Natural Product: NPC603180

Natural Product IDNPC603180
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 ZQHJXKYYELWEOK-UMGGQSCQSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL3633799
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 ZQHJXKYYELWEOK-UMGGQSCQSA-N
Standard InCHI InChI=1S/C20H28O3/c1-14-5-8-17-19(2,10-4-11-20(17,3)18(21)22)16(14)7-6-15-9-12-23-13-15/h9,12-13,16-17H,1,4-8,10-11H2,2-3H3,(H,21,22)/t16-,17+,19+,20+/m1/s1
SMILES C=C1CC[C@H]2[C@@](C)(CCC[C@]2(C)C(=O)O)[C@@H]1CCc1ccoc1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   316.2 Volume:   344.632
?
Van der Waals volume.
Dense:   0.918 LogP:   3.588
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.867
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.749
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   18.0
TPSA:   50.44
?
Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   1.0 Rings:   3.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.788 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.051 Fsp3:   0.65
MCE-18:   70.909
?
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:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.168 Fluc inhibitor:   0.001
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.014
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.009
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.434 Promiscuous compounds:   0.172

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.93 MDCK Permeability:   -4.68
Pgp-inhibitor:   0.571 Pgp-substrate:   0.0
PAMPA:   0.11
?
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):   0.002
20% Bioavailability (F20%):   0.016 30% Bioavailability (F30%):   0.027
50% Bioavailability (F50%):   0.079

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.007 MRP1:   0.622
Plasma Protein Binding (PPB):   98.055% Volume Distribution (VD):   -0.479
Fu: 1.679%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   0.982 BCRP inhibitor:   0.082
BSEP inhibitor:   0.991

ADMET: Metabolism

CYP1A2-inhibitor:   0.016 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.07 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.927 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.001 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.377 CYP3A4-substrate:   0.007
CYP2B6-substrate:   0.136 CYP2C8-inhibitor:   0.048
HLM stability:   0.0
?
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):  2.723 Half-life (T1/2):  0.959

ADMET: Toxicity

hERG Blockers:  0.123 hERG Blockers (10um):  0.156
Human Hepatotoxicity (H-HT):  0.701 Drug-induced Liver Injury (DILI):  0.893
AMES Toxicity:  0.238 Rat Oral Acute Toxicity:  0.432
Maximum Recommended Daily Dose:  0.686 Skin Sensitization:  0.904
Carcinogencity:  0.836 Eye Corrosion:  0.144
Eye Irritation:  0.971 Respiratory Toxicity:  0.863
Drug-induced Neurotoxicity:  0.086 Ototoxicity:  0.524
Hematotoxicity:  0.395 Drug-induced Nephrotoxicity:  0.74
Genotoxicity:  0.284 RPMI-8226 Immunitoxicity:  0.028
A549 Cytotoxicity:  0.084 Hek293 Cytotoxicity:  0.152
BCF:   1.381
?
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:   4.178
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.545
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.992
?
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
NPO15454 Vitex rotundifolia Species Lamiaceae Eukaryota Fruits n.a. n.a. PMID[10579867]
NPO15454 Vitex rotundifolia Species Lamiaceae Eukaryota subterranean part n.a. n.a. PMID[11374949]
NPO15454 Vitex rotundifolia Species Lamiaceae Eukaryota n.a. fruit n.a. PMID[11536386]
NPO15454 Vitex rotundifolia Species Lamiaceae Eukaryota fruits n.a. n.a. PMID[11975496]
NPO15454 Vitex rotundifolia Species Lamiaceae Eukaryota fruits n.a. n.a. PMID[24035341]
NPO15454 Vitex rotundifolia Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO50771 Ricinocarpos stylosus Genus Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26663 Polyalthia fragrans Species Annonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO56949 Ricinocarpus stylosus Genus Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15454 Vitex rotundifolia Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO15454 Vitex rotundifolia Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO15454 Vitex rotundifolia Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO15454 Vitex rotundifolia Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26663 Polyalthia fragrans Species Annonaceae 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
NPT633 Organism Leishmania donovani Leishmania donovani IC50 = 8.68 ug.mL-1 PMID[26520665]
NPT633 Organism Leishmania donovani Leishmania donovani IC90 > 10.0 ug.mL-1 PMID[26520665]
NPT1018 Organism Trypanosoma brucei Trypanosoma brucei IC50 = 3.87 ug.mL-1 PMID[26520665]
NPT1018 Organism Trypanosoma brucei Trypanosoma brucei IC90 = 8.12 ug.mL-1 PMID[26520665]

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 NPC603180 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 NPC46536
1.0 High Similarity NPC138139
0.623 Remote Similarity NPC485404
0.5507 Remote Similarity NPC16922
0.5484 Remote Similarity NPC488498
0.5484 Remote Similarity NPC61952
0.5484 Remote Similarity NPC481630
0.5484 Remote Similarity NPC603184
0.5469 Remote Similarity NPC18819
0.5469 Remote Similarity NPC46610
0.5397 Remote Similarity NPC198240
0.5397 Remote Similarity NPC237591
0.5397 Remote Similarity NPC72343
0.5397 Remote Similarity NPC36616
0.5397 Remote Similarity NPC3753
0.5312 Remote Similarity NPC59436
0.5231 Remote Similarity NPC471159
0.5231 Remote Similarity NPC123880
0.5231 Remote Similarity NPC91369
0.5217 Remote Similarity NPC130275
0.5152 Remote Similarity NPC269543
0.5152 Remote Similarity NPC247783
0.5152 Remote Similarity NPC239098
0.5079 Remote Similarity NPC485403

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC603180 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