Natural Product: NPC603655

Natural Product IDNPC603655
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 WKSRJSLONFSQMS-ZUOSLIMISA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL456082
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 WKSRJSLONFSQMS-ZUOSLIMISA-N
Standard InCHI InChI=1S/C25H28O14/c1-33-11-5-9(6-12(34-2)16(11)27)22-24(36-4)19(30)15-10(37-22)7-13(23(35-3)18(15)29)38-25-21(32)20(31)17(28)14(8-26)39-25/h5-7,14,17,20-21,25-29,31-32H,8H2,1-4H3/t14-,17-,20+,21-,25-/m1/s1
SMILES COc1cc(-c2oc3cc(O[C@@H]4O[C@H](CO)[C@@H](O)[C@H](O)[C@H]4O)c(OC)c(O)c3c(=O)c2OC)cc(OC)c1O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   552.15 Volume:   508.702
?
Van der Waals volume.
Dense:   1.085 LogP:   0.771
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.177
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.899
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   8.0 Rigid Bonds:   24.0
TPSA:   206.97
?
Topological Polar Surface Area.
 H-Bond Acceptor:   14.0
H-Bond Donor:   6.0 Rings:   4.0
Heavy Atoms:   14.0

MedChem Properties

QED Drug-Likeness Score:   0.219 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.135 Fsp3:   0.4
MCE-18:   95.286
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Accepted
Pfizer Rule:   Rejected GSK Rule:   Accepted
Golden Triangle Rule:   Accepted BMS Rule:   0
Chelating Alert:   1 PAINS Alert:   0
Colloidal aggregators:   0.498 Fluc inhibitor:   0.179
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.783
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.83
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.081 Promiscuous compounds:   0.617

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.098 MDCK Permeability:   -5.435
Pgp-inhibitor:   0.304 Pgp-substrate:   0.143
PAMPA:   0.372
?
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):   0.865
20% Bioavailability (F20%):   0.009 30% Bioavailability (F30%):   0.639
50% Bioavailability (F50%):   0.996

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.003 MRP1:   0.561
Plasma Protein Binding (PPB):   91.137% Volume Distribution (VD):   -0.256
Fu: 8.698%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.957
BSEP inhibitor:   0.35

ADMET: Metabolism

CYP1A2-inhibitor:   0.161 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.003 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.001
CYP3A4-inhibitor:   0.002 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.312
HLM stability:   0.076
?
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):  2.629 Half-life (T1/2):  3.735

ADMET: Toxicity

hERG Blockers:  0.017 hERG Blockers (10um):  0.107
Human Hepatotoxicity (H-HT):  0.65 Drug-induced Liver Injury (DILI):  0.929
AMES Toxicity:  0.784 Rat Oral Acute Toxicity:  0.031
Maximum Recommended Daily Dose:  0.038 Skin Sensitization:  0.99
Carcinogencity:  0.482 Eye Corrosion:  0.0
Eye Irritation:  0.181 Respiratory Toxicity:  0.029
Drug-induced Neurotoxicity:  0.018 Ototoxicity:  0.858
Hematotoxicity:  0.397 Drug-induced Nephrotoxicity:  0.544
Genotoxicity:  0.413 RPMI-8226 Immunitoxicity:  0.167
A549 Cytotoxicity:  0.231 Hek293 Cytotoxicity:  0.278
BCF:   0.381
?
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:   3.062
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.325
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.598
?
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
NPO9607 Tillandsia usneoides Species Bromeliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9607 Tillandsia usneoides Species Bromeliaceae 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
NPT32 Organism Mus musculus Mus musculus Activity = -1.0 % PMID[7595594]





 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
- Artemia LC50 = 420.0 ppm PMID[7595594]

