Natural Product: NPC600801

Natural Product IDNPC600801
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 VJRFPARLIPMNRA-HOTGVXAUSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL3753783
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 VJRFPARLIPMNRA-HOTGVXAUSA-N
Standard InCHI InChI=1S/C20H20O5/c1-3-17-19(24-11-22-17)7-13(1)5-15-9-21-10-16(15)6-14-2-4-18-20(8-14)25-12-23-18/h1-4,7-8,15-16H,5-6,9-12H2/t15-,16-/m0/s1
SMILES c1cc2c(cc1C[C@H]1COC[C@@H]1Cc1ccc3c(c1)OCO3)OCO2

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   340.13 Volume:   339.826
?
Van der Waals volume.
Dense:   1.001 LogP:   2.618
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.557
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.291
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   25.0
TPSA:   46.15
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   0.0 Rings:   5.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.855 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.255 Fsp3:   0.4
MCE-18:   78.857
?
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:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.481 Fluc inhibitor:   0.734
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.031
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.075
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.303 Promiscuous compounds:   0.133

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.785 MDCK Permeability:   -4.685
Pgp-inhibitor:   0.926 Pgp-substrate:   0.028
PAMPA:   0.063
?
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):   0.0
20% Bioavailability (F20%):   0.084 30% Bioavailability (F30%):   0.0
50% Bioavailability (F50%):   0.259

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.955 MRP1:   0.528
Plasma Protein Binding (PPB):   96.592% Volume Distribution (VD):   0.449
Fu: 4.716%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.971
OATP1B3 inhibitor:   0.766 BCRP inhibitor:   0.011
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.998
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.994
CYP2C9-inhibitor:   1.0 CYP2C9-substrate:   1.0
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   1.0
CYP3A4-inhibitor:   0.986 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.994 CYP2C8-inhibitor:   0.002
HLM stability:   0.952
?
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):  3.967 Half-life (T1/2):  0.624

ADMET: Toxicity

hERG Blockers:  0.374 hERG Blockers (10um):  0.466
Human Hepatotoxicity (H-HT):  0.964 Drug-induced Liver Injury (DILI):  0.996
AMES Toxicity:  0.849 Rat Oral Acute Toxicity:  0.312
Maximum Recommended Daily Dose:  0.431 Skin Sensitization:  0.959
Carcinogencity:  0.882 Eye Corrosion:  0.005
Eye Irritation:  0.927 Respiratory Toxicity:  0.371
Drug-induced Neurotoxicity:  0.961 Ototoxicity:  0.703
Hematotoxicity:  0.436 Drug-induced Nephrotoxicity:  0.909
Genotoxicity:  0.934 RPMI-8226 Immunitoxicity:  0.192
A549 Cytotoxicity:  0.24 Hek293 Cytotoxicity:  0.561
BCF:   2.26
?
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:   4.482
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.145
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.531
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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
NPO8188 Hypoestes purpurea Species Acanthaceae Eukaryota n.a. n.a. n.a. PMID[15568798]
NPO6978 Boronella koniambiensis Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[16038554]
NPO8188 Hypoestes purpurea Species Acanthaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO6978 Boronella koniambiensis Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8188 Hypoestes purpurea Species Acanthaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO8188 Hypoestes purpurea Species Acanthaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO6978 Boronella koniambiensis Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8188 Hypoestes purpurea Species Acanthaceae 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
NPT466 Cell line U-937 Homo sapiens Activity n.a. n.a. n.a. PMID[26774581]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 40200.0 nM PMID[26774581]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 51100.0 nM PMID[26774581]

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 NPC600801 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
0.8537 High Similarity NPC192255
0.8 Intermediate Similarity NPC476748
0.7083 Intermediate Similarity NPC18576
0.6957 Remote Similarity NPC143895
0.6889 Remote Similarity NPC110958
0.6889 Remote Similarity NPC19890
0.6739 Remote Similarity NPC171550
0.6739 Remote Similarity NPC134764
0.6667 Remote Similarity NPC80241
0.6667 Remote Similarity NPC301641
0.6667 Remote Similarity NPC485483
0.6596 Remote Similarity NPC158737
0.6327 Remote Similarity NPC205915
0.6275 Remote Similarity NPC47181
0.619 Remote Similarity NPC40352
0.619 Remote Similarity NPC213711
0.6098 Remote Similarity NPC81067
0.6098 Remote Similarity NPC602945
0.6078 Remote Similarity NPC176586
0.6078 Remote Similarity NPC210354
0.6047 Remote Similarity NPC344161
0.5962 Remote Similarity NPC185908
0.5962 Remote Similarity NPC191158
0.5962 Remote Similarity NPC177644
0.5962 Remote Similarity NPC482891
0.58 Remote Similarity NPC165128
0.575 Remote Similarity NPC31279
0.5745 Remote Similarity NPC11453
0.566 Remote Similarity NPC230968
0.566 Remote Similarity NPC102260
0.5536 Remote Similarity NPC145569
0.551 Remote Similarity NPC474288
0.5439 Remote Similarity NPC487679
0.5439 Remote Similarity NPC56184
0.5439 Remote Similarity NPC487678
0.5417 Remote Similarity NPC249788
0.5417 Remote Similarity NPC485482
0.5417 Remote Similarity NPC196937
0.5417 Remote Similarity NPC606623
0.5345 Remote Similarity NPC282291
0.5345 Remote Similarity NPC166137
0.5345 Remote Similarity NPC169973
0.5273 Remote Similarity NPC3982
0.5227 Remote Similarity NPC604144
0.5217 Remote Similarity NPC171928
0.5217 Remote Similarity NPC158526
0.5217 Remote Similarity NPC129687
0.5217 Remote Similarity NPC33611
0.5217 Remote Similarity NPC16830
0.5217 Remote Similarity NPC100223
0.52 Remote Similarity NPC104077
0.52 Remote Similarity NPC219671
0.52 Remote Similarity NPC147616
0.52 Remote Similarity NPC485480
0.5082 Remote Similarity NPC156376

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC600801 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
0.5111 Remote Similarity NPD554 Phase 3

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