Natural Product: NPC605699

Natural Product IDNPC605699
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 UVVWQQKSNZLUQA-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1221517
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0004603] Organic oxygen compounds
      • [CHEMONTID:0000323] Organooxygen compounds
        • [CHEMONTID:0001831] Carbonyl compounds
          • [CHEMONTID:0000118] Ketones
            • [CHEMONTID:0003670] Aryl ketones
              • [CHEMONTID:0004296] Phenylketones
                • [CHEMONTID:0004298] Alkyl-phenylketones

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 UVVWQQKSNZLUQA-UHFFFAOYSA-N
Standard InCHI InChI=1S/C18H26O5/c1-3-5-6-7-8-9-15(20)18-13(11-17(22)23-4-2)10-14(19)12-16(18)21/h10,12,19,21H,3-9,11H2,1-2H3
SMILES CCCCCCCC(=O)c1c(O)cc(O)cc1CC(=O)OCC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   322.18 Volume:   342.097
?
Van der Waals volume.
Dense:   0.942 LogP:   4.537
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.502
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.543
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   11.0 Rigid Bonds:   8.0
TPSA:   83.83
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   2.0 Rings:   1.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.389 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.345 Fsp3:   0.556
MCE-18:   9.0
?
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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.135 Fluc inhibitor:   0.087
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.116
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.209
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.607 Promiscuous compounds:   0.243

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.053 MDCK Permeability:   -4.651
Pgp-inhibitor:   0.061 Pgp-substrate:   0.017
PAMPA:   0.066
?
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):   0.016
20% Bioavailability (F20%):   0.089 30% Bioavailability (F30%):   0.379
50% Bioavailability (F50%):   0.627

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.01 MRP1:   0.891
Plasma Protein Binding (PPB):   96.372% Volume Distribution (VD):   0.351
Fu: 4.292%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.574
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.081
BSEP inhibitor:   0.829

ADMET: Metabolism

CYP1A2-inhibitor:   0.92 CYP1A2-substrate:   0.998
CYP2C19-inhibitor:   0.208 CYP2C19-substrate:   0.621
CYP2C9-inhibitor:   0.313 CYP2C9-substrate:   0.627
CYP2D6-inhibitor:   0.009 CYP2D6-substrate:   1.0
CYP3A4-inhibitor:   0.001 CYP3A4-substrate:   0.995
CYP2B6-substrate:   0.001 CYP2C8-inhibitor:   1.0
HLM stability:   0.979
?
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):  3.141 Half-life (T1/2):  0.946

