Natural Product: NPC65665

Natural Product IDNPC65665
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Morroniside
IUPAC Name methyl (1S,3R,4aS,8S,8aS)-3-hydroxy-1-methyl-8-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-1,3,4,4a,8,8a-hexahydropyrano[3,4-c]pyran-5-carboxylate
Synonyms (7Beta-Hydroxy)-Morroniside; Morroniside
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1209803
PubChem CID 11228693
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0004603] Organic oxygen compounds
      • [CHEMONTID:0000323] Organooxygen compounds
        • [CHEMONTID:0000011] Carbohydrates and carbohydrate conjugates
          • [CHEMONTID:0002105] Glycosyl compounds
            • [CHEMONTID:0002207] O-glycosyl 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 YTZSBJLNMIQROD-SFBCHFHNSA-N
Standard InCHI InChI=1S/C17H26O11/c1-6-11-7(3-10(19)26-6)8(15(23)24-2)5-25-16(11)28-17-14(22)13(21)12(20)9(4-18)27-17/h5-7,9-14,16-22H,3-4H2,1-2H3/t6-,7+,9+,10+,11+,12+,13-,14+,16-,17-/m0/s1
SMILES C[C@H]1[C@@H]2[C@H](C[C@H](O)O1)C(=CO[C@H]2O[C@H]1[C@@H]([C@H]([C@@H]([C@@H](CO)O1)O)O)O)C(=O)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   406.15 Volume:   368.338
?
Van der Waals volume.
Dense:   1.103 LogP:   -0.899
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   -0.425
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -0.703
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   18.0
TPSA:   164.37
?
Topological Polar Surface Area.
 H-Bond Acceptor:   11.0
H-Bond Donor:   5.0 Rings:   3.0
Heavy Atoms:   11.0

MedChem Properties

QED Drug-Likeness Score:   0.315 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.841 Fsp3:   0.824
MCE-18:   56.903
?
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:   0.405 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.085
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.001
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.284 Promiscuous compounds:   0.067

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.814 MDCK Permeability:   -5.229
Pgp-inhibitor:   0.0 Pgp-substrate:   0.642
PAMPA:   0.975
?
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):   0.503
20% Bioavailability (F20%):   0.248 30% Bioavailability (F30%):   0.96
50% Bioavailability (F50%):   0.926

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.039 MRP1:   0.821
Plasma Protein Binding (PPB):   38.743% Volume Distribution (VD):   -0.552
Fu: 60.572%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.994
OATP1B3 inhibitor:   0.998 BCRP inhibitor:   0.053
BSEP inhibitor:   0.007

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.001 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.001 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.001 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.145
HLM stability:   0.034
?
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):  1.662 Half-life (T1/2):  2.975

