Natural Product: NPC99773

Natural Product IDNPC99773
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 KKTYCZKXENFEJP-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 4309692
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0003467] Linear 1,3-diarylpropanoids
        • [CHEMONTID:0001630] Chalcones and dihydrochalcones
          • [CHEMONTID:0003472] 2'-Hydroxychalcones

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 KKTYCZKXENFEJP-UHFFFAOYSA-N
Standard InCHI InChI=1S/C18H18O5/c1-21-13-10-15(20)18(17(11-13)23-3)14(19)9-8-12-6-4-5-7-16(12)22-2/h4-11,20H,1-3H3
SMILES COc1cc(c(C(=O)C=Cc2ccccc2OC)c(c1)OC)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   314.12 Volume:   325.631
?
Van der Waals volume.
Dense:   0.965 LogP:   3.272
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.42
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.2
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   14.0
TPSA:   64.99
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   1.0 Rings:   2.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.654 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.107 Fsp3:   0.167
MCE-18:   13.0
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Accepted GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.718 Fluc inhibitor:   0.994
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.591
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.807
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.488 Promiscuous compounds:   0.434

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.868 MDCK Permeability:   -4.801
Pgp-inhibitor:   0.847 Pgp-substrate:   0.031
PAMPA:   0.003
?
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):   0.035
20% Bioavailability (F20%):   0.03 30% Bioavailability (F30%):   0.106
50% Bioavailability (F50%):   0.82

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.436 MRP1:   0.432
Plasma Protein Binding (PPB):   98.744% Volume Distribution (VD):   -0.037
Fu: 0.813%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.997
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.916
BSEP inhibitor:   0.904

ADMET: Metabolism

CYP1A2-inhibitor:   0.034 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.715 CYP2C19-substrate:   0.999
CYP2C9-inhibitor:   1.0 CYP2C9-substrate:   0.995
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   1.0
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.531
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.917
?
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):  7.001 Half-life (T1/2):  0.62

ADMET: Toxicity

hERG Blockers:  0.263 hERG Blockers (10um):  0.547
Human Hepatotoxicity (H-HT):  0.554 Drug-induced Liver Injury (DILI):  0.474
AMES Toxicity:  0.601 Rat Oral Acute Toxicity:  0.208
Maximum Recommended Daily Dose:  0.424 Skin Sensitization:  0.686
Carcinogencity:  0.373 Eye Corrosion:  0.023
Eye Irritation:  0.948 Respiratory Toxicity:  0.804
Drug-induced Neurotoxicity:  0.656 Ototoxicity:  0.307
Hematotoxicity:  0.276 Drug-induced Nephrotoxicity:  0.505
Genotoxicity:  0.099 RPMI-8226 Immunitoxicity:  0.147
A549 Cytotoxicity:  0.273 Hek293 Cytotoxicity:  0.42
BCF:   1.596
?
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:   4.143
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.353
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.805
?
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
NPO18156 Andrographis lineata Species Acanthaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18156 Andrographis lineata Species Acanthaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO18156 Andrographis lineata Species Acanthaceae 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 NPC99773 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
1.0 High Similarity NPC175098
0.7917 Intermediate Similarity NPC119663
0.7447 Intermediate Similarity NPC188646
0.7143 Intermediate Similarity NPC476333
0.7143 Intermediate Similarity NPC337373
0.6875 Remote Similarity NPC242294
0.68 Remote Similarity NPC472366
0.6731 Remote Similarity NPC472367
0.6731 Remote Similarity NPC472368
0.6667 Remote Similarity NPC473391
0.66 Remote Similarity NPC263670
0.6538 Remote Similarity NPC472364
0.6471 Remote Similarity NPC471417
0.6346 Remote Similarity NPC472365
0.5789 Remote Similarity NPC606423
0.56 Remote Similarity NPC212631
0.56 Remote Similarity NPC608685
0.537 Remote Similarity NPC87231
0.5333 Remote Similarity NPC305518
0.5094 Remote Similarity NPC64359
0.5091 Remote Similarity NPC92722
0.5091 Remote Similarity NPC56031

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC99773 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