ADMET: Toxicity

hERG Blockers:  0.129 hERG Blockers (10um):  0.777
Human Hepatotoxicity (H-HT):  0.243 Drug-induced Liver Injury (DILI):  0.244
AMES Toxicity:  0.13 Rat Oral Acute Toxicity:  0.364
Maximum Recommended Daily Dose:  0.263 Skin Sensitization:  0.899
Carcinogencity:  0.199 Eye Corrosion:  0.342
Eye Irritation:  0.988 Respiratory Toxicity:  0.928
Drug-induced Neurotoxicity:  0.141 Ototoxicity:  0.118
Hematotoxicity:  0.093 Drug-induced Nephrotoxicity:  0.198
Genotoxicity:  0.017 RPMI-8226 Immunitoxicity:  0.03
A549 Cytotoxicity:  0.083 Hek293 Cytotoxicity:  0.213
BCF:   1.705
?
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:   4.436
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.67
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.028
?
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
NPO44779 Diaporthe sp CR146 Genus Diaporthaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO44545 Dothiorella sp. Species Botryosphaeriaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO42712 Phomopsis sp. ZSU-H76 Genus Diaporthaceae Eukaryota 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
NPT28442 Single protein Nuclear receptor subfamily 4 group A member 2 Homo sapiens Activity n.a. n.a. n.a. PMID[33289551]
NPT28442 Single protein Nuclear receptor subfamily 4 group A member 2 Homo sapiens Activity n.a. n.a. n.a. PMID[18690216]
NPT22141 Single protein Nuclear receptor subfamily 4 group A member 1 Homo sapiens Kd = 1510.0 nM PMID[18690216]
NPT29439 Single protein Nuclear receptor subfamily 4 group A member 1 Mus musculus Activity n.a. n.a. n.a. PMID[18690216]
NPT22141 Single protein Nuclear receptor subfamily 4 group A member 1 Homo sapiens Activity n.a. n.a. n.a. PMID[18690216]
NPT29439 Single protein Nuclear receptor subfamily 4 group A member 1 Mus musculus FC = 6.23 n.a. PMID[18690216]
NPT29439 Single protein Nuclear receptor subfamily 4 group A member 1 Mus musculus FC = 3.05 n.a. PMID[18690216]
NPT22141 Single protein Nuclear receptor subfamily 4 group A member 1 Homo sapiens Activity n.a. n.a. n.a. PMID[33289551]
NPT22141 Single protein Nuclear receptor subfamily 4 group A member 1 Homo sapiens EC50 = 0.115 nM PMID[34251209]
NPT22141 Single protein Nuclear receptor subfamily 4 group A member 1 Homo sapiens Ratio = 12.5 n.a. PMID[24795803]
NPT22141 Single protein Nuclear receptor subfamily 4 group A member 1 Homo sapiens EC50 = 0.278 nM PMID[34251209]
NPT22141 Single protein Nuclear receptor subfamily 4 group A member 1 Homo sapiens EC50 = 0.278 nM PMID[18690216]
NPT22141 Single protein Nuclear receptor subfamily 4 group A member 1 Homo sapiens Activity n.a. n.a. n.a. PMID[24795803]
NPT29439 Single protein Nuclear receptor subfamily 4 group A member 1 Mus musculus FC = 3.0 n.a. PMID[18690216]
NPT22141 Single protein Nuclear receptor subfamily 4 group A member 1 Homo sapiens Kd = 740.0 nM PMID[18690216]
NPT22141 Single protein Nuclear receptor subfamily 4 group A member 1 Homo sapiens EC50 = 0.115 nM PMID[18690216]
NPT29439 Single protein Nuclear receptor subfamily 4 group A member 1 Mus musculus FC = 5.0 n.a. PMID[18690216]
NPT22141 Single protein Nuclear receptor subfamily 4 group A member 1 Homo sapiens Kd = 720.0 nM PMID[18690216]
NPT28605 Single protein Nuclear receptor subfamily 4 group A member 3 Homo sapiens Activity n.a. n.a. n.a. PMID[33289551]
NPT28605 Single protein Nuclear receptor subfamily 4 group A member 3 Homo sapiens Activity n.a. n.a. n.a. PMID[18690216]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT547 Cell line BGC-823 Homo sapiens Activity n.a. n.a. n.a. PMID[18690216]
NPT681 Cell line PC-12 Rattus norvegicus Activity n.a. n.a. n.a. PMID[33289551]
NPT858 Cell line LNCaP Homo sapiens IC50 = 13400.0 nM PMID[24795803]
NPT858 Cell line LNCaP Homo sapiens Inhibition = 76.0 % PMID[24795803]
NPT2615 Cell line HEK-293T Homo sapiens Activity n.a. n.a. n.a. PMID[33289551]
NPT397 Cell line NCI-H460 Homo sapiens FC = 4.4 n.a. PMID[24795803]
NPT547 Cell line BGC-823 Homo sapiens Activity = 63.0 % PMID[24795803]
NPT65 Cell line HepG2 Homo sapiens Activity n.a. n.a. n.a. PMID[18690216]
NPT397 Cell line NCI-H460 Homo sapiens Activity n.a. n.a. n.a. PMID[24795803]
NPT547 Cell line BGC-823 Homo sapiens Activity = 63.5 % PMID[18690216]
NPT323 Cell line SW-620 Homo sapiens Inhibition > 70.0 % PMID[18690216]
NPT886 Cell line NIH3T3 Mus musculus Inhibition n.a. n.a. % PMID[18690216]
NPT547 Cell line BGC-823 Homo sapiens Activity = 20.1 % PMID[18690216]
NPT28438 Unchecked Unchecked n.a. Activity n.a. n.a. n.a. PMID[33289551]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Activity = 50.0 % PMID[24795803]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition n.a. n.a. % PMID[18690216]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition = 88.0 % PMID[24795803]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 15300.0 nM PMID[24795803]
NPT88 Organism Mycobacterium tuberculosis Mycobacterium tuberculosis IC50 = 250.0 ug.mL-1 PMID[18690216]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition >= 40.0 % PMID[18690216]
NPT312 Organism Saccharomyces cerevisiae Saccharomyces cerevisiae IC50 = 1.56 ug.mL-1 PMID[18690216]
NPT17 Organism Staphylococcus epidermidis Staphylococcus epidermidis MIC = 21.0 ug.mL-1 PMID[37875020]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus IC50 = 12.5 ug.mL-1 PMID[18690216]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC = 18.0 ug.mL-1 PMID[37875020]
NPT747 Organism Acinetobacter baumannii Acinetobacter baumannii GI = 51.0 % PMID[37875020]
NPT30059 Cell line SK-N-BE(2) Homo sapiens Activity n.a. n.a. n.a. PMID[33289551]

In vivo activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT32 Organism Mus musculus Mus musculus FC = 3.0 n.a. PMID[18690216]
NPT32 Organism Mus musculus Mus musculus Activity = 3.7 mM PMID[18690216]
NPT32 Organism Mus musculus Mus musculus Activity n.a. n.a. n.a. PMID[18690216]
NPT32 Organism Mus musculus Mus musculus Activity = 3.2 mM PMID[18690216]





 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 NPC605699 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
0.7451 Intermediate Similarity NPC178467
0.7451 Intermediate Similarity NPC474771
0.6545 Remote Similarity NPC607219
0.5714 Remote Similarity NPC164870
0.5593 Remote Similarity NPC474849
0.5593 Remote Similarity NPC65837
0.5593 Remote Similarity NPC149372
0.55 Remote Similarity NPC475974
0.5345 Remote Similarity NPC474655
0.5217 Remote Similarity NPC275837
0.5192 Remote Similarity NPC473691
0.5192 Remote Similarity NPC477454
0.5179 Remote Similarity NPC476389
0.5167 Remote Similarity NPC177307
0.5167 Remote Similarity NPC9121
0.5082 Remote Similarity NPC354984

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC605699 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