ADMET: Toxicity

hERG Blockers:  0.017 hERG Blockers (10um):  0.068
Human Hepatotoxicity (H-HT):  0.585 Drug-induced Liver Injury (DILI):  0.98
AMES Toxicity:  0.937 Rat Oral Acute Toxicity:  0.042
Maximum Recommended Daily Dose:  0.14 Skin Sensitization:  1.0
Carcinogencity:  0.143 Eye Corrosion:  0.0
Eye Irritation:  0.226 Respiratory Toxicity:  0.029
Drug-induced Neurotoxicity:  0.023 Ototoxicity:  0.985
Hematotoxicity:  0.619 Drug-induced Nephrotoxicity:  0.936
Genotoxicity:  0.362 RPMI-8226 Immunitoxicity:  0.144
A549 Cytotoxicity:  0.399 Hek293 Cytotoxicity:  0.144
BCF:   0.157
?
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:   2.301
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   3.841
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.004
?
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
NPO10548 Stephania viridiflavens Species Menispermaceae Eukaryota n.a. root n.a. PMID[20645211]
NPO33136 sarracenia purpurea Species Sarraceniaceae Eukaryota n.a. n.a. n.a. PMID[22738356]
NPO14197 Patrinia scabra Species Caprifoliaceae Eukaryota Roots n.a. n.a. PMID[23002924]
NPO11907 Streptomyces nitrosporeus Species Streptomycetaceae Bacteria n.a. n.a. n.a. PMID[25304895]
NPO12588 Cornus officinalis Species Cornaceae Eukaryota Fruits n.a. n.a. PMID[29140705]
NPO14197 Patrinia scabra Species Caprifoliaceae Eukaryota Roots n.a. n.a. PMID[29799195]
NPO11907 Streptomyces nitrosporeus Species Streptomycetaceae Bacteria n.a. n.a. n.a. PMID[8609080]
NPO12588 Cornus officinalis Species Cornaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11907 Streptomyces nitrosporeus Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO8254 Melicope lasioneura Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12588 Cornus officinalis Species Cornaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO10548 Stephania viridiflavens Species Menispermaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO14197 Patrinia scabra Species Caprifoliaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO12588 Cornus officinalis Species Cornaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO14197 Patrinia scabra Species Caprifoliaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO10548 Stephania viridiflavens Species Menispermaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO12588 Cornus officinalis Species Cornaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO10548 Stephania viridiflavens Species Menispermaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO12588 Cornus officinalis Species Cornaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO12588 Cornus officinalis Species Cornaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11907 Streptomyces nitrosporeus Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO10458 Pithecollobium dulce n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO14197 Patrinia scabra Species Caprifoliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6207 Porthetria dispar n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO10548 Stephania viridiflavens Species Menispermaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8254 Melicope lasioneura Species Rutaceae 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
NPT38 Individual protein Signal transducer and activator of transcription 3 Homo sapiens IC50 = 6900.0 nM PMID[29140705]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT165 Cell line HeLa Homo sapiens IC50 > 50000.0 nM PMID[23002924]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 > 50000.0 nM PMID[23002924]

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 NPC65665 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 NPC231710
1.0 High Similarity NPC270908
0.7419 Intermediate Similarity NPC470573
0.7419 Intermediate Similarity NPC120021
0.7419 Intermediate Similarity NPC216826
0.7188 Intermediate Similarity NPC488472
0.7188 Intermediate Similarity NPC257424
0.6719 Remote Similarity NPC27687
0.6667 Remote Similarity NPC35185
0.6667 Remote Similarity NPC4899
0.6667 Remote Similarity NPC177013
0.6571 Remote Similarity NPC488456
0.6571 Remote Similarity NPC488471
0.6571 Remote Similarity NPC488466
0.6571 Remote Similarity NPC488465
0.6571 Remote Similarity NPC488460
0.6571 Remote Similarity NPC488462
0.6508 Remote Similarity NPC474730
0.6508 Remote Similarity NPC117596
0.6479 Remote Similarity NPC488470
0.6462 Remote Similarity NPC37240
0.6406 Remote Similarity NPC255677
0.6406 Remote Similarity NPC22149
0.6406 Remote Similarity NPC306344
0.6389 Remote Similarity NPC488457
0.6389 Remote Similarity NPC488464
0.6389 Remote Similarity NPC488463
0.6324 Remote Similarity NPC41681
0.6212 Remote Similarity NPC106668
0.6154 Remote Similarity NPC475928
0.6061 Remote Similarity NPC148270
0.6 Remote Similarity NPC170432
0.5974 Remote Similarity NPC488467
0.5942 Remote Similarity NPC222062
0.5909 Remote Similarity NPC307699
0.5823 Remote Similarity NPC488468
0.5811 Remote Similarity NPC488459
0.5789 Remote Similarity NPC488461
0.5789 Remote Similarity NPC488458
0.5735 Remote Similarity NPC61201
0.5672 Remote Similarity NPC195510
0.5672 Remote Similarity NPC298255
0.5672 Remote Similarity NPC13171
0.5616 Remote Similarity NPC197541
0.5616 Remote Similarity NPC234304
0.5616 Remote Similarity NPC118761
0.5571 Remote Similarity NPC475851
0.5571 Remote Similarity NPC475924
0.5522 Remote Similarity NPC303451
0.5522 Remote Similarity NPC72358
0.5493 Remote Similarity NPC254538
0.5429 Remote Similarity NPC193741
0.5352 Remote Similarity NPC609500
0.5309 Remote Similarity NPC488469
0.5286 Remote Similarity NPC110701
0.5224 Remote Similarity NPC63897

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC65665 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
NPD

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