Natural Product: NPC474730

Natural Product IDNPC474730
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 6Alpha-Hydroxyadoxoside
IUPAC Name methyl (1S,4aS,6R,7S,7aS)-6-hydroxy-7-(hydroxymethyl)-1-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-1,4a,5,6,7,7a-hexahydrocyclopenta[c]pyran-4-carboxylate
Synonyms 6Alpha-Hydroxyadoxoside
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL480665
PubChem CID 44575383
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0000259] Prenol lipids
        • [CHEMONTID:0002049] Terpene glycosides
          • [CHEMONTID:0004081] Iridoid 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 GTEDLLYKAJRTNK-CBQOGAMZSA-N
Standard InCHI InChI=1S/C17H26O11/c1-25-15(24)8-5-26-16(11-6(8)2-9(20)7(11)3-18)28-17-14(23)13(22)12(21)10(4-19)27-17/h5-7,9-14,16-23H,2-4H2,1H3/t6-,7+,9-,10-,11+,12-,13+,14-,16+,17+/m1/s1
SMILES COC(=O)C1=COC(C2C1CC(C2CO)O)OC3C(C(C(C(O3)CO)O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   406.15 Volume:   368.338
?
Van der Waals volume.
Dense:   1.103 LogP:   -2.107
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   -1.357
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -0.42
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   17.0
TPSA:   175.37
?
Topological Polar Surface Area.
 H-Bond Acceptor:   11.0
H-Bond Donor:   6.0 Rings:   3.0
Heavy Atoms:   11.0

MedChem Properties

QED Drug-Likeness Score:   0.254 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.78 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:   Accepted
Pfizer Rule:   Rejected GSK Rule:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.002 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.052
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.072
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.261 Promiscuous compounds:   0.002

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.022 MDCK Permeability:   -5.299
Pgp-inhibitor:   0.0 Pgp-substrate:   0.885
PAMPA:   0.999
?
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):   0.993
20% Bioavailability (F20%):   0.8 30% Bioavailability (F30%):   0.995
50% Bioavailability (F50%):   0.993

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.018 MRP1:   0.957
Plasma Protein Binding (PPB):   22.776% Volume Distribution (VD):   -0.635
Fu: 84.232%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.0
OATP1B3 inhibitor:   0.651 BCRP inhibitor:   0.084
BSEP inhibitor:   0.012

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.005 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.988 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.001 CYP2D6-substrate:   0.001
CYP3A4-inhibitor:   0.002 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.001
HLM stability:   0.007
?
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):  1.673 Half-life (T1/2):  2.43

ADMET: Toxicity

hERG Blockers:  0.025 hERG Blockers (10um):  0.276
Human Hepatotoxicity (H-HT):  0.588 Drug-induced Liver Injury (DILI):  0.639
AMES Toxicity:  0.58 Rat Oral Acute Toxicity:  0.191
Maximum Recommended Daily Dose:  0.269 Skin Sensitization:  0.192
Carcinogencity:  0.205 Eye Corrosion:  0.0
Eye Irritation:  0.014 Respiratory Toxicity:  0.018
Drug-induced Neurotoxicity:  0.372 Ototoxicity:  0.989
Hematotoxicity:  0.073 Drug-induced Nephrotoxicity:  0.168
Genotoxicity:  0.082 RPMI-8226 Immunitoxicity:  0.037
A549 Cytotoxicity:  0.015 Hek293 Cytotoxicity:  0.264
BCF:   0.138
?
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:   1.782
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   3.587
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   2.514
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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
NPO4323 Morinda citrifolia Species Rubiaceae Eukaryota n.a. n.a. n.a. DOI[10.1016/j.jarmap.2018.11.004]
NPO4323 Morinda citrifolia Species Rubiaceae Eukaryota n.a. leaf n.a. PMID[11348221]
NPO4323 Morinda citrifolia Species Rubiaceae Eukaryota fruit n.a. n.a. PMID[15844957]
NPO4323 Morinda citrifolia Species Rubiaceae Eukaryota fruits n.a. n.a. PMID[16378361]
NPO4323 Morinda citrifolia Species Rubiaceae Eukaryota fruits Tahiti n.a. PMID[17378609]
NPO4323 Morinda citrifolia Species Rubiaceae Eukaryota Fruits n.a. n.a. PMID[17480098]
NPO4323 Morinda citrifolia Species Rubiaceae Eukaryota roots n.a. n.a. PMID[18076142]
NPO4323 Morinda citrifolia Species Rubiaceae Eukaryota n.a. n.a. n.a. PMID[24224843]
NPO4323 Morinda citrifolia Species Rubiaceae Eukaryota n.a. n.a. n.a. PMID[27196335]
NPO4323 Morinda citrifolia Species Rubiaceae Eukaryota Fruits n.a. n.a. PMID[32083868]
NPO4323 Morinda citrifolia Species Rubiaceae Eukaryota n.a. n.a. n.a. PMID[36014413]
NPO4323 Morinda citrifolia Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4323 Morinda citrifolia Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO4323 Morinda citrifolia Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO4323 Morinda citrifolia Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO4323 Morinda citrifolia Species Rubiaceae 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
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 > 30000.0 nM PMID[15844957]
NPT1 Others Radical scavenging activity n.a. IC50 > 30000.0 nM PMID[16562825]

