Natural Product: NPC472757

Natural Product IDNPC472757
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 VLQRBYYAEZBEJX-IXSMXENYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL3582004
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0000259] Prenol lipids
        • [CHEMONTID:0001551] Diterpenoids
          • [CHEMONTID:0002875] Tigliane and ingenane 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 VLQRBYYAEZBEJX-IXSMXENYSA-N
Standard InCHI InChI=1S/C27H38O7/c1-8-13(2)24(31)34-27-22(25(27,6)7)20-11-17(12-28)10-18-19(9-14(3)21(18)30)26(20,32)15(4)23(27)33-16(5)29/h9,11,13,15,18-20,22-23,28,32H,8,10,12H2,1-7H3/t13?,15-,18-,19-,20+,22-,23-,26+,27-/m1/s1
SMILES OCC1=C[C@H]2[C@@H]3C([C@]3(OC(=O)C(CC)C)[C@@H]([C@H]([C@@]2([C@H]2[C@@H](C1)C(=O)C(=C2)C)O)C)OC(=O)C)(C)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   474.26 Volume:   489.672
?
Van der Waals volume.
Dense:   0.969 LogP:   2.681
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.864
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.963
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   7.0 Rigid Bonds:   21.0
TPSA:   110.13
?
Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   2.0 Rings:   4.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.466 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   5.217 Fsp3:   0.741
MCE-18:   80.043
?
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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.243 Fluc inhibitor:   0.001
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.005
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.0
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.31 Promiscuous compounds:   0.383

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.105 MDCK Permeability:   -4.821
Pgp-inhibitor:   0.967 Pgp-substrate:   0.769
PAMPA:   0.684
?
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):   0.315
20% Bioavailability (F20%):   0.999 30% Bioavailability (F30%):   1.0
50% Bioavailability (F50%):   0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.01 MRP1:   0.95
Plasma Protein Binding (PPB):   64.097% Volume Distribution (VD):   -0.156
Fu: 35.84%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.992
OATP1B3 inhibitor:   0.377 BCRP inhibitor:   0.0
BSEP inhibitor:   0.996

ADMET: Metabolism

CYP1A2-inhibitor:   0.003 CYP1A2-substrate:   0.001
CYP2C19-inhibitor:   0.062 CYP2C19-substrate:   0.001
CYP2C9-inhibitor:   0.012 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.105
CYP3A4-inhibitor:   0.927 CYP3A4-substrate:   0.029
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.885
HLM stability:   0.419
?
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):  8.094 Half-life (T1/2):  0.949

ADMET: Toxicity

hERG Blockers:  0.072 hERG Blockers (10um):  0.255
Human Hepatotoxicity (H-HT):  0.662 Drug-induced Liver Injury (DILI):  0.66
AMES Toxicity:  0.579 Rat Oral Acute Toxicity:  0.263
Maximum Recommended Daily Dose:  0.129 Skin Sensitization:  0.902
Carcinogencity:  0.678 Eye Corrosion:  0.021
Eye Irritation:  0.408 Respiratory Toxicity:  0.527
Drug-induced Neurotoxicity:  0.345 Ototoxicity:  0.661
Hematotoxicity:  0.817 Drug-induced Nephrotoxicity:  0.561
Genotoxicity:  0.187 RPMI-8226 Immunitoxicity:  0.142
A549 Cytotoxicity:  0.312 Hek293 Cytotoxicity:  0.3
BCF:   0.584
?
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:   3.349
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.176
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.546
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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
NPO33329 stillingia lineata Species Euphorbiaceae Eukaryota Leaves Langevin, La Reunion, France 2009-Nov PMID[25946116]
NPO33329 stillingia lineata Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]

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
NPT393 Cell line HCT-116 Homo sapiens Inhibition < 40.0 % PMID[17844994]
NPT83 Cell line MCF7 Homo sapiens Inhibition < 40.0 % PMID[10425119]
NPT306 Cell line PC-3 Homo sapiens Inhibition < 40.0 % PMID[2614419]
NPT189 Cell line Vero Chlorocebus aethiops CC50 = 105000.0 nM PMID[15844965]
NPT25 Cell line MT4 Homo sapiens CC50 = 85000.0 nM PMID[3404149]
NPT332 Organism Human immunodeficiency virus type 2 (ISOLATE ROD) Human immunodeficiency virus type 2 (ISOLATE ROD) EC50 = 13000.0 nM PMID[21504848]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. EC50 = 77000.0 nM PMID[25946116]
NPT24 Organism Human immunodeficiency virus 1 Human immunodeficiency virus 1 EC50 > 85000.0 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Ratio CC50/EC50 = 4.0 n.a. PMID[17181158]
NPT2 Others Unspecified n.a. Ratio CC50/EC50 = 1.4 n.a. DrugMatrix in vivo data: Biochemistry

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 NPC472757 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
0.9322 High Similarity NPC481522
0.8983 High Similarity NPC482406
0.8852 High Similarity NPC481520
0.873 High Similarity NPC471127
0.873 High Similarity NPC481531
0.7846 Intermediate Similarity NPC234858
0.7846 Intermediate Similarity NPC179207
0.7812 Intermediate Similarity NPC154363
0.7612 Intermediate Similarity NPC481525
0.7465 Intermediate Similarity NPC481523
0.7463 Intermediate Similarity NPC485737
0.7353 Intermediate Similarity NPC476111
0.7246 Intermediate Similarity NPC90814
0.7246 Intermediate Similarity NPC189393
0.7246 Intermediate Similarity NPC608501
0.7101 Intermediate Similarity NPC481528
0.7083 Intermediate Similarity NPC482221
0.7042 Intermediate Similarity NPC236918
0.7042 Intermediate Similarity NPC156745
0.6986 Remote Similarity NPC482220
0.6892 Remote Similarity NPC482222
0.6806 Remote Similarity NPC10721
0.68 Remote Similarity NPC482219
0.6667 Remote Similarity NPC472758
0.6622 Remote Similarity NPC472759
0.6447 Remote Similarity NPC329080
0.6338 Remote Similarity NPC482405
0.6324 Remote Similarity NPC481530
0.6324 Remote Similarity NPC472400
0.6203 Remote Similarity NPC140021
0.6154 Remote Similarity NPC611138
0.6049 Remote Similarity NPC112752
0.6049 Remote Similarity NPC311054
0.6027 Remote Similarity NPC485734
0.5915 Remote Similarity NPC472397
0.589 Remote Similarity NPC471125
0.5867 Remote Similarity NPC471126
0.5753 Remote Similarity NPC472401
0.5571 Remote Similarity NPC481521
0.5455 Remote Similarity NPC471128
0.5417 Remote Similarity NPC481526
0.5342 Remote Similarity NPC600179
0.5342 Remote Similarity NPC602150
0.5333 Remote Similarity NPC605797
0.5316 Remote Similarity NPC22628
0.5195 Remote Similarity NPC275696
0.5195 Remote Similarity NPC145182
0.5195 Remote Similarity NPC255081
0.5181 Remote Similarity NPC472398
0.5181 Remote Similarity NPC600915
0.5176 Remote Similarity NPC482198
0.5067 Remote Similarity NPC171905
0.5063 Remote Similarity NPC472399
0.5059 Remote Similarity NPC21483
0.5059 Remote Similarity NPC198205

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC472757 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