Natural Product: NPC475928

Natural Product IDNPC475928
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Epi-Dihydrocornin
IUPAC Name methyl (1S,4aS,5S,7S,7aR)-5-hydroxy-7-methyl-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 Epi-Dihydrocornin
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL518727
PubChem CID 44583983
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 MTMCJGRBRGDLOQ-QCBYNKRRSA-N
Standard InCHI InChI=1S/C17H26O10/c1-6-3-8(19)11-7(15(23)24-2)5-25-16(10(6)11)27-17-14(22)13(21)12(20)9(4-18)26-17/h5-6,8-14,16-22H,3-4H2,1-2H3/t6-,8-,9+,10+,11-,12+,13-,14+,16-,17-/m0/s1
SMILES OC[C@H]1O[C@@H](O[C@@H]2OC=C([C@@H]3[C@H]2[C@@H](C)C[C@@H]3O)C(=O)OC)[C@@H]([C@H]([C@@H]1O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   390.15 Volume:   359.548
?
Van der Waals volume.
Dense:   1.085 LogP:   -0.918
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   -0.436
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -0.674
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   17.0
TPSA:   155.14
?
Topological Polar Surface Area.
 H-Bond Acceptor:   10.0
H-Bond Donor:   5.0 Rings:   3.0
Heavy Atoms:   10.0

MedChem Properties

QED Drug-Likeness Score:   0.336 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.744 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:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.441 Fluc inhibitor:   0.001
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.185
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.0
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.248 Promiscuous compounds:   0.213

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.736 MDCK Permeability:   -5.185
Pgp-inhibitor:   0.001 Pgp-substrate:   0.557
PAMPA:   0.965
?
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):   0.414
20% Bioavailability (F20%):   0.185 30% Bioavailability (F30%):   0.954
50% Bioavailability (F50%):   0.93

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.1 MRP1:   0.865
Plasma Protein Binding (PPB):   35.26% Volume Distribution (VD):   -0.563
Fu: 66.655%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.998
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   0.069
BSEP inhibitor:   0.005

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.001
CYP3A4-inhibitor:   0.002 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.265
HLM stability:   0.018
?
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):  1.493 Half-life (T1/2):  3.391

ADMET: Toxicity

hERG Blockers:  0.02 hERG Blockers (10um):  0.117
Human Hepatotoxicity (H-HT):  0.591 Drug-induced Liver Injury (DILI):  0.881
AMES Toxicity:  0.809 Rat Oral Acute Toxicity:  0.028
Maximum Recommended Daily Dose:  0.02 Skin Sensitization:  0.989
Carcinogencity:  0.185 Eye Corrosion:  0.0
Eye Irritation:  0.192 Respiratory Toxicity:  0.015
Drug-induced Neurotoxicity:  0.02 Ototoxicity:  0.973
Hematotoxicity:  0.502 Drug-induced Nephrotoxicity:  0.823
Genotoxicity:  0.141 RPMI-8226 Immunitoxicity:  0.08
A549 Cytotoxicity:  0.059 Hek293 Cytotoxicity:  0.069
BCF:   0.264
?
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:   2.613
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.212
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.276
?
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 DrugMatrix in vivo data: Hematology

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 NPC475928 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
0.7414 Intermediate Similarity NPC170432
0.7288 Intermediate Similarity NPC35185
0.7288 Intermediate Similarity NPC4899
0.7288 Intermediate Similarity NPC177013
0.7119 Intermediate Similarity NPC474730
0.7049 Intermediate Similarity NPC106668
0.6885 Remote Similarity NPC148270
0.6774 Remote Similarity NPC27687
0.6508 Remote Similarity NPC37240
0.6452 Remote Similarity NPC298255
0.629 Remote Similarity NPC117596
0.625 Remote Similarity NPC61201
0.619 Remote Similarity NPC255677
0.619 Remote Similarity NPC22149
0.619 Remote Similarity NPC306344
0.6154 Remote Similarity NPC231710
0.6154 Remote Similarity NPC470573
0.6154 Remote Similarity NPC120021
0.6154 Remote Similarity NPC216826
0.6154 Remote Similarity NPC270908
0.6154 Remote Similarity NPC65665
0.6 Remote Similarity NPC110701
0.597 Remote Similarity NPC488472
0.597 Remote Similarity NPC257424
0.5968 Remote Similarity NPC63897
0.5938 Remote Similarity NPC195510
0.5938 Remote Similarity NPC13171
0.5882 Remote Similarity NPC41681
0.5833 Remote Similarity NPC488470
0.5781 Remote Similarity NPC303451
0.5781 Remote Similarity NPC72358
0.5735 Remote Similarity NPC222062
0.5735 Remote Similarity NPC254538
0.5692 Remote Similarity NPC307699
0.5672 Remote Similarity NPC193741
0.5641 Remote Similarity NPC475379
0.5641 Remote Similarity NPC96599
0.5588 Remote Similarity NPC475851
0.5588 Remote Similarity NPC475924
0.5588 Remote Similarity NPC609500
0.5584 Remote Similarity NPC488467
0.5479 Remote Similarity NPC488456
0.5479 Remote Similarity NPC488471
0.5479 Remote Similarity NPC488466
0.5479 Remote Similarity NPC488465
0.5479 Remote Similarity NPC488460
0.5479 Remote Similarity NPC488462
0.5443 Remote Similarity NPC488468
0.5417 Remote Similarity NPC197541
0.5417 Remote Similarity NPC234304
0.5417 Remote Similarity NPC118761
0.5375 Remote Similarity NPC475484
0.5333 Remote Similarity NPC488457
0.5333 Remote Similarity NPC488464
0.5333 Remote Similarity NPC488463
0.5224 Remote Similarity NPC250545
0.5205 Remote Similarity NPC605627
0.5143 Remote Similarity NPC6414
0.5143 Remote Similarity NPC610085
0.5122 Remote Similarity NPC202391
0.5122 Remote Similarity NPC296659
0.5075 Remote Similarity NPC304163
0.5068 Remote Similarity NPC469543

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC475928 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