Natural Product: NPC601844

Natural Product IDNPC601844
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 VFZYLYJWCROVLO-DZGCQCFKSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL3039234
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 VFZYLYJWCROVLO-DZGCQCFKSA-N
Standard InCHI InChI=1S/C15H14O5/c16-10-3-1-8-5-13(19)15(20-14(8)7-10)9-2-4-11(17)12(18)6-9/h1-4,6-7,13,15-19H,5H2/t13-,15+/m0/s1
SMILES Oc1ccc2c(c1)O[C@H](c1ccc(O)c(O)c1)[C@@H](O)C2

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   274.08 Volume:   270.459
?
Van der Waals volume.
Dense:   1.013 LogP:   1.552
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.853
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.741
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   17.0
TPSA:   90.15
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   4.0 Rings:   3.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.596 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.137 Fsp3:   0.2
MCE-18:   56.667
?
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:   1 PAINS Alert:   1
Colloidal aggregators:   0.597 Fluc inhibitor:   0.608
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.04
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.069
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.485 Promiscuous compounds:   0.315

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.925 MDCK Permeability:   -4.895
Pgp-inhibitor:   0.001 Pgp-substrate:   0.054
PAMPA:   0.141
?
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):   0.003
20% Bioavailability (F20%):   0.91 30% Bioavailability (F30%):   0.995
50% Bioavailability (F50%):   0.995

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.13 MRP1:   0.769
Plasma Protein Binding (PPB):   82.183% Volume Distribution (VD):   0.088
Fu: 27.122%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   0.128
BSEP inhibitor:   0.109

ADMET: Metabolism

CYP1A2-inhibitor:   0.009 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.002 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.001 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.001 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.002 CYP3A4-substrate:   0.997
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.986
HLM stability:   0.0
?
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):  18.277 Half-life (T1/2):  2.59

ADMET: Toxicity

hERG Blockers:  0.197 hERG Blockers (10um):  0.693
Human Hepatotoxicity (H-HT):  0.591 Drug-induced Liver Injury (DILI):  0.229
AMES Toxicity:  0.385 Rat Oral Acute Toxicity:  0.226
Maximum Recommended Daily Dose:  0.726 Skin Sensitization:  0.957
Carcinogencity:  0.231 Eye Corrosion:  0.116
Eye Irritation:  0.989 Respiratory Toxicity:  0.513
Drug-induced Neurotoxicity:  0.12 Ototoxicity:  0.705
Hematotoxicity:  0.049 Drug-induced Nephrotoxicity:  0.076
Genotoxicity:  0.883 RPMI-8226 Immunitoxicity:  0.016
A549 Cytotoxicity:  0.519 Hek293 Cytotoxicity:  0.511
BCF:   1.061
?
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:   3.04
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.167
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.886
?
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
NPO6062 Acacia mearnsii Species Fabaceae Eukaryota n.a. bark n.a. PMID[21192716]
NPO12013 Colophospermum mopane Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[26444248]
NPO60312 Acacia melanoxylon Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO42311 Acacia spp. Genus Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29467 Virola elongata Species Myristicaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO6062 Acacia mearnsii Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12013 Colophospermum mopane Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO6487 Peltophorum africanum Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO43926 Virola minutifolia Genus Myristicaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO6062 Acacia mearnsii Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO6062 Acacia mearnsii Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO12013 Colophospermum mopane Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO6062 Acacia mearnsii Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29467 Virola elongata Species Myristicaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6487 Peltophorum africanum Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12013 Colophospermum mopane Species Fabaceae 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
NPT72 Individual protein Solute carrier organic anion transporter family member 1B3 Homo sapiens Inhibition = 95.23 % PMID[23571415]
NPT73 Individual protein Solute carrier organic anion transporter family member 1B1 Homo sapiens Inhibition = 74.52 % PMID[23571415]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT19 Organism Escherichia coli Escherichia coli MIC >= 1024.0 ug.mL-1 PMID[36731248]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC >= 1024.0 ug.mL-1 PMID[36731248]

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 NPC601844 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
0.6875 Remote Similarity NPC261619
0.6875 Remote Similarity NPC61477
0.6875 Remote Similarity NPC78770
0.6875 Remote Similarity NPC219876
0.6875 Remote Similarity NPC126029
0.6875 Remote Similarity NPC15658
0.6604 Remote Similarity NPC482704
0.64 Remote Similarity NPC246328
0.64 Remote Similarity NPC27532
0.5932 Remote Similarity NPC82917
0.58 Remote Similarity NPC207179
0.58 Remote Similarity NPC167571
0.58 Remote Similarity NPC278552
0.5645 Remote Similarity NPC313116
0.5645 Remote Similarity NPC603340
0.5625 Remote Similarity NPC93398
0.5625 Remote Similarity NPC258979
0.5625 Remote Similarity NPC8283
0.5556 Remote Similarity NPC36835
0.5556 Remote Similarity NPC246162
0.5556 Remote Similarity NPC9743
0.5556 Remote Similarity NPC260491
0.5556 Remote Similarity NPC61506
0.5556 Remote Similarity NPC240476
0.5469 Remote Similarity NPC70409
0.5469 Remote Similarity NPC204770
0.5469 Remote Similarity NPC600551
0.5469 Remote Similarity NPC601980
0.5469 Remote Similarity NPC602065
0.5469 Remote Similarity NPC611024
0.541 Remote Similarity NPC58190
0.541 Remote Similarity NPC108811
0.541 Remote Similarity NPC170103
0.541 Remote Similarity NPC236202
0.541 Remote Similarity NPC262911
0.541 Remote Similarity NPC202742
0.5357 Remote Similarity NPC178054
0.5323 Remote Similarity NPC246202
0.5323 Remote Similarity NPC224161
0.5323 Remote Similarity NPC46335
0.5323 Remote Similarity NPC294558
0.5323 Remote Similarity NPC18185
0.5323 Remote Similarity NPC263940
0.5323 Remote Similarity NPC279406
0.5323 Remote Similarity NPC486519
0.5303 Remote Similarity NPC600630
0.5303 Remote Similarity NPC607896
0.5303 Remote Similarity NPC611369
0.5192 Remote Similarity NPC268266
0.5192 Remote Similarity NPC42760
0.5192 Remote Similarity NPC220825
0.5192 Remote Similarity NPC268342
0.5185 Remote Similarity NPC325028
0.5185 Remote Similarity NPC256346
0.5185 Remote Similarity NPC103799
0.5185 Remote Similarity NPC606550
0.5172 Remote Similarity NPC150670
0.5156 Remote Similarity NPC28440

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC601844 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
0.6875 Remote Similarity NPD1612 Clinical (unspecified phase)
0.6875 Remote Similarity NPD1613 Phase 4

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