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 NPC474730 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
0.8364 Intermediate Similarity NPC35185
0.8364 Intermediate Similarity NPC4899
0.8364 Intermediate Similarity NPC177013
0.7167 Intermediate Similarity NPC27687
0.7119 Intermediate Similarity NPC475928
0.6949 Remote Similarity NPC117596
0.6885 Remote Similarity NPC37240
0.6833 Remote Similarity NPC255677
0.6833 Remote Similarity NPC22149
0.6833 Remote Similarity NPC306344
0.6667 Remote Similarity NPC170432
0.6613 Remote Similarity NPC106668
0.6508 Remote Similarity NPC231710
0.6508 Remote Similarity NPC470573
0.6508 Remote Similarity NPC120021
0.6508 Remote Similarity NPC216826
0.6508 Remote Similarity NPC270908
0.6508 Remote Similarity NPC65665
0.6308 Remote Similarity NPC488472
0.6308 Remote Similarity NPC222062
0.6308 Remote Similarity NPC257424
0.6301 Remote Similarity NPC488467
0.629 Remote Similarity NPC195510
0.629 Remote Similarity NPC307699
0.629 Remote Similarity NPC13171
0.6212 Remote Similarity NPC41681
0.619 Remote Similarity NPC148270
0.6143 Remote Similarity NPC488470
0.6133 Remote Similarity NPC488468
0.6094 Remote Similarity NPC61201
0.6032 Remote Similarity NPC298255
0.5942 Remote Similarity NPC197541
0.5942 Remote Similarity NPC234304
0.5942 Remote Similarity NPC118761
0.5775 Remote Similarity NPC488456
0.5775 Remote Similarity NPC488471
0.5775 Remote Similarity NPC488466
0.5775 Remote Similarity NPC488465
0.5775 Remote Similarity NPC488460
0.5775 Remote Similarity NPC488462
0.5758 Remote Similarity NPC193741
0.5672 Remote Similarity NPC475851
0.5672 Remote Similarity NPC475924
0.5672 Remote Similarity NPC609500
0.5625 Remote Similarity NPC303451
0.5625 Remote Similarity NPC72358
0.5616 Remote Similarity NPC488457
0.5616 Remote Similarity NPC488464
0.5616 Remote Similarity NPC488463
0.5606 Remote Similarity NPC110701
0.5588 Remote Similarity NPC254538
0.5584 Remote Similarity NPC488469
0.557 Remote Similarity NPC202391
0.557 Remote Similarity NPC296659
0.5556 Remote Similarity NPC63897
0.5316 Remote Similarity NPC475379
0.5303 Remote Similarity NPC250545
0.5263 Remote Similarity NPC488461
0.5263 Remote Similarity NPC488458
0.5256 Remote Similarity NPC46641
0.525 Remote Similarity NPC475484
0.5125 Remote Similarity NPC96599
0.5077 Remote Similarity NPC482656
0.5075 Remote Similarity NPC170204
0.5068 Remote Similarity NPC605627
0.5067 Remote Similarity NPC488459

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC474730 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