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 NPC603655 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
0.8026 Intermediate Similarity NPC488072
0.8 Intermediate Similarity NPC21666
0.7632 Intermediate Similarity NPC488071
0.7368 Intermediate Similarity NPC24043
0.7051 Intermediate Similarity NPC325555
0.7051 Intermediate Similarity NPC226304
0.679 Remote Similarity NPC602805
0.65 Remote Similarity NPC186807
0.65 Remote Similarity NPC105025
0.6463 Remote Similarity NPC101026
0.6463 Remote Similarity NPC488077
0.642 Remote Similarity NPC117260
0.642 Remote Similarity NPC201292
0.6341 Remote Similarity NPC609451
0.6296 Remote Similarity NPC84362
0.625 Remote Similarity NPC58053
0.6098 Remote Similarity NPC27640
0.6098 Remote Similarity NPC488080
0.6098 Remote Similarity NPC169977
0.6071 Remote Similarity NPC605067
0.6049 Remote Similarity NPC289667
0.604 Remote Similarity NPC488079
0.6024 Remote Similarity NPC42773
0.6024 Remote Similarity NPC45522
0.5977 Remote Similarity NPC473682
0.5976 Remote Similarity NPC93337
0.593 Remote Similarity NPC203050
0.593 Remote Similarity NPC225434
0.5904 Remote Similarity NPC45638
0.5882 Remote Similarity NPC609478
0.5783 Remote Similarity NPC297987
0.5783 Remote Similarity NPC136042
0.5765 Remote Similarity NPC224462
0.5747 Remote Similarity NPC48773
0.5728 Remote Similarity NPC488078
0.5714 Remote Similarity NPC607530
0.5698 Remote Similarity NPC120099
0.5647 Remote Similarity NPC222936
0.5647 Remote Similarity NPC472459
0.5647 Remote Similarity NPC205076
0.5632 Remote Similarity NPC206123
0.5632 Remote Similarity NPC307518
0.5595 Remote Similarity NPC64305
0.5591 Remote Similarity NPC483415
0.5568 Remote Similarity NPC469931
0.5532 Remote Similarity NPC483416
0.5517 Remote Similarity NPC148710
0.5476 Remote Similarity NPC19388
0.5476 Remote Similarity NPC240431
0.5476 Remote Similarity NPC77672
0.5476 Remote Similarity NPC55786
0.5476 Remote Similarity NPC133671
0.5476 Remote Similarity NPC135391
0.5476 Remote Similarity NPC78263
0.5476 Remote Similarity NPC250069
0.5467 Remote Similarity NPC261004
0.5455 Remote Similarity NPC116458
0.5455 Remote Similarity NPC246943
0.5455 Remote Similarity NPC311830
0.5455 Remote Similarity NPC605784
0.5455 Remote Similarity NPC607707
0.5444 Remote Similarity NPC251417
0.5426 Remote Similarity NPC483414
0.5412 Remote Similarity NPC145038
0.5412 Remote Similarity NPC56077
0.5412 Remote Similarity NPC281131
0.5412 Remote Similarity NPC253662
0.5412 Remote Similarity NPC179950
0.5412 Remote Similarity NPC88789
0.5412 Remote Similarity NPC491374
0.5402 Remote Similarity NPC168584
0.5402 Remote Similarity NPC60735
0.5402 Remote Similarity NPC26230
0.5393 Remote Similarity NPC601586
0.5385 Remote Similarity NPC609888
0.5341 Remote Similarity NPC243930
0.53 Remote Similarity NPC473072
0.5287 Remote Similarity NPC599850
0.5233 Remote Similarity NPC95090
0.5233 Remote Similarity NPC27408
0.52 Remote Similarity NPC176300
0.5169 Remote Similarity NPC22832
0.5169 Remote Similarity NPC284960
0.5169 Remote Similarity NPC486578
0.5169 Remote Similarity NPC601144
0.5158 Remote Similarity NPC488073
0.5135 Remote Similarity NPC110070
0.5135 Remote Similarity NPC101830
0.5132 Remote Similarity NPC25495
0.5116 Remote Similarity NPC261866
0.5116 Remote Similarity NPC110349
0.5116 Remote Similarity NPC45618
0.5111 Remote Similarity NPC88023
0.5111 Remote Similarity NPC309025
0.5109 Remote Similarity NPC480463
0.5067 Remote Similarity NPC18772
0.5057 Remote Similarity NPC8573
0.5057 Remote Similarity NPC146792
0.5057 Remote Similarity NPC158674
0.5056 Remote Similarity NPC611303
0.5054 Remote Similarity NPC480466

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC603655 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