Natural Product: NPC83421

Natural Product IDNPC83421
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 FOINLJRVEBYARJ-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 328236
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000145] Coumarins and derivatives
        • [CHEMONTID:0000358] Furanocoumarins
          • [CHEMONTID:0002569] Linear furanocoumarins
            • [CHEMONTID:0000202] Psoralens

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 FOINLJRVEBYARJ-UHFFFAOYSA-N
Standard InCHI InChI=1S/C16H16O6/c1-16(2,19)11(17)8-21-15-13-10(5-6-20-13)7-9-3-4-12(18)22-14(9)15/h3-7,11,17,19H,8H2,1-2H3
SMILES CC(C)(C(COc1c2c(cco2)cc2ccc(=O)oc12)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   304.09 Volume:   296.545
?
Van der Waals volume.
Dense:   1.025 LogP:   0.886
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.275
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.374
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   16.0
TPSA:   93.04
?
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:   0.717 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.335 Fsp3:   0.312
MCE-18:   38.0
?
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:   0 PAINS Alert:   0
Colloidal aggregators:   0.323 Fluc inhibitor:   0.158
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.978
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.139
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.087 Promiscuous compounds:   0.212

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.468 MDCK Permeability:   -4.576
Pgp-inhibitor:   0.0 Pgp-substrate:   0.0
PAMPA:   0.84
?
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):   0.001
20% Bioavailability (F20%):   0.314 30% Bioavailability (F30%):   0.277
50% Bioavailability (F50%):   0.183

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.002 MRP1:   0.994
Plasma Protein Binding (PPB):   71.032% Volume Distribution (VD):   -0.107
Fu: 26.274%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.993
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.0
BSEP inhibitor:   0.522

ADMET: Metabolism

CYP1A2-inhibitor:   0.019 CYP1A2-substrate:   0.988
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.003
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   1.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   1.0
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.0
?
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):  10.182 Half-life (T1/2):  1.006

