Natural Product: NPC536509

Natural Product IDNPC536509
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Laciniatin
IUPAC Name 3,5,7-trihydroxy-2-(3-hydroxy-4-methoxy-phenyl)-6-methoxy-chromen-4-one
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 MBAMSENKVRMPKA-UHFFFAOYSA-N
Standard InCHI InChI=1S/C17H14O8/c1-23-10-4-3-7(5-8(10)18)16-15(22)13(20)12-11(25-16)6-9(19)17(24-2)14(12)21/h3-6,18-19,21-22H,1-2H3
SMILES COC1=CC=C(C2=C(O)C(=O)C3=C(O)C(OC)=C(O)C=C3O2)C=C1O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   346.07 Volume:   326.149
?
Van der Waals volume.
Dense:   1.061 LogP:   1.643
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.788
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.696
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   18.0
TPSA:   129.59
?
Topological Polar Surface Area.
 H-Bond Acceptor:   8.0
H-Bond Donor:   4.0 Rings:   3.0
Heavy Atoms:   8.0

MedChem Properties

QED Drug-Likeness Score:   0.568 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.601 Fsp3:   0.118
MCE-18:   20.0
?
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:   0.813 Fluc inhibitor:   0.638
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.904
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.578
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.478 Promiscuous compounds:   0.898

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.389 MDCK Permeability:   -4.83
Pgp-inhibitor:   0.694 Pgp-substrate:   0.124
PAMPA:   0.167
?
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):   0.172
20% Bioavailability (F20%):   0.086 30% Bioavailability (F30%):   0.834
50% Bioavailability (F50%):   0.995

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.001 MRP1:   0.814
Plasma Protein Binding (PPB):   97.659% Volume Distribution (VD):   -0.704
Fu: 2.923%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.976
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   0.991
BSEP inhibitor:   0.271

ADMET: Metabolism

CYP1A2-inhibitor:   0.976 CYP1A2-substrate:   0.552
CYP2C19-inhibitor:   0.003 CYP2C19-substrate:   0.83
CYP2C9-inhibitor:   0.959 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.988 CYP2D6-substrate:   0.464
CYP3A4-inhibitor:   0.003 CYP3A4-substrate:   0.007
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.995
HLM stability:   0.998
?
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):  2.856 Half-life (T1/2):  1.68

