Natural Product: NPC544608

Natural Product IDNPC544608
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Scutellarin methylester
IUPAC Name methyl (2~{S},3~{S},4~{S},5~{R},6~{S})-6-[5,6-dihydroxy-2-(4-hydroxyphenyl)-4-oxo-chromen-7-yl]oxy-3,4,5-trihydroxy-tetrahydropyran-2-carboxylate
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
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 LNIVUWPCHRNJLG-SXFAUFNYSA-N
Standard InCHI InChI=1S/C22H20O12/c1-31-21(30)20-18(28)17(27)19(29)22(34-20)33-13-7-12-14(16(26)15(13)25)10(24)6-11(32-12)8-2-4-9(23)5-3-8/h2-7,17-20,22-23,25-29H,1H3/t17-,18-,19+,20-,22+/m0/s1
SMILES COC(=O)[C@H]1O[C@@H](OC2=CC3=C(C(O)=C2O)C(=O)C=C(C2=CC=C(O)C=C2)O3)[C@H](O)[C@@H](O)[C@@H]1O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   476.1 Volume:   436.597
?
Van der Waals volume.
Dense:   1.09 LogP:   0.851
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.265
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.51
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   25.0
TPSA:   196.35
?
Topological Polar Surface Area.
 H-Bond Acceptor:   12.0
H-Bond Donor:   6.0 Rings:   4.0
Heavy Atoms:   12.0

MedChem Properties

QED Drug-Likeness Score:   0.217 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.034 Fsp3:   0.273
MCE-18:   90.643
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Accepted
Pfizer Rule:   Rejected GSK Rule:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   1 PAINS Alert:   1
Colloidal aggregators:   0.571 Fluc inhibitor:   0.333
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.949
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.887
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.127 Promiscuous compounds:   0.536

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.394 MDCK Permeability:   -5.311
Pgp-inhibitor:   0.0 Pgp-substrate:   0.461
PAMPA:   0.995
?
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):   0.052
20% Bioavailability (F20%):   0.599 30% Bioavailability (F30%):   0.962
50% Bioavailability (F50%):   0.997

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.514
Plasma Protein Binding (PPB):   84.887% Volume Distribution (VD):   0.022
Fu: 13.302%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.935
OATP1B3 inhibitor:   0.969 BCRP inhibitor:   0.707
BSEP inhibitor:   0.184

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.002 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.001 CYP2D6-substrate:   0.013
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.366
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.741
HLM stability:   0.002
?
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):  2.849 Half-life (T1/2):  3.548

ADMET: Toxicity

hERG Blockers:  0.03 hERG Blockers (10um):  0.269
Human Hepatotoxicity (H-HT):  0.404 Drug-induced Liver Injury (DILI):  0.939
AMES Toxicity:  0.672 Rat Oral Acute Toxicity:  0.111
Maximum Recommended Daily Dose:  0.271 Skin Sensitization:  0.953
Carcinogencity:  0.104 Eye Corrosion:  0.0
Eye Irritation:  0.885 Respiratory Toxicity:  0.068
Drug-induced Neurotoxicity:  0.01 Ototoxicity:  0.319
Hematotoxicity:  0.107 Drug-induced Nephrotoxicity:  0.391
Genotoxicity:  0.938 RPMI-8226 Immunitoxicity:  0.116
A549 Cytotoxicity:  0.245 Hek293 Cytotoxicity:  0.492
BCF:   0.556
?
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:   3.217
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.581
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.978
?
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
NPO15289 Scoparia dulcis Species Plantaginaceae Eukaryota n.a. n.a. n.a. PMID[12880314]
NPO15289 Scoparia dulcis Species Plantaginaceae Eukaryota n.a. whole plant n.a. PMID[1294695]
NPO15289 Scoparia dulcis Species Plantaginaceae Eukaryota n.a. n.a. n.a. PMID[15104516]
NPO15289 Scoparia dulcis Species Plantaginaceae Eukaryota leaves and twigs Taiwan n.a. PMID[1659612]
NPO15289 Scoparia dulcis Species Plantaginaceae Eukaryota aerial parts Nanning, Guangxi Zhuang Autonomous Region, Peoples Republic of China 2012-OCT PMID[24955889]
NPO15289 Scoparia dulcis Species Plantaginaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15289 Scoparia dulcis Species Plantaginaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO15289 Scoparia dulcis Species Plantaginaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO15289 Scoparia dulcis Species Plantaginaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO15289 Scoparia dulcis Species Plantaginaceae 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 NPC544608 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
0.7973 Intermediate Similarity NPC146792
0.7763 Intermediate Similarity NPC27942
0.6962 Remote Similarity NPC58716
0.6923 Remote Similarity NPC45618
0.6875 Remote Similarity NPC198324
0.675 Remote Similarity NPC181712
0.6667 Remote Similarity NPC4390
0.6506 Remote Similarity NPC43211
0.6286 Remote Similarity NPC198826
0.622 Remote Similarity NPC93337
0.6173 Remote Similarity NPC331652
0.6145 Remote Similarity NPC84265
0.6145 Remote Similarity NPC105025
0.6098 Remote Similarity NPC39360
0.6098 Remote Similarity NPC29763
0.6098 Remote Similarity NPC210003
0.6092 Remote Similarity NPC172807
0.6092 Remote Similarity NPC477848
0.5977 Remote Similarity NPC190003
0.5952 Remote Similarity NPC472385
0.5824 Remote Similarity NPC3583
0.5632 Remote Similarity NPC237435
0.5581 Remote Similarity NPC245014
0.5581 Remote Similarity NPC610763
0.5543 Remote Similarity NPC44931
0.5532 Remote Similarity NPC64051
0.5529 Remote Similarity NPC58053
0.5521 Remote Similarity NPC270675
0.5521 Remote Similarity NPC195685
0.5465 Remote Similarity NPC95090
0.5465 Remote Similarity NPC27408
0.5455 Remote Similarity NPC175107
0.5446 Remote Similarity NPC472993
0.5408 Remote Similarity NPC298171
0.5405 Remote Similarity NPC57030
0.5402 Remote Similarity NPC186807
0.5402 Remote Similarity NPC45638
0.54 Remote Similarity NPC599948
0.5393 Remote Similarity NPC601144
0.5393 Remote Similarity NPC605067
0.5354 Remote Similarity NPC472994
0.5349 Remote Similarity NPC19709
0.5349 Remote Similarity NPC83283
0.5341 Remote Similarity NPC201292
0.5333 Remote Similarity NPC311830
0.5333 Remote Similarity NPC162313
0.5333 Remote Similarity NPC602805
0.5326 Remote Similarity NPC254540
0.5287 Remote Similarity NPC259152
0.5287 Remote Similarity NPC189142
0.5287 Remote Similarity NPC77660
0.5275 Remote Similarity NPC469931
0.527 Remote Similarity NPC275722
0.5253 Remote Similarity NPC101636
0.5222 Remote Similarity NPC22832
0.5222 Remote Similarity NPC115760
0.5222 Remote Similarity NPC243930
0.5222 Remote Similarity NPC601710
0.5217 Remote Similarity NPC211594
0.5195 Remote Similarity NPC283600
0.5172 Remote Similarity NPC261866
0.5172 Remote Similarity NPC143851
0.5158 Remote Similarity NPC473512
0.5158 Remote Similarity NPC129827
0.5111 Remote Similarity NPC191306
0.5111 Remote Similarity NPC609451
0.5065 Remote Similarity NPC212678

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC544608 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
0.5632 Remote Similarity NPD4338 Clinical (unspecified phase)

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