Natural Product: NPC605229

Natural Product IDNPC605229
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 PWSUUSZLVOWNGI-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1170819
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 PWSUUSZLVOWNGI-UHFFFAOYSA-N
Standard InCHI InChI=1S/C17H14O5/c1-20-15-7-12-14(8-16(15)21-2)22-9-13(17(12)19)10-3-5-11(18)6-4-10/h3-9,18H,1-2H3
SMILES COc1cc2occ(-c3ccc(O)cc3)c(=O)c2cc1OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   298.08 Volume:   299.778
?
Van der Waals volume.
Dense:   0.994 LogP:   1.917
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.167
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.464
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   18.0
TPSA:   68.9
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   1.0 Rings:   3.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.804 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.039 Fsp3:   0.118
MCE-18:   17.0
?
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:   0.28 Fluc inhibitor:   0.971
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.952
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.576
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.422 Promiscuous compounds:   0.654

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.687 MDCK Permeability:   -4.664
Pgp-inhibitor:   0.224 Pgp-substrate:   0.049
PAMPA:   0.49
?
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):   0.075
20% Bioavailability (F20%):   0.301 30% Bioavailability (F30%):   0.181
50% Bioavailability (F50%):   0.838

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.003 MRP1:   0.671
Plasma Protein Binding (PPB):   89.496% Volume Distribution (VD):   0.063
Fu: 13.323%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.977
OATP1B3 inhibitor:   0.993 BCRP inhibitor:   0.894
BSEP inhibitor:   0.978

ADMET: Metabolism

CYP1A2-inhibitor:   0.985 CYP1A2-substrate:   0.987
CYP2C19-inhibitor:   0.025 CYP2C19-substrate:   0.941
CYP2C9-inhibitor:   0.844 CYP2C9-substrate:   0.332
CYP2D6-inhibitor:   0.999 CYP2D6-substrate:   0.795
CYP3A4-inhibitor:   0.028 CYP3A4-substrate:   0.944
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.993
HLM stability:   0.021
?
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):  8.615 Half-life (T1/2):  1.327

ADMET: Toxicity

hERG Blockers:  0.192 hERG Blockers (10um):  0.589
Human Hepatotoxicity (H-HT):  0.509 Drug-induced Liver Injury (DILI):  0.581
AMES Toxicity:  0.473 Rat Oral Acute Toxicity:  0.54
Maximum Recommended Daily Dose:  0.674 Skin Sensitization:  0.41
Carcinogencity:  0.757 Eye Corrosion:  0.202
Eye Irritation:  0.972 Respiratory Toxicity:  0.666
Drug-induced Neurotoxicity:  0.635 Ototoxicity:  0.244
Hematotoxicity:  0.216 Drug-induced Nephrotoxicity:  0.236
Genotoxicity:  0.696 RPMI-8226 Immunitoxicity:  0.07
A549 Cytotoxicity:  0.163 Hek293 Cytotoxicity:  0.497
BCF:   0.964
?
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:   3.597
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.431
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.966
?
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
NPO63181 Actinomycete isolate HKI 129-L n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO44160 Streptomyces sp. GW27/2506 Genus Streptomycetaceae Bacteria n.a. n.a. n.a. Database[COCONUT]

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. Inhibition n.a. n.a. % PMID[20627560]

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 NPC605229 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
0.74 Intermediate Similarity NPC120924
0.7358 Intermediate Similarity NPC181124
0.7358 Intermediate Similarity NPC100971
0.7037 Intermediate Similarity NPC216769
0.6923 Remote Similarity NPC195919
0.6909 Remote Similarity NPC487217
0.6769 Remote Similarity NPC259070
0.6667 Remote Similarity NPC105511
0.6429 Remote Similarity NPC186507
0.6429 Remote Similarity NPC162680
0.6429 Remote Similarity NPC303644
0.6333 Remote Similarity NPC62518
0.6316 Remote Similarity NPC148497
0.6296 Remote Similarity NPC182842
0.625 Remote Similarity NPC7013
0.625 Remote Similarity NPC269451
0.6038 Remote Similarity NPC234560
0.6 Remote Similarity NPC285973
0.5965 Remote Similarity NPC603503
0.5926 Remote Similarity NPC218490
0.5862 Remote Similarity NPC121522
0.5862 Remote Similarity NPC209560
0.5862 Remote Similarity NPC490700
0.569 Remote Similarity NPC131266
0.5667 Remote Similarity NPC12377
0.5636 Remote Similarity NPC125449
0.5574 Remote Similarity NPC139364
0.5538 Remote Similarity NPC219917
0.5536 Remote Similarity NPC182428
0.55 Remote Similarity NPC181209
0.55 Remote Similarity NPC279061
0.55 Remote Similarity NPC483565
0.5455 Remote Similarity NPC168085
0.5424 Remote Similarity NPC10467
0.541 Remote Similarity NPC52623
0.5357 Remote Similarity NPC39426
0.5352 Remote Similarity NPC211014
0.5333 Remote Similarity NPC203747
0.5333 Remote Similarity NPC609386
0.5333 Remote Similarity NPC610981
0.5323 Remote Similarity NPC80710
0.5278 Remote Similarity NPC161749
0.5254 Remote Similarity NPC185607
0.5238 Remote Similarity NPC134726
0.5231 Remote Similarity NPC260640
0.5211 Remote Similarity NPC135345
0.5167 Remote Similarity NPC116632
0.5167 Remote Similarity NPC474340
0.5161 Remote Similarity NPC262623
0.5152 Remote Similarity NPC97716
0.5135 Remote Similarity NPC205076
0.5082 Remote Similarity NPC245382
0.5082 Remote Similarity NPC136095
0.5082 Remote Similarity NPC69430
0.5082 Remote Similarity NPC294409
0.5082 Remote Similarity NPC490701
0.5079 Remote Similarity NPC487216
0.5079 Remote Similarity NPC191741

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC605229 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
0.5357 Remote Similarity NPD1510 Phase 2
0.5278 Remote Similarity NPD4381 Clinical (unspecified phase)

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