ADMET: Toxicity

hERG Blockers:  0.068 hERG Blockers (10um):  0.468
Human Hepatotoxicity (H-HT):  0.412 Drug-induced Liver Injury (DILI):  0.703
AMES Toxicity:  0.51 Rat Oral Acute Toxicity:  0.425
Maximum Recommended Daily Dose:  0.521 Skin Sensitization:  0.719
Carcinogencity:  0.659 Eye Corrosion:  0.462
Eye Irritation:  0.991 Respiratory Toxicity:  0.728
Drug-induced Neurotoxicity:  0.073 Ototoxicity:  0.164
Hematotoxicity:  0.17 Drug-induced Nephrotoxicity:  0.091
Genotoxicity:  0.499 RPMI-8226 Immunitoxicity:  0.085
A549 Cytotoxicity:  0.29 Hek293 Cytotoxicity:  0.368
BCF:   0.788
?
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:   3.496
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.419
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.908
?
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
NPO15117 Chromolaena odorata Species Asteraceae Eukaryota n.a. n.a. n.a. DOI[10.1016/S0031-9422(00)88710-5]
NPO9829 Arnica chamissonis Species Asteraceae Eukaryota n.a. rhizome n.a. PMID[16644542]
NPO12107 Arnica montana Species Asteraceae Eukaryota n.a. rhizome n.a. PMID[16644542]
NPO9829 Arnica chamissonis Species Asteraceae Eukaryota n.a. root n.a. PMID[16644542]
NPO12107 Arnica montana Species Asteraceae Eukaryota n.a. root n.a. PMID[16644542]
NPO15117 Chromolaena odorata Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[23186307]
NPO9829 Arnica chamissonis Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[23501116]
NPO12107 Arnica montana Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[23501116]
NPO15134 Alnus glutinosa Species Betulaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO63037 Brickellia laciniata Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12107 Arnica montana Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9829 Arnica chamissonis Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15117 Chromolaena odorata Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15134 Alnus glutinosa Species Betulaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO15134 Alnus glutinosa Species Betulaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO12107 Arnica montana Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO15117 Chromolaena odorata Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO12107 Arnica montana Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO12107 Arnica montana Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9829 Arnica chamissonis Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15117 Chromolaena odorata Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15134 Alnus glutinosa Species Betulaceae 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 NPC536509 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
0.82 Intermediate Similarity NPC44079
0.7843 Intermediate Similarity NPC98661
0.7647 Intermediate Similarity NPC26227
0.7593 Intermediate Similarity NPC93376
0.7407 Intermediate Similarity NPC54394
0.7222 Intermediate Similarity NPC9609
0.7222 Intermediate Similarity NPC256283
0.7091 Intermediate Similarity NPC200740
0.6667 Remote Similarity NPC189179
0.6667 Remote Similarity NPC75215
0.6491 Remote Similarity NPC55205
0.629 Remote Similarity NPC130955
0.614 Remote Similarity NPC50403
0.6034 Remote Similarity NPC49824
0.5965 Remote Similarity NPC203891
0.5965 Remote Similarity NPC156222
0.5932 Remote Similarity NPC115798
0.5932 Remote Similarity NPC255350
0.5862 Remote Similarity NPC241838
0.5738 Remote Similarity NPC482982
0.5667 Remote Similarity NPC82325
0.5667 Remote Similarity NPC209487
0.5667 Remote Similarity NPC159103
0.5667 Remote Similarity NPC29841
0.5645 Remote Similarity NPC227192
0.5593 Remote Similarity NPC100887
0.5593 Remote Similarity NPC163524
0.5574 Remote Similarity NPC52005
0.5574 Remote Similarity NPC609179
0.5517 Remote Similarity NPC472438
0.5517 Remote Similarity NPC293183
0.5484 Remote Similarity NPC125062
0.5424 Remote Similarity NPC241498
0.5424 Remote Similarity NPC284552
0.5424 Remote Similarity NPC219330
0.5424 Remote Similarity NPC266960
0.541 Remote Similarity NPC204854
0.541 Remote Similarity NPC270620
0.541 Remote Similarity NPC146165
0.541 Remote Similarity NPC83508
0.541 Remote Similarity NPC166753
0.5373 Remote Similarity NPC213622
0.5333 Remote Similarity NPC201451
0.5333 Remote Similarity NPC87125
0.5333 Remote Similarity NPC28274
0.5323 Remote Similarity NPC25495
0.5323 Remote Similarity NPC160951
0.5323 Remote Similarity NPC223579
0.5238 Remote Similarity NPC252933
0.5238 Remote Similarity NPC133953
0.5224 Remote Similarity NPC470402
0.5167 Remote Similarity NPC152042
0.5161 Remote Similarity NPC300943
0.5161 Remote Similarity NPC212678
0.5082 Remote Similarity NPC276905
0.5082 Remote Similarity NPC143799
0.5082 Remote Similarity NPC281207
0.5082 Remote Similarity NPC605146
0.5082 Remote Similarity NPC605755
0.5079 Remote Similarity NPC224137
0.5079 Remote Similarity NPC287101
0.5079 Remote Similarity NPC474520
0.5079 Remote Similarity NPC4481
0.5079 Remote Similarity NPC196439
0.5079 Remote Similarity NPC607642
0.5079 Remote Similarity NPC608258
0.5068 Remote Similarity NPC254306

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC536509 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
0.5932 Remote Similarity NPD2801 Pre-clinical

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