Natural Product: NPC186436

Natural Product IDNPC186436
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 QZJVBGCZOLNWHW-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 321347
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0002585] O-methylated flavonoids
          • [CHEMONTID:0002592] 7-O-methylated flavonoids

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 QZJVBGCZOLNWHW-UHFFFAOYSA-N
Standard InCHI InChI=1S/C17H16O6/c1-21-10-6-12(19)17-13(20)8-14(23-16(17)7-10)9-3-4-11(18)15(5-9)22-2/h3-7,14,18-19H,8H2,1-2H3
SMILES COc1cc(c2C(=O)CC(c3ccc(c(c3)OC)O)Oc2c1)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   316.09 Volume:   311.205
?
Van der Waals volume.
Dense:   1.016 LogP:   2.746
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.868
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.38
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   18.0
TPSA:   85.22
?
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:   0.905 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.811 Fsp3:   0.235
MCE-18:   57.429
?
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:   1
Chelating Alert:   1 PAINS Alert:   0
Colloidal aggregators:   0.418 Fluc inhibitor:   0.401
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.337
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.396
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.321 Promiscuous compounds:   0.032

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.049 MDCK Permeability:   -4.773
Pgp-inhibitor:   0.985 Pgp-substrate:   0.017
PAMPA:   0.017
?
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):   0.033
20% Bioavailability (F20%):   0.006 30% Bioavailability (F30%):   0.451
50% Bioavailability (F50%):   0.996

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.001 MRP1:   0.739
Plasma Protein Binding (PPB):   95.947% Volume Distribution (VD):   -0.123
Fu: 3.825%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.999
BSEP inhibitor:   0.982

ADMET: Metabolism

CYP1A2-inhibitor:   0.999 CYP1A2-substrate:   0.99
CYP2C19-inhibitor:   0.948 CYP2C19-substrate:   0.967
CYP2C9-inhibitor:   0.999 CYP2C9-substrate:   0.001
CYP2D6-inhibitor:   0.66 CYP2D6-substrate:   0.996
CYP3A4-inhibitor:   0.021 CYP3A4-substrate:   0.224
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.819
HLM stability:   0.954
?
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):  6.419 Half-life (T1/2):  1.243

ADMET: Toxicity

hERG Blockers:  0.119 hERG Blockers (10um):  0.538
Human Hepatotoxicity (H-HT):  0.59 Drug-induced Liver Injury (DILI):  0.702
AMES Toxicity:  0.73 Rat Oral Acute Toxicity:  0.535
Maximum Recommended Daily Dose:  0.526 Skin Sensitization:  0.524
Carcinogencity:  0.687 Eye Corrosion:  0.013
Eye Irritation:  0.963 Respiratory Toxicity:  0.825
Drug-induced Neurotoxicity:  0.353 Ototoxicity:  0.366
Hematotoxicity:  0.362 Drug-induced Nephrotoxicity:  0.56
Genotoxicity:  0.741 RPMI-8226 Immunitoxicity:  0.163
A549 Cytotoxicity:  0.438 Hek293 Cytotoxicity:  0.58
BCF:   1.141
?
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:   3.605
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.5
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.776
?
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
NPO29463 Pogostemon cablin Species Lamiaceae Eukaryota n.a. leaf n.a. PMID[12575075]
NPO29463 Pogostemon cablin Species Lamiaceae Eukaryota n.a. stem n.a. PMID[12575075]
NPO29463 Pogostemon cablin Species Lamiaceae Eukaryota n.a. whole plant n.a. PMID[15577255]
NPO29463 Pogostemon cablin Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[30188125]
NPO29463 Pogostemon cablin Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29463 Pogostemon cablin Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO29463 Pogostemon cablin Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO29463 Pogostemon cablin Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO29463 Pogostemon cablin Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO29463 Pogostemon cablin Species Lamiaceae 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

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 NPC186436 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
0.7679 Intermediate Similarity NPC477840
0.7647 Intermediate Similarity NPC329203
0.7647 Intermediate Similarity NPC222342
0.7593 Intermediate Similarity NPC236637
0.7358 Intermediate Similarity NPC18727
0.7358 Intermediate Similarity NPC599987
0.7255 Intermediate Similarity NPC6407
0.7255 Intermediate Similarity NPC545184
0.7115 Intermediate Similarity NPC150648
0.7091 Intermediate Similarity NPC474836
0.6866 Remote Similarity NPC236934
0.6852 Remote Similarity NPC486095
0.6667 Remote Similarity NPC73028
0.6538 Remote Similarity NPC140890
0.6429 Remote Similarity NPC310135
0.625 Remote Similarity NPC35038
0.5862 Remote Similarity NPC112246
0.575 Remote Similarity NPC261254
0.5625 Remote Similarity NPC480158
0.5556 Remote Similarity NPC195796
0.5556 Remote Similarity NPC488550
0.5556 Remote Similarity NPC477841
0.5517 Remote Similarity NPC274784
0.5517 Remote Similarity NPC20709
0.55 Remote Similarity NPC302950
0.5479 Remote Similarity NPC472624
0.5479 Remote Similarity NPC27337
0.5479 Remote Similarity NPC472598
0.5479 Remote Similarity NPC602605
0.5439 Remote Similarity NPC32441
0.5439 Remote Similarity NPC79943
0.5424 Remote Similarity NPC475267
0.5424 Remote Similarity NPC606248
0.5412 Remote Similarity NPC241196
0.5405 Remote Similarity NPC472632
0.5345 Remote Similarity NPC484336
0.5345 Remote Similarity NPC484337
0.5333 Remote Similarity NPC158188
0.5333 Remote Similarity NPC474055
0.5333 Remote Similarity NPC469758
0.5333 Remote Similarity NPC48208
0.5333 Remote Similarity NPC601395
0.5263 Remote Similarity NPC472634
0.5254 Remote Similarity NPC99597
0.5254 Remote Similarity NPC480993
0.5254 Remote Similarity NPC338131
0.5246 Remote Similarity NPC27139
0.5211 Remote Similarity NPC219163
0.5211 Remote Similarity NPC39351
0.5167 Remote Similarity NPC321011
0.5167 Remote Similarity NPC294852
0.5167 Remote Similarity NPC102904
0.5167 Remote Similarity NPC469764
0.5167 Remote Similarity NPC103976
0.5167 Remote Similarity NPC210084
0.5167 Remote Similarity NPC188679
0.5128 Remote Similarity NPC472635
0.5082 Remote Similarity NPC602118
0.5068 Remote Similarity NPC29830

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC186436 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
0.55 Remote Similarity NPD1934 Phase 0
0.5439 Remote Similarity NPD1552 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