Natural Product: NPC61630

Natural Product IDNPC61630
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (6R,9R)-Roseoside
IUPAC Name (4R)-4-hydroxy-3,5,5-trimethyl-4-[(E,3R)-3-[(2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxybut-1-enyl]cyclohex-2-en-1-one
Synonyms (6R,9R)-Roseoside
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL465921
PubChem CID 44570408
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0003909] Fatty Acyls
        • [CHEMONTID:0001766] Fatty acyl glycosides
          • [CHEMONTID:0003861] Fatty acyl glycosides of mono- and disaccharides

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 SWYRVCGNMNAFEK-QVRJGIIPSA-N
Standard InCHI InChI=1S/C19H30O8/c1-10-7-12(21)8-18(3,4)19(10,25)6-5-11(2)26-17-16(24)15(23)14(22)13(9-20)27-17/h5-7,11,13-17,20,22-25H,8-9H2,1-4H3/b6-5+/t11-,13-,14-,15+,16-,17-,19+/m1/s1
SMILES CC1=CC(=O)CC(C)(C)[C@@]1(/C=C/[C@@H](C)O[C@H]1[C@@H]([C@H]([C@@H]([C@@H](CO)O1)O)O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   386.19 Volume:   382.48
?
Van der Waals volume.
Dense:   1.01 LogP:   0.072
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   0.59
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -1.677
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The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   14.0
TPSA:   136.68
?
Topological Polar Surface Area.
 H-Bond Acceptor:   8.0
H-Bond Donor:   5.0 Rings:   2.0
Heavy Atoms:   8.0

MedChem Properties

QED Drug-Likeness Score:   0.396 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.753 Fsp3:   0.737
MCE-18:   49.697
?
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:   0 PAINS Alert:   0
Colloidal aggregators:   0.462 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.021
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.004
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.268 Promiscuous compounds:   0.433

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.859 MDCK Permeability:   -5.05
Pgp-inhibitor:   0.0 Pgp-substrate:   0.036
PAMPA:   0.995
?
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):   0.149
20% Bioavailability (F20%):   0.655 30% Bioavailability (F30%):   0.999
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.05
Plasma Protein Binding (PPB):   46.523% Volume Distribution (VD):   -0.517
Fu: 54.638%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.005
BSEP inhibitor:   0.057

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.003
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.001
CYP3A4-inhibitor:   0.097 CYP3A4-substrate:   0.004
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.482
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):  3.394 Half-life (T1/2):  2.066

ADMET: Toxicity

hERG Blockers:  0.013 hERG Blockers (10um):  0.094
Human Hepatotoxicity (H-HT):  0.714 Drug-induced Liver Injury (DILI):  0.747
AMES Toxicity:  0.888 Rat Oral Acute Toxicity:  0.1
Maximum Recommended Daily Dose:  0.067 Skin Sensitization:  0.995
Carcinogencity:  0.433 Eye Corrosion:  0.0
Eye Irritation:  0.327 Respiratory Toxicity:  0.041
Drug-induced Neurotoxicity:  0.113 Ototoxicity:  0.916
Hematotoxicity:  0.373 Drug-induced Nephrotoxicity:  0.762
Genotoxicity:  0.776 RPMI-8226 Immunitoxicity:  0.149
A549 Cytotoxicity:  0.305 Hek293 Cytotoxicity:  0.207
BCF:   0.365
?
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:   3.029
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.528
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.575
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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
NPO22821.1 Chamaecyparis obtusa var. formosana Varieties Cupressaceae Eukaryota n.a. n.a. n.a. PMID[25026733]
NPO28762 Alstonia angustifolia Species Apocynaceae Eukaryota bark and leaf Pahang, Malaysia n.a. PMID[25211145]
NPO28762 Alstonia angustifolia Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28621 Sepedonium ampullosporum Species Hypocreaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29108 Strychnos pseudoquina Species Loganiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO6724 Glycosmis stenocarpa Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO6724 Glycosmis stenocarpa Species Rutaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO28762 Alstonia angustifolia Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO6724 Glycosmis stenocarpa Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO6724 Glycosmis stenocarpa Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22821.1 Chamaecyparis obtusa var. formosana Varieties Cupressaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29108 Strychnos pseudoquina Species Loganiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28621 Sepedonium ampullosporum Species Hypocreaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29479 Epilobium rosmarinifolium Species Onagraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28762 Alstonia angustifolia Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29431 Rhapis humilis Species Arecaceae 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
NPT2 Others Unspecified n.a. Inhibition = 22.9 % PMID[19026550]

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 NPC61630 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 NPC169468
1.0 High Similarity NPC81483
1.0 High Similarity NPC307517
0.7143 Intermediate Similarity NPC474194
0.6545 Remote Similarity NPC25701
0.6545 Remote Similarity NPC2003
0.6491 Remote Similarity NPC223834
0.6 Remote Similarity NPC154127
0.5593 Remote Similarity NPC606634
0.5556 Remote Similarity NPC46407
0.5424 Remote Similarity NPC471756
0.5161 Remote Similarity NPC108141
0.5082 Remote Similarity NPC71381
0.5082 Remote Similarity NPC263407

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC61630 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