Natural Product: NPC138291

Natural Product IDNPC138291
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 BTVSNVKVWQGSKK-ZDUSSCGKSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 12098358
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0002585] O-methylated flavonoids
          • [CHEMONTID:0002593] 8-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 BTVSNVKVWQGSKK-ZDUSSCGKSA-N
Standard InCHI InChI=1S/C17H16O6/c1-21-14-8-12(20)15-11(19)7-13(23-17(15)16(14)22-2)9-5-3-4-6-10(9)18/h3-6,8,13,18,20H,7H2,1-2H3/t13-/m0/s1
SMILES COc1cc(c2C(=O)C[C@@H](c3ccccc3O)Oc2c1OC)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   316.09 Volume:   311.205
?
Van der Waals volume.
Dense:   1.016 LogP:   2.719
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.859
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.066
?
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:   2.929 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:   0 PAINS Alert:   0
Colloidal aggregators:   0.316 Fluc inhibitor:   0.694
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.303
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.362
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.276 Promiscuous compounds:   0.07

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.972 MDCK Permeability:   -4.767
Pgp-inhibitor:   0.437 Pgp-substrate:   0.038
PAMPA:   0.121
?
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):   0.003
20% Bioavailability (F20%):   0.07 30% Bioavailability (F30%):   0.098
50% Bioavailability (F50%):   0.729

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.348 MRP1:   0.953
Plasma Protein Binding (PPB):   95.029% Volume Distribution (VD):   -0.116
Fu: 4.589%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.841
OATP1B3 inhibitor:   0.967 BCRP inhibitor:   0.622
BSEP inhibitor:   0.966

ADMET: Metabolism

CYP1A2-inhibitor:   0.725 CYP1A2-substrate:   0.928
CYP2C19-inhibitor:   0.001 CYP2C19-substrate:   0.949
CYP2C9-inhibitor:   0.007 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.009 CYP2D6-substrate:   0.098
CYP3A4-inhibitor:   0.984 CYP3A4-substrate:   0.973
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.016
HLM stability:   0.946
?
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):  5.473 Half-life (T1/2):  1.22

ADMET: Toxicity

hERG Blockers:  0.068 hERG Blockers (10um):  0.434
Human Hepatotoxicity (H-HT):  0.797 Drug-induced Liver Injury (DILI):  0.581
AMES Toxicity:  0.652 Rat Oral Acute Toxicity:  0.716
Maximum Recommended Daily Dose:  0.657 Skin Sensitization:  0.864
Carcinogencity:  0.324 Eye Corrosion:  0.05
Eye Irritation:  0.973 Respiratory Toxicity:  0.912
Drug-induced Neurotoxicity:  0.734 Ototoxicity:  0.373
Hematotoxicity:  0.191 Drug-induced Nephrotoxicity:  0.782
Genotoxicity:  0.897 RPMI-8226 Immunitoxicity:  0.239
A549 Cytotoxicity:  0.751 Hek293 Cytotoxicity:  0.45
BCF:   1.148
?
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:   3.593
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.203
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.189
?
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
NPO3578 Andrographis paniculata Species Acanthaceae Eukaryota n.a. n.a. n.a. DOI[10.1111/ppl.12252]
NPO3578 Andrographis paniculata Species Acanthaceae Eukaryota n.a. root n.a. PMID[15894448]
NPO3578 Andrographis paniculata Species Acanthaceae Eukaryota n.a. leaf n.a. PMID[15894448]
NPO3578 Andrographis paniculata Species Acanthaceae Eukaryota aerial parts purchased in Juhuacun herbal market, Kunming, Yunnan Province, China 2002-Oct PMID[16562826]
NPO3578 Andrographis paniculata Species Acanthaceae Eukaryota n.a. n.a. n.a. PMID[18357994]
NPO3578 Andrographis paniculata Species Acanthaceae Eukaryota n.a. leaf n.a. PMID[21598983]
NPO3578 Andrographis paniculata Species Acanthaceae Eukaryota n.a. leaf n.a. PMID[22026410]
NPO3578 Andrographis paniculata Species Acanthaceae Eukaryota n.a. n.a. n.a. PMID[8377022]
NPO18156 Andrographis lineata Species Acanthaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3578 Andrographis paniculata Species Acanthaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3578 Andrographis paniculata Species Acanthaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO18156 Andrographis lineata Species Acanthaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO3578 Andrographis paniculata Species Acanthaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO3578 Andrographis paniculata Species Acanthaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO3578 Andrographis paniculata Species Acanthaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO3578 Andrographis paniculata Species Acanthaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
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 NPC138291 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
0.7551 Intermediate Similarity NPC37392
0.6415 Remote Similarity NPC107586
0.6143 Remote Similarity NPC472384
0.5926 Remote Similarity NPC4743
0.5714 Remote Similarity NPC324134
0.5714 Remote Similarity NPC40833
0.5345 Remote Similarity NPC310135
0.5263 Remote Similarity NPC194432
0.5192 Remote Similarity NPC472917
0.5179 Remote Similarity NPC295261
0.5179 Remote Similarity NPC296490
0.5161 Remote Similarity NPC109183
0.5161 Remote Similarity NPC306829
0.5139 Remote Similarity NPC472381
0.5088 Remote Similarity NPC150648
0.5077 Remote Similarity NPC20488
0.5068 Remote Similarity NPC472380

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC138291 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