Natural Product: NPC225778

Natural Product IDNPC225778
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 MGJLSBDCWOSMHL-VOFPXKNKSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 5320293
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0002506] Isoflavonoids
        • [CHEMONTID:0000507] Isoflavonoid O-glycosides

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 MGJLSBDCWOSMHL-VOFPXKNKSA-N
Standard InCHI InChI=1S/C22H22O9/c1-28-12-4-2-11(3-5-12)15-10-29-16-8-13(6-7-14(16)18(15)24)30-22-21(27)20(26)19(25)17(9-23)31-22/h2-8,10,17,19-23,25-27H,9H2,1H3/t17-,19-,20+,21-,22+/m1/s1
SMILES COc1ccc(cc1)c1coc2cc(ccc2c1=O)O[C@@H]1[C@@H]([C@H]([C@@H]([C@@H](CO)O1)O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   430.13 Volume:   412.863
?
Van der Waals volume.
Dense:   1.042 LogP:   0.925
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.577
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.115
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   24.0
TPSA:   138.82
?
Topological Polar Surface Area.
 H-Bond Acceptor:   9.0
H-Bond Donor:   4.0 Rings:   4.0
Heavy Atoms:   9.0

MedChem Properties

QED Drug-Likeness Score:   0.459 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.588 Fsp3:   0.318
MCE-18:   80.276
?
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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.556 Fluc inhibitor:   0.9
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.917
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.547
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.151 Promiscuous compounds:   0.07

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.008 MDCK Permeability:   -5.11
Pgp-inhibitor:   0.004 Pgp-substrate:   0.108
PAMPA:   0.97
?
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):   0.775
20% Bioavailability (F20%):   0.113 30% Bioavailability (F30%):   0.795
50% Bioavailability (F50%):   0.86

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.002 MRP1:   0.106
Plasma Protein Binding (PPB):   81.944% Volume Distribution (VD):   -0.033
Fu: 19.516%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.998
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.22
BSEP inhibitor:   0.315

ADMET: Metabolism

CYP1A2-inhibitor:   0.846 CYP1A2-substrate:   0.134
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.146
CYP2C9-inhibitor:   0.943 CYP2C9-substrate:   0.015
CYP2D6-inhibitor:   0.958 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.699
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
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):  2.75 Half-life (T1/2):  3.252

