Natural Product: NPC88964

Natural Product IDNPC88964
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Sanggenon H
IUPAC Name (2S)-5,7-dihydroxy-2-(5-hydroxy-2,2-dimethylchromen-8-yl)-2,3-dihydrochromen-4-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL3288838
PubChem CID 90681446
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0000337] Flavans
          • [CHEMONTID:0001632] Flavanones

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 QPAKXSCQEJXHSW-INIZCTEOSA-N
Standard InCHI InChI=1S/C20H18O6/c1-20(2)6-5-11-13(22)4-3-12(19(11)26-20)16-9-15(24)18-14(23)7-10(21)8-17(18)25-16/h3-8,16,21-23H,9H2,1-2H3/t16-/m0/s1
SMILES CC1(C)C=Cc2c(ccc([C@@H]3CC(=O)c4c(cc(cc4O3)O)O)c2O1)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   354.11 Volume:   351.9
?
Van der Waals volume.
Dense:   1.006 LogP:   3.512
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.252
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.343
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   23.0
TPSA:   96.22
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   3.0 Rings:   4.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.723 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.593 Fsp3:   0.25
MCE-18:   81.0
?
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:   0 PAINS Alert:   0
Colloidal aggregators:   0.678 Fluc inhibitor:   0.873
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.625
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.532
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.355 Promiscuous compounds:   0.186

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.016 MDCK Permeability:   -4.773
Pgp-inhibitor:   0.381 Pgp-substrate:   0.069
PAMPA:   0.15
?
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%):   0.53 30% Bioavailability (F30%):   0.994
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.046 MRP1:   0.905
Plasma Protein Binding (PPB):   95.93% Volume Distribution (VD):   0.262
Fu: 4.244%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   0.995 BCRP inhibitor:   0.981
BSEP inhibitor:   0.97

ADMET: Metabolism

CYP1A2-inhibitor:   0.379 CYP1A2-substrate:   0.995
CYP2C19-inhibitor:   0.002 CYP2C19-substrate:   0.961
CYP2C9-inhibitor:   0.513 CYP2C9-substrate:   0.055
CYP2D6-inhibitor:   0.043 CYP2D6-substrate:   0.992
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.98
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
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):  4.824 Half-life (T1/2):  1.48

ADMET: Toxicity

hERG Blockers:  0.106 hERG Blockers (10um):  0.512
Human Hepatotoxicity (H-HT):  0.72 Drug-induced Liver Injury (DILI):  0.767
AMES Toxicity:  0.866 Rat Oral Acute Toxicity:  0.82
Maximum Recommended Daily Dose:  0.863 Skin Sensitization:  0.888
Carcinogencity:  0.765 Eye Corrosion:  0.005
Eye Irritation:  0.962 Respiratory Toxicity:  0.97
Drug-induced Neurotoxicity:  0.577 Ototoxicity:  0.389
Hematotoxicity:  0.123 Drug-induced Nephrotoxicity:  0.597
Genotoxicity:  0.988 RPMI-8226 Immunitoxicity:  0.199
A549 Cytotoxicity:  0.787 Hek293 Cytotoxicity:  0.817
BCF:   1.658
?
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:   4.326
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.751
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.002
?
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
NPO28265 Morus alba Species Moraceae Eukaryota n.a. n.a. n.a. PMID[20815207]
NPO28265 Morus alba Species Moraceae Eukaryota n.a. bark n.a. PMID[21319773]
NPO28265 Morus alba Species Moraceae Eukaryota n.a. leaf n.a. PMID[21319773]
NPO28265 Morus alba Species Moraceae Eukaryota n.a. root n.a. PMID[21319773]
NPO28265 Morus alba Species Moraceae Eukaryota n.a. leaf n.a. PMID[22207282]
NPO28265 Morus alba Species Moraceae Eukaryota n.a. root n.a. PMID[23806866]
NPO28265 Morus alba Species Moraceae Eukaryota root bark University of Veterinary and Pharmaceutical Sciences Brno (UVPS Brno), Brno, Czech Republic 2011-APR PMID[24901948]
NPO28265 Morus alba Species Moraceae Eukaryota n.a. Konya, Turkey 2007-APR PMID[24901948]
NPO28265 Morus alba Species Moraceae Eukaryota leaves Chungbuk, Korea n.a. PMID[25935644]
NPO28265 Morus alba Species Moraceae Eukaryota n.a. root n.a. PMID[25981820]
NPO28265 Morus alba Species Moraceae Eukaryota n.a. latex n.a. PMID[27294120]
NPO28265 Morus alba Species Moraceae Eukaryota Root barks n.a. n.a. PMID[3097265]
NPO28265 Morus alba Species Moraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28265 Morus alba Species Moraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO28265 Morus alba Species Moraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO28265 Morus alba Species Moraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO28265 Morus alba Species Moraceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO28265 Morus alba Species Moraceae 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
NPT1970 Cell line THP-1 Homo sapiens IC50 > 10000.0 nM PMID[24901948]

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 NPC88964 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
0.6377 Remote Similarity NPC312973
0.6216 Remote Similarity NPC111786
0.6197 Remote Similarity NPC272502
0.5972 Remote Similarity NPC118256
0.5921 Remote Similarity NPC186686
0.589 Remote Similarity NPC473272
0.5833 Remote Similarity NPC301276
0.5806 Remote Similarity NPC32441
0.5806 Remote Similarity NPC79943
0.5797 Remote Similarity NPC109223
0.5797 Remote Similarity NPC10937
0.5781 Remote Similarity NPC321011
0.5781 Remote Similarity NPC294852
0.5781 Remote Similarity NPC188679
0.5775 Remote Similarity NPC470647
0.5694 Remote Similarity NPC78247
0.5641 Remote Similarity NPC43319
0.5556 Remote Similarity NPC295261
0.5556 Remote Similarity NPC296490
0.5441 Remote Similarity NPC236637
0.5385 Remote Similarity NPC107586
0.5312 Remote Similarity NPC243083
0.5312 Remote Similarity NPC13768
0.5312 Remote Similarity NPC287246
0.5312 Remote Similarity NPC12296
0.5256 Remote Similarity NPC195621
0.5205 Remote Similarity NPC20488
0.52 Remote Similarity NPC611447
0.5156 Remote Similarity NPC182421
0.5152 Remote Similarity NPC274784
0.5152 Remote Similarity NPC20709
0.5143 Remote Similarity NPC258630
0.5139 Remote Similarity NPC17170
0.5128 Remote Similarity NPC214774
0.5128 Remote Similarity NPC474038
0.5065 Remote Similarity NPC474021
0.5063 Remote Similarity NPC475784

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC88964 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
0.5806 Remote Similarity NPD1552 Clinical (unspecified phase)
0.5312 Remote Similarity NPD1550 Phase 2

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