

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 NPC602963 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
0.8163 Intermediate Similarity NPC274327
0.8163 Intermediate Similarity NPC275836
0.75 Intermediate Similarity NPC600155
0.7358 Intermediate Similarity NPC183597
0.7358 Intermediate Similarity NPC146165
0.7255 Intermediate Similarity NPC131624
0.7222 Intermediate Similarity NPC4455
0.6604 Remote Similarity NPC293183
0.6481 Remote Similarity NPC306821
0.6182 Remote Similarity NPC488084
0.6182 Remote Similarity NPC239128
0.5893 Remote Similarity NPC301323
0.5893 Remote Similarity NPC275722
0.5893 Remote Similarity NPC127447
0.5893 Remote Similarity NPC187498
0.5893 Remote Similarity NPC600177
0.5789 Remote Similarity NPC53181
0.5789 Remote Similarity NPC18260
0.5789 Remote Similarity NPC176775
0.5789 Remote Similarity NPC231018
0.5614 Remote Similarity NPC191459
0.5614 Remote Similarity NPC194281
0.5517 Remote Similarity NPC130894
0.5517 Remote Similarity NPC188203
0.5439 Remote Similarity NPC7973
0.5439 Remote Similarity NPC250822
0.5424 Remote Similarity NPC222830
0.5424 Remote Similarity NPC201136
0.5357 Remote Similarity NPC602026
0.5345 Remote Similarity NPC71334
0.5345 Remote Similarity NPC241498
0.5345 Remote Similarity NPC156222
0.5345 Remote Similarity NPC609062
0.5333 Remote Similarity NPC204854
0.5333 Remote Similarity NPC183878
0.5273 Remote Similarity NPC41721
0.5254 Remote Similarity NPC604462
0.5246 Remote Similarity NPC78302
0.5246 Remote Similarity NPC288669
0.5246 Remote Similarity NPC196439
0.5246 Remote Similarity NPC2476
0.5246 Remote Similarity NPC608539
0.5172 Remote Similarity NPC245546
0.5172 Remote Similarity NPC607196
0.5167 Remote Similarity NPC217186
0.5161 Remote Similarity NPC227325
0.5091 Remote Similarity NPC197425
0.5088 Remote Similarity NPC278556
0.5085 Remote Similarity NPC284552

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC602963 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