ADMET: Toxicity

hERG Blockers:  0.118 hERG Blockers (10um):  0.296
Human Hepatotoxicity (H-HT):  0.572 Drug-induced Liver Injury (DILI):  0.559
AMES Toxicity:  0.507 Rat Oral Acute Toxicity:  0.267
Maximum Recommended Daily Dose:  0.749 Skin Sensitization:  0.095
Carcinogencity:  0.777 Eye Corrosion:  0.001
Eye Irritation:  0.566 Respiratory Toxicity:  0.374
Drug-induced Neurotoxicity:  0.117 Ototoxicity:  0.608
Hematotoxicity:  0.228 Drug-induced Nephrotoxicity:  0.268
Genotoxicity:  0.98 RPMI-8226 Immunitoxicity:  0.037
A549 Cytotoxicity:  0.047 Hek293 Cytotoxicity:  0.259
BCF:   0.486
?
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:   3.128
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.598
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.938
?
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
NPO24758 Angelica dahurica Species Apiaceae Eukaryota n.a. root n.a. DOI[10.5012/bkcs.2003.24.11.1699]
NPO5954 Petroselinum crispum Species Apiaceae Eukaryota n.a. callus n.a. PMID[10552648]
NPO24758 Angelica dahurica Species Apiaceae Eukaryota n.a. root n.a. PMID[12510838]
NPO3364 Murraya koenigii Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[12662104]
NPO24758 Angelica dahurica Species Apiaceae Eukaryota n.a. root n.a. PMID[15646793]
NPO31471 Poncirus trifoliata Species Rutaceae Eukaryota n.a. fruit n.a. PMID[17666859]
NPO5954 Petroselinum crispum Species Apiaceae Eukaryota n.a. leaf n.a. PMID[18214349]
NPO5954 Petroselinum crispum Species Apiaceae Eukaryota n.a. seed n.a. PMID[21049975]
NPO24758 Angelica dahurica Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[21625478]
NPO24758 Angelica dahurica Species Apiaceae Eukaryota n.a. root n.a. PMID[21657081]
NPO5954 Petroselinum crispum Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[21800857]
NPO3364 Murraya koenigii Species Rutaceae Eukaryota n.a. Sri Lankan n.a. PMID[23376010]
NPO3364 Murraya koenigii Species Rutaceae Eukaryota fruits Coimbatore, India 2010-JUN PMID[23691929]
NPO21771 Citrus trifoliata Species Rutaceae Eukaryota n.a. fruit n.a. PMID[23872723]
NPO3364 Murraya koenigii Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[27136692]
NPO24758 Angelica dahurica Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[27444348]
NPO40718 Indian beech tree Strain n.a. n.a. n.a. n.a. n.a. PMID[30108931]
NPO24758 Angelica dahurica Species Apiaceae Eukaryota Roots n.a. n.a. PMID[31464439]
NPO21771 Citrus trifoliata Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[32996318]
NPO5954 Petroselinum crispum Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[36840093]
NPO5954 Petroselinum crispum Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[38719900]
NPO3364 Murraya koenigii Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[39414752]
NPO40718 Indian beech tree Strain n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO3364 Murraya koenigii Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21771 Citrus trifoliata Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5954 Petroselinum crispum Species Apiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO31471 Poncirus trifoliata Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24771 Boenninghausenia albiflora Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12746 Pleurospermum rivulorum Species Apiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5954 Petroselinum crispum Species Apiaceae Eukaryota n.a. n.a. Database[FooDB]
NPO5954 Petroselinum crispum Species Apiaceae Eukaryota Shoot n.a. n.a. Database[FooDB]
NPO5954 Petroselinum crispum Species Apiaceae Eukaryota Seed n.a. n.a. Database[FooDB]
NPO5954 Petroselinum crispum Species Apiaceae Eukaryota Root n.a. n.a. Database[FooDB]
NPO5954 Petroselinum crispum Species Apiaceae Eukaryota Plant n.a. n.a. Database[FooDB]
NPO5954 Petroselinum crispum Species Apiaceae Eukaryota Leaf n.a. n.a. Database[FooDB]
NPO5954 Petroselinum crispum Species Apiaceae Eukaryota Fruit n.a. n.a. Database[FooDB]
NPO5954 Petroselinum crispum Species Apiaceae Eukaryota n.a. n.a. Database[FooDB]
NPO5954 Petroselinum crispum Species Apiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO24758 Angelica dahurica Species Apiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO31471 Poncirus trifoliata Species Rutaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO24771 Boenninghausenia albiflora Species Rutaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO3364 Murraya koenigii Species Rutaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO12746 Pleurospermum rivulorum Species Apiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO5954 Petroselinum crispum Species Apiaceae Eukaryota n.a. n.a. Database[Phenol-Explorer]
NPO24771 Boenninghausenia albiflora Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO24758 Angelica dahurica Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO21771 Citrus trifoliata Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO5954 Petroselinum crispum Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO12746 Pleurospermum rivulorum Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO3364 Murraya koenigii Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO24771 Boenninghausenia albiflora Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO24758 Angelica dahurica Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO3364 Murraya koenigii Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO31471 Poncirus trifoliata Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO5954 Petroselinum crispum Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO21771 Citrus trifoliata Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO24758 Angelica dahurica Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO24758 Angelica dahurica Species Apiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3364 Murraya koenigii Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5954 Petroselinum crispum Species Apiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21771 Citrus trifoliata Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24771 Boenninghausenia albiflora Species Rutaceae 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
NPO5954 Petroselinum crispum Raw Seed 0.37 0.37 0.37 mg/100g Database [DUKE]

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
NPT1603 Individual protein Cytochrome P450 1A1 Homo sapiens Inhibition = 72.0 % PMID[30108931]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT1114 Organism Human immunodeficiency virus Human immunodeficiency virus EC50 = 0.115 ug.mL-1 PMID[27484512]

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 NPC83421 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 NPC51404
0.8113 Intermediate Similarity NPC215722
0.7959 Intermediate Similarity NPC487850
0.7143 Intermediate Similarity NPC173149
0.7143 Intermediate Similarity NPC179015
0.6964 Remote Similarity NPC243509
0.6863 Remote Similarity NPC33320
0.6842 Remote Similarity NPC602724
0.678 Remote Similarity NPC224165
0.6154 Remote Similarity NPC478570
0.6 Remote Similarity NPC216092
0.5909 Remote Similarity NPC478569
0.5634 Remote Similarity NPC478632
0.5556 Remote Similarity NPC478631
0.5469 Remote Similarity NPC107244
0.5455 Remote Similarity NPC198876
0.541 Remote Similarity NPC479800
0.5397 Remote Similarity NPC303210
0.5397 Remote Similarity NPC95472
0.5397 Remote Similarity NPC239270

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC83421 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
0.6863 Remote Similarity NPD919 Phase 4

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