Natural Product: NPC68620

Natural Product IDNPC68620
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 KLAGFFXRUOBTMA-DOEMEAPXSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 101675261
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 KLAGFFXRUOBTMA-DOEMEAPXSA-N
Standard InCHI InChI=1S/C20H30O3/c1-14(10-13-21)6-8-16-15(2)7-9-17-19(16,3)11-5-12-20(17,4)18(22)23/h10,13,16-17H,2,5-9,11-12H2,1,3-4H3,(H,22,23)/b14-10+/t16-,17+,19+,20-/m0/s1
SMILES C/C(=CC=O)/CC[C@H]1C(=C)CC[C@@H]2[C@]1(C)CCC[C@]2(C)C(=O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   318.22 Volume:   353.188
?
Van der Waals volume.
Dense:   0.901 LogP:   3.574
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.886
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.98
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   15.0
TPSA:   54.37
?
Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   1.0 Rings:   2.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.451 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.225 Fsp3:   0.7
MCE-18:   43.0
?
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:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.137 Fluc inhibitor:   0.001
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.004
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.008
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.943 Promiscuous compounds:   0.095

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.078 MDCK Permeability:   -4.905
Pgp-inhibitor:   0.062 Pgp-substrate:   0.0
PAMPA:   0.448
?
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%):   0.01 30% Bioavailability (F30%):   0.004
50% Bioavailability (F50%):   0.095

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.004 MRP1:   0.946
Plasma Protein Binding (PPB):   97.366% Volume Distribution (VD):   -0.334
Fu: 3.261%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   0.997 BCRP inhibitor:   0.0
BSEP inhibitor:   0.984

ADMET: Metabolism

CYP1A2-inhibitor:   0.453 CYP1A2-substrate:   0.001
CYP2C19-inhibitor:   0.301 CYP2C19-substrate:   0.002
CYP2C9-inhibitor:   0.963 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.966 CYP3A4-substrate:   0.172
CYP2B6-substrate:   0.176 CYP2C8-inhibitor:   0.081
HLM stability:   0.055
?
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):  2.332 Half-life (T1/2):  1.179

ADMET: Toxicity

hERG Blockers:  0.029 hERG Blockers (10um):  0.122
Human Hepatotoxicity (H-HT):  0.684 Drug-induced Liver Injury (DILI):  0.295
AMES Toxicity:  0.26 Rat Oral Acute Toxicity:  0.499
Maximum Recommended Daily Dose:  0.481 Skin Sensitization:  0.964
Carcinogencity:  0.829 Eye Corrosion:  0.446
Eye Irritation:  0.94 Respiratory Toxicity:  0.743
Drug-induced Neurotoxicity:  0.513 Ototoxicity:  0.343
Hematotoxicity:  0.28 Drug-induced Nephrotoxicity:  0.84
Genotoxicity:  0.767 RPMI-8226 Immunitoxicity:  0.036
A549 Cytotoxicity:  0.015 Hek293 Cytotoxicity:  0.124
BCF:   1.318
?
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:   4.377
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.791
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.132
?
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
NPO13135 Campylotropis hirtella Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[19481938]
NPO12796 Periploca sepium Species Apocynaceae Eukaryota n.a. n.a. n.a. PMID[28294615]
NPO865 Dendrobium loddigesii Species Orchidaceae Eukaryota n.a. n.a. n.a. PMID[31291099]
NPO12205 Eucalyptus apodophylla Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1257 Distephanus angulifolius Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10922 Pentaclethra macrophylla Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7773 Crinum moorei Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9704 Sonneratia caseolaris Species Lythraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12796 Periploca sepium Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9319 Pterocaulon virgatum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO865 Dendrobium loddigesii Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7773 Crinum moorei Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO12796 Periploca sepium Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO6731 Ononis spinosa Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO865 Dendrobium loddigesii Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO13135 Campylotropis hirtella Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO12796 Periploca sepium Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO6731 Ononis spinosa Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO13135 Campylotropis hirtella Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO7773 Crinum moorei Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO865 Dendrobium loddigesii Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO865 Dendrobium loddigesii Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO12796 Periploca sepium Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO6731 Ononis spinosa Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO12796 Periploca sepium Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO865 Dendrobium loddigesii Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO11576 Glycosmis macrophylla Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22691 Mentha cardiaca Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6289 Ceropegia dichotoma Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9704 Sonneratia caseolaris Species Lythraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23384 Rhodiola semenovii Species Crassulaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO865 Dendrobium loddigesii Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10638 Plectranthus myrianthus Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3873 Crotalaria candicans Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11843 Stephania zippeliana Species Menispermaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12565 Hypericum polyanthemum Species Hypericaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11190 Veronica polita Species Plantaginaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10922 Pentaclethra macrophylla Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5043 Eria japonica Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8934 Gypsophila perfoliata Species Caryophyllaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9532 Vernonia cistifolia Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13135 Campylotropis hirtella Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10605 Tristania conferta Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5456 Juniperus drupacea Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7773 Crinum moorei Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1257 Distephanus angulifolius Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12796 Periploca sepium Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9319 Pterocaulon virgatum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21720 Talaromyces variabilis Species Trichocomaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7822.1 Eucalyptus globulus subsp. bicostata Subspecies Myrtaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12091 Martensia denticulata Species Delesseriaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO526 Salvia sessei Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6731 Ononis spinosa Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12205 Eucalyptus apodophylla Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1815 Breonia chinensis Species Rubiaceae 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 NPC68620 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
0.7917 Intermediate Similarity NPC481630
0.7692 Intermediate Similarity NPC40228
0.7647 Intermediate Similarity NPC239098
0.74 Intermediate Similarity NPC72343
0.7273 Intermediate Similarity NPC14203
0.7273 Intermediate Similarity NPC229584
0.7255 Intermediate Similarity NPC59436
0.72 Intermediate Similarity NPC488498
0.72 Intermediate Similarity NPC61952
0.72 Intermediate Similarity NPC603184
0.6909 Remote Similarity NPC600691
0.6792 Remote Similarity NPC18819
0.6792 Remote Similarity NPC46610
0.6731 Remote Similarity NPC198240
0.6731 Remote Similarity NPC237591
0.6731 Remote Similarity NPC36616
0.6731 Remote Similarity NPC3753
0.6667 Remote Similarity NPC477782
0.6552 Remote Similarity NPC477783
0.6481 Remote Similarity NPC471159
0.6481 Remote Similarity NPC123880
0.6481 Remote Similarity NPC91369
0.6364 Remote Similarity NPC269543
0.6364 Remote Similarity NPC247783
0.6316 Remote Similarity NPC232344
0.6226 Remote Similarity NPC99154
0.5818 Remote Similarity NPC161923
0.5818 Remote Similarity NPC183503
0.5818 Remote Similarity NPC283908
0.5818 Remote Similarity NPC103958
0.5818 Remote Similarity NPC610917
0.5714 Remote Similarity NPC165711
0.5556 Remote Similarity NPC46536
0.5556 Remote Similarity NPC138139
0.5556 Remote Similarity NPC603180
0.5517 Remote Similarity NPC610334
0.5439 Remote Similarity NPC109854
0.5424 Remote Similarity NPC483605
0.5088 Remote Similarity NPC290445
0.5085 Remote Similarity NPC302661
0.5082 Remote Similarity NPC65661

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC68620 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