Natural Product: NPC488659

Natural Product IDNPC488659
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 RJHZJSVRHVAVEE-SFJWVRJRSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]

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 RJHZJSVRHVAVEE-SFJWVRJRSA-N
Standard InCHI InChI=1S/C25H36O7/c1-8-14(2)9-10-24(6)15(3)11-21(28)25-19(12-18(13-20(24)25)30-16(4)26)22(29-7)32-23(25)31-17(5)27/h8-9,12,15,18,20-23,28H,1,10-11,13H2,2-7H3/b14-9+/t15-,18-,20+,21+,22+,23-,24-,25-/m1/s1
SMILES C=C/C(=C/C[C@]1(C)[C@H](C)C[C@@H]([C@@]23C(=C[C@H](C[C@@H]12)OC(=O)C)[C@@H](OC)O[C@H]3OC(=O)C)O)/C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   448.25 Volume:   463.636
?
Van der Waals volume.
Dense:   0.967 LogP:   2.783
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.912
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.721
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   8.0 Rigid Bonds:   19.0
TPSA:   91.29
?
Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   1.0 Rings:   3.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.377 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   5.763 Fsp3:   0.68
MCE-18:   86.905
?
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:   0.449 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.007
?
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:   0.332 Promiscuous compounds:   0.506

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.256 MDCK Permeability:   -4.906
Pgp-inhibitor:   0.987 Pgp-substrate:   0.908
PAMPA:   0.242
?
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):   0.062
20% Bioavailability (F20%):   0.995 30% Bioavailability (F30%):   0.999
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.924
Plasma Protein Binding (PPB):   66.079% Volume Distribution (VD):   -0.304
Fu: 28.343%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   0.97 BCRP inhibitor:   0.472
BSEP inhibitor:   0.99

ADMET: Metabolism

CYP1A2-inhibitor:   0.015 CYP1A2-substrate:   0.117
CYP2C19-inhibitor:   0.001 CYP2C19-substrate:   0.013
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.874
CYP2D6-inhibitor:   0.013 CYP2D6-substrate:   0.02
CYP3A4-inhibitor:   0.001 CYP3A4-substrate:   0.931
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.976
?
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):  7.857 Half-life (T1/2):  1.264

ADMET: Toxicity

hERG Blockers:  0.097 hERG Blockers (10um):  0.352
Human Hepatotoxicity (H-HT):  0.522 Drug-induced Liver Injury (DILI):  0.791
AMES Toxicity:  0.91 Rat Oral Acute Toxicity:  0.952
Maximum Recommended Daily Dose:  0.977 Skin Sensitization:  0.909
Carcinogencity:  0.559 Eye Corrosion:  0.0
Eye Irritation:  0.085 Respiratory Toxicity:  0.927
Drug-induced Neurotoxicity:  0.727 Ototoxicity:  0.676
Hematotoxicity:  0.678 Drug-induced Nephrotoxicity:  0.752
Genotoxicity:  0.99 RPMI-8226 Immunitoxicity:  0.272
A549 Cytotoxicity:  0.474 Hek293 Cytotoxicity:  0.338
BCF:   0.851
?
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:   3.727
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.575
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.96
?
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
NPO40063 Casearia graveolens Species Salicaceae Eukaryota n.a. n.a. n.a. PMID[26474353]
NPO40063 Casearia graveolens Species Salicaceae Eukaryota Leaves n.a. n.a. PMID[31916761]

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
NPT81 Cell line A549 Homo sapiens IC50 > 10000.0 nM PMID[31916761]
NPT65 Cell line HepG2 Homo sapiens IC50 > 10000.0 nM PMID[31916761]

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 NPC488659 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 NPC604149
0.9286 High Similarity NPC602188
0.9138 High Similarity NPC134270
0.9138 High Similarity NPC488660
0.9138 High Similarity NPC488657
0.9138 High Similarity NPC488654
0.9138 High Similarity NPC609880
0.8983 High Similarity NPC488658
0.8983 High Similarity NPC488655
0.8689 High Similarity NPC252296
0.85 High Similarity NPC201880
0.85 High Similarity NPC81567
0.85 High Similarity NPC329623
0.85 High Similarity NPC488652
0.85 High Similarity NPC609711
0.8475 Intermediate Similarity NPC488653
0.8475 Intermediate Similarity NPC488656
0.8361 Intermediate Similarity NPC330003
0.8361 Intermediate Similarity NPC470321
0.8361 Intermediate Similarity NPC264867
0.8361 Intermediate Similarity NPC473207
0.8361 Intermediate Similarity NPC609715
0.8095 Intermediate Similarity NPC488964
0.8095 Intermediate Similarity NPC184512
0.7083 Intermediate Similarity NPC109376
0.7077 Intermediate Similarity NPC479491
0.697 Remote Similarity NPC238397
0.6806 Remote Similarity NPC116292
0.6769 Remote Similarity NPC479943
0.6667 Remote Similarity NPC119550
0.6567 Remote Similarity NPC479940
0.6567 Remote Similarity NPC7644
0.6567 Remote Similarity NPC316974
0.6567 Remote Similarity NPC479497
0.6471 Remote Similarity NPC475889
0.6471 Remote Similarity NPC7613
0.6471 Remote Similarity NPC479942
0.6377 Remote Similarity NPC479941
0.6324 Remote Similarity NPC311223
0.629 Remote Similarity NPC604446
0.6286 Remote Similarity NPC471363
0.6111 Remote Similarity NPC127933
0.6061 Remote Similarity NPC606965
0.6 Remote Similarity NPC603601
0.597 Remote Similarity NPC600724
0.5714 Remote Similarity NPC179128
0.557 Remote Similarity NPC486751
0.5556 Remote Similarity NPC224660
0.5493 Remote Similarity NPC473204
0.5429 Remote Similarity NPC88507
0.5429 Remote Similarity NPC488235
0.5412 Remote Similarity NPC320734
0.5375 Remote Similarity NPC316708
0.5342 Remote Similarity NPC217921
0.5342 Remote Similarity NPC135015
0.5342 Remote Similarity NPC218158
0.5316 Remote Similarity NPC87630
0.5205 Remote Similarity NPC311166
0.5205 Remote Similarity NPC128795
0.5135 Remote Similarity NPC88013
0.5062 Remote Similarity NPC162569
0.5062 Remote Similarity NPC35160

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC488659 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