Natural Product: NPC34555

Natural Product IDNPC34555
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 JFINBCWMRIJTDN-NLDJYOPPSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 11565893
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0000259] Prenol lipids
        • [CHEMONTID:0001283] Terpene lactones
          • [CHEMONTID:0001538] Diterpene lactones

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 JFINBCWMRIJTDN-NLDJYOPPSA-N
Standard InCHI InChI=1S/C20H26O3/c1-11-13-9-12-5-6-16-19(2,3)17(21)7-8-20(16,4)14(12)10-15(13)23-18(11)22/h9,14-16H,5-8,10H2,1-4H3/t14-,15-,16-,20+/m1/s1
SMILES CC1=C2C=C3CC[C@@H]4C(C)(C)C(=O)CC[C@@]4(C)[C@@H]3C[C@H]2OC1=O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   314.19 Volume:   336.075
?
Van der Waals volume.
Dense:   0.935 LogP:   2.203
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.605
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.722
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   0.0 Rigid Bonds:   22.0
TPSA:   43.37
?
Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   0.0 Rings:   4.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.635 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.484 Fsp3:   0.7
MCE-18:   67.294
?
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:   0.375 Fluc inhibitor:   0.008
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.121
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.002
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.618 Promiscuous compounds:   0.391

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.722 MDCK Permeability:   -4.549
Pgp-inhibitor:   0.764 Pgp-substrate:   0.15
PAMPA:   0.766
?
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%):   0.064 30% Bioavailability (F30%):   0.175
50% Bioavailability (F50%):   0.53

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.147 MRP1:   0.994
Plasma Protein Binding (PPB):   97.637% Volume Distribution (VD):   0.162
Fu: 2.673%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.993
OATP1B3 inhibitor:   0.983 BCRP inhibitor:   0.026
BSEP inhibitor:   0.992

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.002
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.789 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.017
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   0.928
CYP2B6-substrate:   0.59 CYP2C8-inhibitor:   0.965
HLM stability:   0.941
?
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):  7.786 Half-life (T1/2):  0.788