ADMET: Toxicity

hERG Blockers:  0.114 hERG Blockers (10um):  0.265
Human Hepatotoxicity (H-HT):  0.558 Drug-induced Liver Injury (DILI):  0.956
AMES Toxicity:  0.852 Rat Oral Acute Toxicity:  0.063
Maximum Recommended Daily Dose:  0.131 Skin Sensitization:  0.717
Carcinogencity:  0.379 Eye Corrosion:  0.0
Eye Irritation:  0.234 Respiratory Toxicity:  0.076
Drug-induced Neurotoxicity:  0.115 Ototoxicity:  0.941
Hematotoxicity:  0.274 Drug-induced Nephrotoxicity:  0.843
Genotoxicity:  0.331 RPMI-8226 Immunitoxicity:  0.121
A549 Cytotoxicity:  0.186 Hek293 Cytotoxicity:  0.221
BCF:   0.657
?
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:   3.385
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.705
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.125
?
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
NPO7154 Glycyrrhiza uralensis Species Fabaceae Eukaryota n.a. n.a. n.a. DOI[10.1007/s11164-015-2099-x]
NPO24846 Astragalus membranaceus Species Fabaceae Eukaryota n.a. root n.a. DOI[10.1021/np50075a009]
NPO7154 Glycyrrhiza uralensis Species Fabaceae Eukaryota n.a. n.a. n.a. DOI[10.1134/S1021443711030101]
NPO15715 Astragalus mongholicus Species Fabaceae Eukaryota n.a. root n.a. PMID[15763368]
NPO7154 Glycyrrhiza uralensis Species Fabaceae Eukaryota n.a. root n.a. PMID[16441081]
NPO15462 Angelica sinensis Species Apiaceae Eukaryota roots purchased from Kiu Shun Trading Ltd., Vancouver, Canada 2000 PMID[16643021]
NPO7154 Glycyrrhiza uralensis Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[16675659]
NPO24846 Astragalus membranaceus Species Fabaceae Eukaryota n.a. root n.a. PMID[17253088]
NPO7154 Glycyrrhiza uralensis Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[22074222]
NPO7154 Glycyrrhiza uralensis Species Fabaceae Eukaryota n.a. root n.a. PMID[22074222]
NPO7154 Glycyrrhiza uralensis Species Fabaceae Eukaryota n.a. root n.a. PMID[23867078]
NPO7154 Glycyrrhiza uralensis Species Fabaceae Eukaryota n.a. rhizome n.a. PMID[23867078]
NPO7154 Glycyrrhiza uralensis Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[24479468]
NPO7154 Glycyrrhiza uralensis Species Fabaceae Eukaryota roots n.a. n.a. PMID[24957203]
NPO24846 Astragalus membranaceus Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[25068786]
NPO7154 Glycyrrhiza uralensis Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[25445757]
NPO15462 Angelica sinensis Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[25538068]
NPO7154 Glycyrrhiza uralensis Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[25744461]
NPO15715 Astragalus mongholicus Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[25844502]
NPO7154 Glycyrrhiza uralensis Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[26841168]
NPO15462 Angelica sinensis Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[27400088]
NPO24846 Astragalus membranaceus Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[30758201]
NPO7154 Glycyrrhiza uralensis Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[32196343]
NPO15462 Angelica sinensis Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[36838931]
NPO15462 Angelica sinensis Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[37480748]
NPO15715 Astragalus mongholicus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20554 Astragalus complanatus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24846 Astragalus membranaceus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7154 Glycyrrhiza uralensis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15462 Angelica sinensis Species Apiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15462 Angelica sinensis Species Apiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO20554 Astragalus complanatus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO24846 Astragalus membranaceus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO7154 Glycyrrhiza uralensis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO15715 Astragalus mongholicus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO15715 Astragalus mongholicus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[MetaboLights]
NPO7154 Glycyrrhiza uralensis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO20554 Astragalus complanatus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO15462 Angelica sinensis Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO24846 Astragalus membranaceus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO15715 Astragalus mongholicus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO24846 Astragalus membranaceus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO20554 Astragalus complanatus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO15715 Astragalus mongholicus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO15462 Angelica sinensis Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO7154 Glycyrrhiza uralensis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO20554 Astragalus complanatus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO15715 Astragalus mongholicus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO7154 Glycyrrhiza uralensis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO24846 Astragalus membranaceus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO15462 Angelica sinensis Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO15715 Astragalus mongholicus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20554 Astragalus complanatus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24846 Astragalus membranaceus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15462 Angelica sinensis Species Apiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7154 Glycyrrhiza uralensis Species Fabaceae 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 NPC225778 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
1.0 High Similarity NPC45165
0.8333 Intermediate Similarity NPC229729
0.8286 Intermediate Similarity NPC161749
0.8261 Intermediate Similarity NPC135345
0.7838 Intermediate Similarity NPC601607
0.7826 Intermediate Similarity NPC25547
0.7534 Intermediate Similarity NPC603782
0.7297 Intermediate Similarity NPC258035
0.72 Intermediate Similarity NPC73511
0.6933 Remote Similarity NPC211014
0.6842 Remote Similarity NPC105511
0.6456 Remote Similarity NPC100720
0.6447 Remote Similarity NPC487214
0.641 Remote Similarity NPC156457
0.6406 Remote Similarity NPC182428
0.6296 Remote Similarity NPC43761
0.625 Remote Similarity NPC205076
0.622 Remote Similarity NPC307518
0.6203 Remote Similarity NPC197896
0.6203 Remote Similarity NPC313163
0.6173 Remote Similarity NPC479402
0.6067 Remote Similarity NPC51326
0.6044 Remote Similarity NPC235575
0.6 Remote Similarity NPC234739
0.5952 Remote Similarity NPC479407
0.5942 Remote Similarity NPC136095
0.5783 Remote Similarity NPC224462
0.5783 Remote Similarity NPC479401
0.5765 Remote Similarity NPC48773
0.5761 Remote Similarity NPC231194
0.575 Remote Similarity NPC160515
0.5679 Remote Similarity NPC259070
0.5647 Remote Similarity NPC479406
0.5616 Remote Similarity NPC103409
0.561 Remote Similarity NPC168822
0.561 Remote Similarity NPC95090
0.561 Remote Similarity NPC27408
0.5542 Remote Similarity NPC186807
0.5541 Remote Similarity NPC254741
0.5493 Remote Similarity NPC181124
0.5488 Remote Similarity NPC58053
0.5488 Remote Similarity NPC478528
0.5476 Remote Similarity NPC138540
0.5465 Remote Similarity NPC607201
0.5441 Remote Similarity NPC120924
0.5429 Remote Similarity NPC185607
0.5412 Remote Similarity NPC481043
0.5412 Remote Similarity NPC80140
0.5281 Remote Similarity NPC487212
0.5275 Remote Similarity NPC479405
0.5275 Remote Similarity NPC475155
0.5217 Remote Similarity NPC479404
0.5139 Remote Similarity NPC479067
0.5139 Remote Similarity NPC603503
0.5119 Remote Similarity NPC348541
0.5116 Remote Similarity NPC182045
0.5068 Remote Similarity NPC186507
0.5068 Remote Similarity NPC209560
0.5068 Remote Similarity NPC490700
0.5067 Remote Similarity NPC602183

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC225778 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
0.8286 Intermediate Similarity NPD4381 Clinical (unspecified phase)
0.5366 Remote Similarity NPD3818 Discontinued
0.5139 Remote Similarity NPD2796 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