Natural Product: NPC219945

Natural Product IDNPC219945
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 NXLOLUFNDSBYTP-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 10222
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0000259] Prenol lipids
        • [CHEMONTID:0001551] Diterpenoids

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 NXLOLUFNDSBYTP-UHFFFAOYSA-N
Standard InCHI InChI=1S/C18H18/c1-12(2)14-7-10-17-15(11-14)8-9-16-13(3)5-4-6-18(16)17/h4-12H,1-3H3
SMILES CC(C)c1ccc2c(ccc3c(C)cccc23)c1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   234.14 Volume:   275.76
?
Van der Waals volume.
Dense:   0.849 LogP:   6.028
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   4.627
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -6.522
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   16.0
TPSA:   0.0
?
Topological Polar Surface Area.
 H-Bond Acceptor:   0.0
H-Bond Donor:   0.0 Rings:   3.0
Heavy Atoms:   0.0

MedChem Properties

QED Drug-Likeness Score:   0.493 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   1.783 Fsp3:   0.222
MCE-18:   16.0
?
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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.853 Fluc inhibitor:   0.698
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.585
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.004
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.842 Promiscuous compounds:   0.122

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.392 MDCK Permeability:   -4.588
Pgp-inhibitor:   0.972 Pgp-substrate:   0.157
PAMPA:   0.01
?
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):   0.0
20% Bioavailability (F20%):   0.144 30% Bioavailability (F30%):   0.522
50% Bioavailability (F50%):   0.953

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.426 MRP1:   0.983
Plasma Protein Binding (PPB):   99.179% Volume Distribution (VD):   0.266
Fu: 0.382%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.986
OATP1B3 inhibitor:   0.981 BCRP inhibitor:   0.355
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.915 CYP1A2-substrate:   0.998
CYP2C19-inhibitor:   0.986 CYP2C19-substrate:   0.946
CYP2C9-inhibitor:   0.067 CYP2C9-substrate:   0.07
CYP2D6-inhibitor:   0.011 CYP2D6-substrate:   0.028
CYP3A4-inhibitor:   0.979 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.201 CYP2C8-inhibitor:   0.996
HLM stability:   0.998
?
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):  9.038 Half-life (T1/2):  0.483

ADMET: Toxicity

hERG Blockers:  0.267 hERG Blockers (10um):  0.683
Human Hepatotoxicity (H-HT):  0.717 Drug-induced Liver Injury (DILI):  0.855
AMES Toxicity:  0.735 Rat Oral Acute Toxicity:  0.55
Maximum Recommended Daily Dose:  0.683 Skin Sensitization:  0.489
Carcinogencity:  0.791 Eye Corrosion:  0.056
Eye Irritation:  0.96 Respiratory Toxicity:  0.837
Drug-induced Neurotoxicity:  0.856 Ototoxicity:  0.711
Hematotoxicity:  0.618 Drug-induced Nephrotoxicity:  0.848
Genotoxicity:  0.114 RPMI-8226 Immunitoxicity:  0.086
A549 Cytotoxicity:  0.349 Hek293 Cytotoxicity:  0.422
BCF:   3.352
?
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:   4.546
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.434
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.878
?
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
NPO12068 Firmiana simplex Species Malvaceae Eukaryota n.a. n.a. n.a. PMID[16124753]
NPO2669 Bowdichia virgilioides Species Fabaceae Eukaryota n.a. xylem n.a. PMID[16286304]
NPO2669 Bowdichia virgilioides Species Fabaceae Eukaryota Seeds n.a. n.a. PMID[29182338]
NPO8443 Uvaria microcarpa Species Annonaceae Eukaryota n.a. n.a. n.a. PMID[37531297]
NPO5752 Pholas dactylus Species Pholadidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4844 Acacia simplicifolia Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2669 Bowdichia virgilioides Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1406 Centaurea zuccariniana Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8962 Cousinia canescens Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12068 Firmiana simplex Species Malvaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8140 Nauclea parva Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5365 Tetradenia glauca Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9947 Teucrium scorodonia Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2905 Tinospora hainanensis Species Menispermaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21689 Titanotrichum oldhamii Species Gesneriaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8443 Uvaria microcarpa Species Annonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4037 Veronica anagallis Species Plantaginaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1255 Waitzia acuminata Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3463 Wrightia tinctoria Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO6937 Xylaria hypoxylon Species Xylariaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8770 Euphorbia wallichii Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12068 Firmiana simplex Species Malvaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO8770 Euphorbia wallichii Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO2905 Tinospora hainanensis Species Menispermaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO2905 Tinospora hainanensis Species Menispermaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO9947 Teucrium scorodonia Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO8770 Euphorbia wallichii Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO12068 Firmiana simplex Species Malvaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO12068 Firmiana simplex Species Malvaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO4844 Acacia simplicifolia Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9947 Teucrium scorodonia Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21689 Titanotrichum oldhamii Species Gesneriaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8770 Euphorbia wallichii Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4037 Veronica anagallis Species Plantaginaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2905 Tinospora hainanensis Species Menispermaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3463 Wrightia tinctoria Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12068 Firmiana simplex Species Malvaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5752 Pholas dactylus Species Pholadidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8962 Cousinia canescens Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1255 Waitzia acuminata Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2669 Bowdichia virgilioides Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8443 Uvaria microcarpa Species Annonaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8140 Nauclea parva Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5365 Tetradenia glauca Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6937 Xylaria hypoxylon Species Xylariaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1406 Centaurea zuccariniana Species Asteraceae 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 NPC219945 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
NPC

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC219945 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