ADMET: Toxicity

hERG Blockers:  0.029 hERG Blockers (10um):  0.164
Human Hepatotoxicity (H-HT):  0.72 Drug-induced Liver Injury (DILI):  0.809
AMES Toxicity:  0.54 Rat Oral Acute Toxicity:  0.346
Maximum Recommended Daily Dose:  0.682 Skin Sensitization:  0.96
Carcinogencity:  0.867 Eye Corrosion:  0.231
Eye Irritation:  0.733 Respiratory Toxicity:  0.45
Drug-induced Neurotoxicity:  0.687 Ototoxicity:  0.403
Hematotoxicity:  0.698 Drug-induced Nephrotoxicity:  0.919
Genotoxicity:  0.943 RPMI-8226 Immunitoxicity:  0.102
A549 Cytotoxicity:  0.149 Hek293 Cytotoxicity:  0.151
BCF:   0.77
?
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:   3.511
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.96
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.391
?
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
NPO26629 Caesalpinia pulcherrima Species Fabaceae Eukaryota n.a. stem n.a. DOI[10.1021/np0201523]
NPO26629 Caesalpinia pulcherrima Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[12193012]
NPO26661 Heimia salicifolia Species Lythraceae Eukaryota n.a. n.a. n.a. PMID[19299148]
NPO25837 Euphorbia micractina Species Euphorbiaceae Eukaryota Roots Zhang County, Gansu Province, China 2002-Sep PMID[19702283]
NPO25837 Euphorbia micractina Species Euphorbiaceae Eukaryota n.a. root n.a. PMID[21534583]
NPO25837 Euphorbia micractina Species Euphorbiaceae Eukaryota Roots n.a. n.a. PMID[23691978]
NPO40127 Euphorbia soongarica Species Euphorbiaceae Eukaryota n.a. n.a. n.a. PMID[28590124]
NPO40126 Euphorbia pedroi Species Euphorbiaceae Eukaryota n.a. n.a. n.a. PMID[30199257]
NPO26629 Caesalpinia pulcherrima Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[3783154]
NPO21065 Euphorbia calyptrata Species Euphorbiaceae Eukaryota n.a. n.a. n.a. PMID[38528316]
NPO26190 Aspergillus wentii Species Aspergillaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18641 Radix euphorbiae pekinensis Species Lymnaeidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25837 Euphorbia micractina Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO40127 Euphorbia soongarica Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26629 Caesalpinia pulcherrima Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5402 Hypogymnia billardieri Species Parmeliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26661 Heimia salicifolia Species Lythraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26839 Microlepia speluncae Species Dennstaedtiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8770 Euphorbia wallichii Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16779.1 Amaranthus hybridus subsp. cruentus Subspecies Amaranthaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12190 Carduus acanthoides Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1891 Chorilaena quercifolia Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8081 Crataegus flava Species Rosaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8770 Euphorbia wallichii Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO1775 Euphorbia pekinensis Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO26629 Caesalpinia pulcherrima Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO1775 Euphorbia pekinensis Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO8770 Euphorbia wallichii Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO18641 Radix euphorbiae pekinensis Species Lymnaeidae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO26629 Caesalpinia pulcherrima Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO26172 Dryopteris sacrosancta Species Dryopteridaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO1775 Euphorbia pekinensis Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO12190 Carduus acanthoides Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO1775 Euphorbia pekinensis Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO4283 Tripteris vaillantii Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21665.1 Mycobacterium avium subsp. paratuberculosis Subspecies Mycobacteriaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO1891 Chorilaena quercifolia Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21065 Euphorbia calyptrata Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26215 Eleusine indica Species Poaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26190 Aspergillus wentii Species Aspergillaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26172 Dryopteris sacrosancta Species Dryopteridaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8081 Crataegus flava Species Rosaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26888 Narcissus asturiensis Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26383 Lemna trisulca Species Araceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8770 Euphorbia wallichii Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26433 Conus marmoreus Species Conidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26906 Astragalus interpositus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21295 Botryotrichum piluliferum Species Chaetomiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26839 Microlepia speluncae Species Dennstaedtiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26931 Dolichothele uberiformis n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO16779.1 Amaranthus hybridus subsp. cruentus Subspecies Amaranthaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5402 Hypogymnia billardieri Species Parmeliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12190 Carduus acanthoides Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26629 Caesalpinia pulcherrima Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1775 Euphorbia pekinensis Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29041 Scutellaria orientalis Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25837 Euphorbia micractina Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25876 Chromodoris inornata Species Chromodorididae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26568 Rubus koehneanus Species Rosaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26661 Heimia salicifolia Species Lythraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26411 Stemphylium radicinum Species Pleosporaceae 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
NPT668 Individual protein P-glycoprotein 1 Homo sapiens Ratio = 1.84 n.a. PMID[30199257]
NPT668 Individual protein P-glycoprotein 1 Homo sapiens Ratio = 10.23 n.a. PMID[30199257]
NPT668 Individual protein P-glycoprotein 1 Homo sapiens Ratio = 0.44 n.a. PMID[30199257]
NPT668 Individual protein P-glycoprotein 1 Homo sapiens Ratio = 0.98 n.a. PMID[30199257]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT91 Cell line KB Homo sapiens IC50 = 22440.0 nM PMID[28590124]
NPT886 Cell line NIH3T3 Mus musculus IC50 > 10000.0 nM PMID[30199257]
NPT407 Cell line COLO 205 Homo sapiens IC50 > 10000.0 nM PMID[30199257]
NPT2641 Cell line COLO 320 Homo sapiens IC50 > 10000.0 nM PMID[30199257]
NPT1864 Cell line L5178Y Mus musculus IC50 > 10000.0 nM PMID[30199257]
NPT171 Cell line MRC5 Homo sapiens IC50 > 10000.0 nM PMID[30199257]
NPT2 Others Unspecified n.a. IC50 > 30000.0 nM PMID[28590124]
NPT2 Others Unspecified n.a. Ratio = 0.45 n.a. PMID[28590124]

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 NPC34555 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
0.7778 Intermediate Similarity NPC482370
0.75 Intermediate Similarity NPC482371
0.7 Intermediate Similarity NPC482372
0.6607 Remote Similarity NPC221111
0.6607 Remote Similarity NPC280149
0.6176 Remote Similarity NPC482373
0.6102 Remote Similarity NPC31361
0.6034 Remote Similarity NPC606478
0.5965 Remote Similarity NPC479258
0.5932 Remote Similarity NPC479261
0.5932 Remote Similarity NPC611260
0.5915 Remote Similarity NPC482374
0.5915 Remote Similarity NPC482375
0.5833 Remote Similarity NPC296152
0.5789 Remote Similarity NPC611362
0.5484 Remote Similarity NPC479259
0.5345 Remote Similarity NPC609118
0.5323 Remote Similarity NPC156266
0.5312 Remote Similarity NPC478674

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC34555 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