Natural Product: NPC600177

Natural Product IDNPC600177
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 MRQSJFKGZKPPNM-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL2268880
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 MRQSJFKGZKPPNM-UHFFFAOYSA-N
Standard InCHI InChI=1S/C17H14O6/c1-21-10-5-3-9(4-6-10)14-8-12(19)15-11(18)7-13(20)16(22-2)17(15)23-14/h3-8,18,20H,1-2H3
SMILES COc1ccc(-c2cc(=O)c3c(O)cc(O)c(OC)c3o2)cc1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   314.08 Volume:   308.569
?
Van der Waals volume.
Dense:   1.018 LogP:   2.861
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.693
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.542
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   18.0
TPSA:   89.13
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   2.0 Rings:   3.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.772 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.315 Fsp3:   0.118
MCE-18:   18.0
?
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:   1 PAINS Alert:   0
Colloidal aggregators:   0.408 Fluc inhibitor:   0.687
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.947
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.753
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.374 Promiscuous compounds:   0.713

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.083 MDCK Permeability:   -4.766
Pgp-inhibitor:   0.445 Pgp-substrate:   0.508
PAMPA:   0.163
?
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):   0.066
20% Bioavailability (F20%):   0.25 30% Bioavailability (F30%):   0.547
50% Bioavailability (F50%):   0.856

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.049 MRP1:   0.862
Plasma Protein Binding (PPB):   97.974% Volume Distribution (VD):   -0.276
Fu: 1.515%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.734
OATP1B3 inhibitor:   0.974 BCRP inhibitor:   0.902
BSEP inhibitor:   0.898

ADMET: Metabolism

CYP1A2-inhibitor:   0.179 CYP1A2-substrate:   0.672
CYP2C19-inhibitor:   0.002 CYP2C19-substrate:   0.191
CYP2C9-inhibitor:   0.995 CYP2C9-substrate:   0.919
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.965
CYP3A4-inhibitor:   0.012 CYP3A4-substrate:   0.56
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.832
?
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):  3.739 Half-life (T1/2):  1.301

ADMET: Toxicity

hERG Blockers:  0.08 hERG Blockers (10um):  0.448
Human Hepatotoxicity (H-HT):  0.402 Drug-induced Liver Injury (DILI):  0.875
AMES Toxicity:  0.663 Rat Oral Acute Toxicity:  0.436
Maximum Recommended Daily Dose:  0.687 Skin Sensitization:  0.368
Carcinogencity:  0.736 Eye Corrosion:  0.136
Eye Irritation:  0.981 Respiratory Toxicity:  0.888
Drug-induced Neurotoxicity:  0.115 Ototoxicity:  0.111
Hematotoxicity:  0.234 Drug-induced Nephrotoxicity:  0.172
Genotoxicity:  0.834 RPMI-8226 Immunitoxicity:  0.125
A549 Cytotoxicity:  0.282 Hek293 Cytotoxicity:  0.564
BCF:   1.096
?
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:   3.866
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.544
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.034
?
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
NPO19468 Madia sativa Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO51308 Calceolaria irazeunsis Genus Calceolariaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO45016 Eucryphia Genus Cunoniaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO50639 Chrysothamnus nauseosus Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO56287 Zinnia acerosa Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO61863 Bucegia romanica Species Marchantiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO59855 Eucryphia jinksii Species Cunoniaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO47809 Madia capitata Genus Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO52514 Scorzonera undulata Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19468 Madia sativa Species Asteraceae 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
NPT65 Cell line HepG2 Homo sapiens IC50 = 42400.0 nM PMID[31238183]
NPT65 Cell line HepG2 Homo sapiens IC50 = 42400.0 nM PMID[28117202]
NPT65 Cell line HepG2 Homo sapiens IC50 = 42657.95 nM PMID[28117202]
NPT81 Cell line A549 Homo sapiens IC50 n.a. n.a. n.a. PMID[28117202]
NPT28438 Unchecked Unchecked n.a. IC50 n.a. n.a. n.a. PMID[28117202]
NPT28597 Protein complex CDK2/Cyclin A2 Homo sapiens Inhibition n.a. n.a. % PMID[31238183]
NPT2528 Organism Rhopalosiphum padi Rhopalosiphum padi Activity = 10.0 % DOI[10.1016/j.indcrop.2012.09.012]
NPT2528 Organism Rhopalosiphum padi Rhopalosiphum padi Ratio = 0.8 n.a. DOI[10.1016/j.indcrop.2012.09.012]
NPT348 Organism Myzus persicae Myzus persicae Activity = 29.0 % DOI[10.1016/j.indcrop.2012.09.012]
NPT348 Organism Myzus persicae Myzus persicae Ratio = 0.4 n.a. DOI[10.1016/j.indcrop.2012.09.012]
NPT30122 Protein complex CDK9/cyclin T1 Homo sapiens Inhibition = 27.6 % PMID[31238183]

