Natural Product: NPC219162

Natural Product IDNPC219162
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (+/-)-Deoxytylophorinine
IUPAC Name 3,6,7-trimethoxy-9,11,12,13,13a,14-hexahydrophenanthro[9,10-f]indolizine
Synonyms (+/-)-Deoxypergularinine
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL497756
PubChem CID 6426880
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0002448] Benzenoids
      • [CHEMONTID:0000025] Phenanthrenes and derivatives
        • [CHEMONTID:0001906] Phenanthroindolizidines

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 RFPUTOSCASFEEO-UHFFFAOYSA-N
Standard InCHI InChI=1S/C23H25NO3/c1-25-15-6-7-16-17-9-14-5-4-8-24(14)13-21(17)20-12-23(27-3)22(26-2)11-19(20)18(16)10-15/h6-7,10-12,14H,4-5,8-9,13H2,1-3H3
SMILES COc1ccc2c3CC4CCCN4Cc3c3cc(c(cc3c2c1)OC)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   363.18 Volume:   382.494
?
Van der Waals volume.
Dense:   0.95 LogP:   3.38
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.166
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.099
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   25.0
TPSA:   30.93
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   0.0 Rings:   5.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.639 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.868 Fsp3:   0.391
MCE-18:   87.75
?
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:   0.891 Fluc inhibitor:   0.018
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.787
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.412
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.001 Promiscuous compounds:   0.274

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.487 MDCK Permeability:   -4.691
Pgp-inhibitor:   0.663 Pgp-substrate:   0.069
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):   0.004
20% Bioavailability (F20%):   0.019 30% Bioavailability (F30%):   0.012
50% Bioavailability (F50%):   0.638

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.419 MRP1:   0.976
Plasma Protein Binding (PPB):   82.649% Volume Distribution (VD):   0.235
Fu: 13.357%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.98
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   0.981
BSEP inhibitor:   0.994

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.032
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.004
CYP2C9-inhibitor:   0.999 CYP2C9-substrate:   0.934
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.406
CYP3A4-inhibitor:   0.824 CYP3A4-substrate:   0.565
CYP2B6-substrate:   1.0 CYP2C8-inhibitor:   0.119
HLM stability:   0.973
?
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):  8.086 Half-life (T1/2):  1.173

ADMET: Toxicity

hERG Blockers:  0.923 hERG Blockers (10um):  0.773
Human Hepatotoxicity (H-HT):  0.766 Drug-induced Liver Injury (DILI):  0.137
AMES Toxicity:  0.785 Rat Oral Acute Toxicity:  0.823
Maximum Recommended Daily Dose:  0.964 Skin Sensitization:  0.522
Carcinogencity:  0.887 Eye Corrosion:  0.0
Eye Irritation:  0.002 Respiratory Toxicity:  0.997
Drug-induced Neurotoxicity:  0.967 Ototoxicity:  0.938
Hematotoxicity:  0.417 Drug-induced Nephrotoxicity:  0.565
Genotoxicity:  0.662 RPMI-8226 Immunitoxicity:  0.129
A549 Cytotoxicity:  0.484 Hek293 Cytotoxicity:  0.889
BCF:   2.158
?
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:   4.379
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.851
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.185
?
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
NPO7304 Ficus hispida Species Moraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO7304 Ficus hispida Species Moraceae 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
NPT81 Cell line A549 Homo sapiens EC50 = 0.011 ug.mL-1 PMID[18456501]
NPT83 Cell line MCF7 Homo sapiens EC50 = 0.043 ug.mL-1 PMID[18456501]
NPT91 Cell line KB Homo sapiens EC50 = 0.023 ug.mL-1 PMID[18456501]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. EC50 = 0.016 ug.mL-1 PMID[18456501]
NPT88 Organism Mycobacterium tuberculosis Mycobacterium tuberculosis MIC = 6.25 ug.mL-1 PMID[28628823]
NPT786 Organism Tobacco mosaic virus Tobacco mosaic virus Activity = 26.1 % PMID[20000413]
NPT786 Organism Tobacco mosaic virus Tobacco mosaic virus Activity = 67.4 % PMID[20000413]
NPT786 Organism Tobacco mosaic virus Tobacco mosaic virus Activity = 60.0 % PMID[20000413]
NPT786 Organism Tobacco mosaic virus Tobacco mosaic virus EC50 < 25.0 ug.mL-1 PMID[20000413]
NPT786 Organism Tobacco mosaic virus Tobacco mosaic virus Inhibition = 79.2 % PMID[20000413]
NPT786 Organism Tobacco mosaic virus Tobacco mosaic virus Inhibition = 65.0 % PMID[20000413]
NPT786 Organism Tobacco mosaic virus Tobacco mosaic virus Inhibition = 66.7 % PMID[20000413]
NPT786 Organism Tobacco mosaic virus Tobacco mosaic virus Inhibition = 75.0 % PMID[20000413]

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 NPC219162 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 NPC605089
0.9245 High Similarity NPC90844
0.9245 High Similarity NPC95075
0.9245 High Similarity NPC253883
0.8909 High Similarity NPC92541
0.8305 Intermediate Similarity NPC76079
0.8269 Intermediate Similarity NPC130941
0.8269 Intermediate Similarity NPC605913
0.7797 Intermediate Similarity NPC244112
0.75 Intermediate Similarity NPC603531
0.7031 Intermediate Similarity NPC487714
0.6667 Remote Similarity NPC186063
0.6349 Remote Similarity NPC233650
0.6094 Remote Similarity NPC150879
0.5672 Remote Similarity NPC169743
0.5606 Remote Similarity NPC487715
0.5429 Remote Similarity NPC487711
0.5429 Remote Similarity NPC487712
0.5429 Remote Similarity NPC487713

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC219162 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