Natural Product: NPC516576

Natural Product IDNPC516576
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Haplogenin
IUPAC Name 3,5,7,8-tetrahydroxy-2-(4-hydroxy-3-methoxy-phenyl)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 QBFAWRDCFGNKSP-UHFFFAOYSA-N
Standard InCHI InChI=1S/C16H12O8/c1-23-10-4-6(2-3-7(10)17)15-14(22)13(21)11-8(18)5-9(19)12(20)16(11)24-15/h2-5,17-20,22H,1H3
SMILES COC1=CC(C2=C(O)C(=O)C3=C(O)C=C(O)C(O)=C3O2)=CC=C1O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   332.05 Volume:   308.853
?
Van der Waals volume.
Dense:   1.075 LogP:   1.489
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.592
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.86
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   18.0
TPSA:   140.59
?
Topological Polar Surface Area.
 H-Bond Acceptor:   8.0
H-Bond Donor:   5.0 Rings:   3.0
Heavy Atoms:   8.0

MedChem Properties

QED Drug-Likeness Score:   0.354 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.631 Fsp3:   0.062
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:   1
Chelating Alert:   1 PAINS Alert:   1
Colloidal aggregators:   0.84 Fluc inhibitor:   0.335
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.816
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.324
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.566 Promiscuous compounds:   0.906

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.713 MDCK Permeability:   -4.876
Pgp-inhibitor:   0.271 Pgp-substrate:   0.016
PAMPA:   0.394
?
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):   0.171
20% Bioavailability (F20%):   0.269 30% Bioavailability (F30%):   0.932
50% Bioavailability (F50%):   0.997

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.904
Plasma Protein Binding (PPB):   98.451% Volume Distribution (VD):   -0.815
Fu: 1.395%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.995
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.996
BSEP inhibitor:   0.514

ADMET: Metabolism

CYP1A2-inhibitor:   0.425 CYP1A2-substrate:   0.018
CYP2C19-inhibitor:   0.002 CYP2C19-substrate:   0.294
CYP2C9-inhibitor:   0.296 CYP2C9-substrate:   0.003
CYP2D6-inhibitor:   0.834 CYP2D6-substrate:   0.724
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.88
HLM stability:   0.866
?
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):  6.026 Half-life (T1/2):  2.033

ADMET: Toxicity

hERG Blockers:  0.035 hERG Blockers (10um):  0.427
Human Hepatotoxicity (H-HT):  0.393 Drug-induced Liver Injury (DILI):  0.82
AMES Toxicity:  0.648 Rat Oral Acute Toxicity:  0.47
Maximum Recommended Daily Dose:  0.544 Skin Sensitization:  0.828
Carcinogencity:  0.51 Eye Corrosion:  0.129
Eye Irritation:  0.99 Respiratory Toxicity:  0.717
Drug-induced Neurotoxicity:  0.008 Ototoxicity:  0.18
Hematotoxicity:  0.092 Drug-induced Nephrotoxicity:  0.045
Genotoxicity:  0.832 RPMI-8226 Immunitoxicity:  0.055
A549 Cytotoxicity:  0.561 Hek293 Cytotoxicity:  0.363
BCF:   0.897
?
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:   3.538
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.309
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.765
?
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
NPO49671 Coronilla valentina Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1002 Haplophyllum perforatum Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO96 Rhododendron capitatum Species Ericaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1002 Haplophyllum perforatum Species Rutaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO96 Rhododendron capitatum Species Ericaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO1002 Haplophyllum perforatum Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO96 Rhododendron capitatum Species Ericaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO96 Rhododendron capitatum Species Ericaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO96 Rhododendron capitatum Species Ericaceae 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 NPC516576 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
0.7241 Intermediate Similarity NPC610401
0.717 Intermediate Similarity NPC27208
0.7119 Intermediate Similarity NPC125062
0.7037 Intermediate Similarity NPC225731
0.6557 Remote Similarity NPC252933
0.6333 Remote Similarity NPC32420
0.619 Remote Similarity NPC227192
0.5873 Remote Similarity NPC602125
0.5806 Remote Similarity NPC480465
0.5781 Remote Similarity NPC279989
0.5781 Remote Similarity NPC604021
0.5738 Remote Similarity NPC287979
0.5538 Remote Similarity NPC183950
0.5538 Remote Similarity NPC133953
0.5484 Remote Similarity NPC98661
0.5469 Remote Similarity NPC54394
0.5469 Remote Similarity NPC253634
0.5397 Remote Similarity NPC87125
0.5397 Remote Similarity NPC28274
0.5303 Remote Similarity NPC78326
0.5246 Remote Similarity NPC179271
0.5231 Remote Similarity NPC159103
0.5156 Remote Similarity NPC50403
0.5156 Remote Similarity NPC201451
0.5156 Remote Similarity NPC143799
0.5152 Remote Similarity NPC609179
0.5082 Remote Similarity NPC296197
0.5082 Remote Similarity NPC20791
0.5075 Remote Similarity NPC137062

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC516576 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
0.5082 Remote Similarity NPD1512 Phase 3

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