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 NPC600177 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
0.8163 Intermediate Similarity NPC131624
0.8 Intermediate Similarity NPC301323
0.75 Intermediate Similarity NPC188203
0.7308 Intermediate Similarity NPC274327
0.6852 Remote Similarity NPC201451
0.6852 Remote Similarity NPC231772
0.6727 Remote Similarity NPC222830
0.6545 Remote Similarity NPC176775
0.6429 Remote Similarity NPC142540
0.6364 Remote Similarity NPC52611
0.6364 Remote Similarity NPC156222
0.6364 Remote Similarity NPC29353
0.625 Remote Similarity NPC604462
0.614 Remote Similarity NPC603662
0.6034 Remote Similarity NPC146165
0.5965 Remote Similarity NPC184136
0.5965 Remote Similarity NPC57030
0.5965 Remote Similarity NPC145379
0.5893 Remote Similarity NPC602963
0.5833 Remote Similarity NPC610914
0.5789 Remote Similarity NPC306821
0.5789 Remote Similarity NPC275836
0.5763 Remote Similarity NPC183597
0.5667 Remote Similarity NPC52005
0.5636 Remote Similarity NPC40818
0.5614 Remote Similarity NPC245546
0.5439 Remote Similarity NPC129680
0.5424 Remote Similarity NPC22519
0.5424 Remote Similarity NPC176665
0.5424 Remote Similarity NPC266597
0.5424 Remote Similarity NPC604085
0.5424 Remote Similarity NPC610380
0.5417 Remote Similarity NPC472385
0.541 Remote Similarity NPC4455
0.541 Remote Similarity NPC196439
0.541 Remote Similarity NPC12200
0.541 Remote Similarity NPC223579
0.5362 Remote Similarity NPC150908
0.5342 Remote Similarity NPC198324
0.5286 Remote Similarity NPC303485
0.5254 Remote Similarity NPC71334
0.5254 Remote Similarity NPC127447
0.5246 Remote Similarity NPC253634
0.5211 Remote Similarity NPC14606
0.5211 Remote Similarity NPC186227
0.5167 Remote Similarity NPC59951
0.5167 Remote Similarity NPC241838
0.5167 Remote Similarity NPC234133
0.5167 Remote Similarity NPC231018
0.5167 Remote Similarity NPC483773
0.5167 Remote Similarity NPC601901
0.5161 Remote Similarity NPC195202
0.5161 Remote Similarity NPC2476
0.5161 Remote Similarity NPC610401
0.5139 Remote Similarity NPC121649
0.5135 Remote Similarity NPC101191
0.5088 Remote Similarity NPC604293
0.5085 Remote Similarity NPC293183
0.5082 Remote Similarity NPC50715
0.5082 Remote Similarity NPC256283
0.5079 Remote Similarity NPC183950
0.5075 Remote Similarity NPC470402
0.5068 Remote Similarity NPC18699
0.5068 Remote Similarity NPC601565
0.5067 Remote Similarity NPC210094

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC600177 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