Natural Product: NPC601368

Natural Product IDNPC601368
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 BGSVZFQQTPFVTB-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL5424233
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic 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 BGSVZFQQTPFVTB-UHFFFAOYSA-N
Standard InCHI InChI=1S/C16H12O4/c1-8-3-4-9-11(7-8)15(19)13-10(14(9)18)5-6-12(17)16(13)20-2/h3-7,17H,1-2H3
SMILES COc1c(O)ccc2c1C(=O)c1cc(C)ccc1C2=O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   268.07 Volume:   273.692
?
Van der Waals volume.
Dense:   0.979 LogP:   3.413
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.176
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.534
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   18.0
TPSA:   63.6
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   1.0 Rings:   3.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.736 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.13 Fsp3:   0.125
MCE-18:   36.0
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Accepted GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   1 PAINS Alert:   1
Colloidal aggregators:   0.227 Fluc inhibitor:   0.667
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.201
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.598
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.503 Promiscuous compounds:   0.148

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.674 MDCK Permeability:   -4.707
Pgp-inhibitor:   0.95 Pgp-substrate:   0.103
PAMPA:   0.51
?
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):   0.056
20% Bioavailability (F20%):   0.137 30% Bioavailability (F30%):   0.616
50% Bioavailability (F50%):   0.962

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.011 MRP1:   0.771
Plasma Protein Binding (PPB):   97.727% Volume Distribution (VD):   -0.005
Fu: 1.746%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.97
OATP1B3 inhibitor:   0.975 BCRP inhibitor:   0.147
BSEP inhibitor:   0.827

ADMET: Metabolism

CYP1A2-inhibitor:   0.997 CYP1A2-substrate:   0.052
CYP2C19-inhibitor:   0.451 CYP2C19-substrate:   0.191
CYP2C9-inhibitor:   0.01 CYP2C9-substrate:   0.082
CYP2D6-inhibitor:   0.05 CYP2D6-substrate:   0.801
CYP3A4-inhibitor:   0.023 CYP3A4-substrate:   0.736
CYP2B6-substrate:   0.077 CYP2C8-inhibitor:   0.962
HLM stability:   0.38
?
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):  6.679 Half-life (T1/2):  1.075

ADMET: Toxicity

hERG Blockers:  0.138 hERG Blockers (10um):  0.617
Human Hepatotoxicity (H-HT):  0.658 Drug-induced Liver Injury (DILI):  0.833
AMES Toxicity:  0.846 Rat Oral Acute Toxicity:  0.407
Maximum Recommended Daily Dose:  0.309 Skin Sensitization:  0.856
Carcinogencity:  0.868 Eye Corrosion:  0.039
Eye Irritation:  0.986 Respiratory Toxicity:  0.684
Drug-induced Neurotoxicity:  0.597 Ototoxicity:  0.32
Hematotoxicity:  0.736 Drug-induced Nephrotoxicity:  0.421
Genotoxicity:  0.461 RPMI-8226 Immunitoxicity:  0.133
A549 Cytotoxicity:  0.498 Hek293 Cytotoxicity:  0.363
BCF:   1.312
?
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:   4.022
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.874
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.589
?
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]
NPO48953 Morinda citrifolia L. Genus 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
NPT393 Cell line HCT-116 Homo sapiens IC50 > 10000.0 nM PMID[38630559]
NPT171 Cell line MRC5 Homo sapiens IC50 > 10000.0 nM PMID[38630559]
NPT65 Cell line HepG2 Homo sapiens IC50 > 10000.0 nM PMID[38630559]

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 NPC601368 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
0.75 Intermediate Similarity NPC160777
0.6304 Remote Similarity NPC178976
0.625 Remote Similarity NPC118427
0.6042 Remote Similarity NPC164912
0.5909 Remote Similarity NPC605671
0.587 Remote Similarity NPC610476
0.5581 Remote Similarity NPC201542
0.5581 Remote Similarity NPC293367
0.5238 Remote Similarity NPC604031
0.5208 Remote Similarity NPC311740
0.5192 Remote Similarity NPC234331

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC601368 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