Natural Product: NPC603895

Natural Product IDNPC603895
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 DTDADHMBRZKXSC-GKASHWOUSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL525626
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 DTDADHMBRZKXSC-GKASHWOUSA-N
Standard InCHI InChI=1S/C22H26N2O4/c1-12-17-10-24-7-6-14-16-8-13(26-2)4-5-19(16)23-21(14)20(24)9-15(17)18(11-28-12)22(25)27-3/h4-5,8,11-12,15,17,20,23H,6-7,9-10H2,1-3H3/t12-,15-,17-,20-/m0/s1
SMILES COC(=O)C1=CO[C@@H](C)[C@@H]2CN3CCc4c([nH]c5ccc(OC)cc45)[C@@H]3C[C@H]12

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   382.19 Volume:   387.622
?
Van der Waals volume.
Dense:   0.986 LogP:   2.406
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.453
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.365
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   26.0
TPSA:   63.79
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   1.0 Rings:   5.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.809 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.979 Fsp3:   0.5
MCE-18:   94.091
?
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:   0.202 Fluc inhibitor:   0.366
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.881
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.232
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.002 Promiscuous compounds:   0.571

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.75 MDCK Permeability:   -4.726
Pgp-inhibitor:   0.033 Pgp-substrate:   0.635
PAMPA:   0.005
?
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%):   0.319 30% Bioavailability (F30%):   0.359
50% Bioavailability (F50%):   0.967

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.564 MRP1:   1.0
Plasma Protein Binding (PPB):   86.367% Volume Distribution (VD):   0.502
Fu: 14.432%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.657
OATP1B3 inhibitor:   0.863 BCRP inhibitor:   0.892
BSEP inhibitor:   0.996

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.082
CYP2C19-inhibitor:   0.991 CYP2C19-substrate:   0.114
CYP2C9-inhibitor:   0.005 CYP2C9-substrate:   0.999
CYP2D6-inhibitor:   0.995 CYP2D6-substrate:   0.953
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.732
HLM stability:   0.239
?
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):  10.694 Half-life (T1/2):  1.367

ADMET: Toxicity

hERG Blockers:  0.69 hERG Blockers (10um):  0.604
Human Hepatotoxicity (H-HT):  0.465 Drug-induced Liver Injury (DILI):  0.752
AMES Toxicity:  0.787 Rat Oral Acute Toxicity:  0.872
Maximum Recommended Daily Dose:  0.983 Skin Sensitization:  0.344
Carcinogencity:  0.804 Eye Corrosion:  0.0
Eye Irritation:  0.074 Respiratory Toxicity:  0.981
Drug-induced Neurotoxicity:  0.897 Ototoxicity:  0.52
Hematotoxicity:  0.342 Drug-induced Nephrotoxicity:  0.928
Genotoxicity:  0.986 RPMI-8226 Immunitoxicity:  0.113
A549 Cytotoxicity:  0.712 Hek293 Cytotoxicity:  0.702
BCF:   1.018
?
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:   3.715
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.152
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.521
?
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
NPO33625 Ochrosia moorei Species Apocynaceae Eukaryota stems and leaves Natural Arch National Park, McPherson Range, in South East Queensland 1995-MAR PMID[18412397]
NPO33625 Ochrosia moorei Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO59799 Aspidosperma marcgravianum Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO55734 Cinchona pelletierana Genus Rubiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO53072 Rauvolfia canescens Genus Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO49604 Rauwolfia canescens n.a. n.a. n.a. 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
NPT459 Individual protein Human immunodeficiency virus type 1 reverse transcriptase Human immunodeficiency virus 1 IC50 > 200.0 ug.mL-1 PMID[1710653]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT992 Organism Entamoeba histolytica Entamoeba histolytica IC50 = 3.6 ug.mL-1 DOI[10.1007/s00044-011-9767-1]
NPT6 Organism Plasmodium falciparum Plasmodium falciparum IC50 = 0.3 ug.mL-1 PMID[34058709]
NPT6 Organism Plasmodium falciparum Plasmodium falciparum IC50 = 690.0 nM PMID[34058709]

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 NPC603895 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
0.8101 Intermediate Similarity NPC21638
0.7949 Intermediate Similarity NPC312870
0.7949 Intermediate Similarity NPC199851
0.7949 Intermediate Similarity NPC294909
0.7949 Intermediate Similarity NPC254240
0.7949 Intermediate Similarity NPC128265
0.7949 Intermediate Similarity NPC604675
0.6118 Remote Similarity NPC486449
0.6118 Remote Similarity NPC63199
0.6118 Remote Similarity NPC111602
0.6118 Remote Similarity NPC102338
0.6118 Remote Similarity NPC196251
0.5977 Remote Similarity NPC100898
0.5977 Remote Similarity NPC148183
0.5977 Remote Similarity NPC21084
0.5977 Remote Similarity NPC152768
0.5977 Remote Similarity NPC605270
0.593 Remote Similarity NPC273374
0.5795 Remote Similarity NPC131260
0.5326 Remote Similarity NPC293861
0.5165 Remote Similarity NPC107782
0.5165 Remote Similarity NPC486454

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC603895 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
0.7949 Intermediate Similarity NPD4500 Approved
0.7949 Intermediate Similarity NPD4501 Approved

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