Natural Product: NPC535693

Natural Product IDNPC535693
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 O-Methylarmepavine, (S)-
IUPAC Name (1~{S})-6,7-dimethoxy-1-[(4-methoxyphenyl)methyl]-2-methyl-3,4-dihydro-1~{H}-isoquinoline
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
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 LZJWNVLTWYMMDJ-SFHVURJKSA-N
Standard InCHI InChI=1S/C20H25NO3/c1-21-10-9-15-12-19(23-3)20(24-4)13-17(15)18(21)11-14-5-7-16(22-2)8-6-14/h5-8,12-13,18H,9-11H2,1-4H3/t18-/m0/s1
SMILES COC1=CC=C(C[C@H]2C3=CC(OC)=C(OC)C=C3CCN2C)C=C1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   327.18 Volume:   350.355
?
Van der Waals volume.
Dense:   0.934 LogP:   2.664
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.725
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.52
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   17.0
TPSA:   30.93
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   0.0 Rings:   3.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.841 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.488 Fsp3:   0.4
MCE-18:   54.643
?
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:   0.316 Fluc inhibitor:   0.235
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.428
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.471
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.007 Promiscuous compounds:   0.461

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.553 MDCK Permeability:   -4.556
Pgp-inhibitor:   0.99 Pgp-substrate:   0.087
PAMPA:   0.003
?
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):   0.086
20% Bioavailability (F20%):   0.509 30% Bioavailability (F30%):   0.152
50% Bioavailability (F50%):   0.884

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.225 MRP1:   0.739
Plasma Protein Binding (PPB):   53.792% Volume Distribution (VD):   0.205
Fu: 41.694%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.982
OATP1B3 inhibitor:   0.964 BCRP inhibitor:   0.916
BSEP inhibitor:   0.999

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.034
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.003
CYP2C9-inhibitor:   1.0 CYP2C9-substrate:   0.959
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.902
CYP3A4-inhibitor:   0.999 CYP3A4-substrate:   0.005
CYP2B6-substrate:   0.998 CYP2C8-inhibitor:   0.558
HLM stability:   0.994
?
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):  10.799 Half-life (T1/2):  2.453

ADMET: Toxicity

hERG Blockers:  0.48 hERG Blockers (10um):  0.611
Human Hepatotoxicity (H-HT):  0.694 Drug-induced Liver Injury (DILI):  0.212
AMES Toxicity:  0.596 Rat Oral Acute Toxicity:  0.302
Maximum Recommended Daily Dose:  0.775 Skin Sensitization:  0.454
Carcinogencity:  0.551 Eye Corrosion:  0.016
Eye Irritation:  0.747 Respiratory Toxicity:  0.646
Drug-induced Neurotoxicity:  0.893 Ototoxicity:  0.508
Hematotoxicity:  0.233 Drug-induced Nephrotoxicity:  0.331
Genotoxicity:  0.32 RPMI-8226 Immunitoxicity:  0.064
A549 Cytotoxicity:  0.078 Hek293 Cytotoxicity:  0.434
BCF:   1.734
?
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:   3.822
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.42
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.45
?
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
NPO2884 Annona squamosa Species Annonaceae Eukaryota seeds n.a. n.a. PMID[11141125]
NPO2884 Annona squamosa Species Annonaceae Eukaryota n.a. n.a. n.a. PMID[12398544]
NPO25677 Xylopia parviflora Species Annonaceae Eukaryota n.a. bark n.a. PMID[15081299]
NPO25677 Xylopia parviflora Species Annonaceae Eukaryota n.a. root n.a. PMID[15081299]
NPO2884 Annona squamosa Species Annonaceae Eukaryota n.a. n.a. n.a. PMID[18419154]
NPO2884 Annona squamosa Species Annonaceae Eukaryota n.a. n.a. n.a. PMID[19296389]
NPO2884 Annona squamosa Species Annonaceae Eukaryota n.a. n.a. n.a. PMID[21910504]
NPO2884 Annona squamosa Species Annonaceae Eukaryota seeds n.a. n.a. PMID[22011319]
NPO2884 Annona squamosa Species Annonaceae Eukaryota n.a. seed n.a. PMID[22011319]
NPO1099 Capparis spinosa Species Capparaceae Eukaryota aerial parts and buds Cagliari, Sardinia 2012-FEB PMID[22769561]
NPO2884 Annona squamosa Species Annonaceae Eukaryota Barks n.a. n.a. PMID[2348205]
NPO2884 Annona squamosa Species Annonaceae Eukaryota n.a. fruit n.a. PMID[8786370]
NPO2884 Annona squamosa Species Annonaceae Eukaryota bark n.a. n.a. PMID[9214729]
NPO25677 Xylopia parviflora Species Annonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2884 Annona squamosa Species Annonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1099 Capparis spinosa Species Capparaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1099 Capparis spinosa Species Capparaceae Eukaryota n.a. n.a. Database[FooDB]
NPO1099 Capparis spinosa Species Capparaceae Eukaryota Seed n.a. n.a. Database[FooDB]
NPO2884 Annona squamosa Species Annonaceae Eukaryota n.a. n.a. Database[FooDB]
NPO1099 Capparis spinosa Species Capparaceae Eukaryota n.a. n.a. Database[FooDB]
NPO1099 Capparis spinosa Species Capparaceae Eukaryota Leaf n.a. n.a. Database[FooDB]
NPO1099 Capparis spinosa Species Capparaceae Eukaryota Flower n.a. n.a. Database[FooDB]
NPO1099 Capparis spinosa Species Capparaceae Eukaryota Fruit n.a. n.a. Database[FooDB]
NPO2884 Annona squamosa Species Annonaceae Eukaryota Fruit n.a. n.a. Database[FooDB]
NPO1099 Capparis spinosa Species Capparaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO2884 Annona squamosa Species Annonaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO25677 Xylopia parviflora Species Annonaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO1099 Capparis spinosa Species Capparaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO2884 Annona squamosa Species Annonaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO1099 Capparis spinosa Species Capparaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO2884 Annona squamosa Species Annonaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO25677 Xylopia parviflora Species Annonaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2884 Annona squamosa 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

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 NPC535693 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 NPC314682
0.8444 Intermediate Similarity NPC213206
0.8444 Intermediate Similarity NPC188163
0.8444 Intermediate Similarity NPC328750
0.7551 Intermediate Similarity NPC185838
0.7451 Intermediate Similarity NPC135538
0.7451 Intermediate Similarity NPC24233
0.7358 Intermediate Similarity NPC247639
0.7358 Intermediate Similarity NPC25084
0.6949 Remote Similarity NPC256012
0.6949 Remote Similarity NPC610965
0.6724 Remote Similarity NPC317272
0.6724 Remote Similarity NPC268503
0.6119 Remote Similarity NPC600054
0.6119 Remote Similarity NPC601504
0.6111 Remote Similarity NPC609731
0.6094 Remote Similarity NPC603603
0.6 Remote Similarity NPC240841
0.6 Remote Similarity NPC147390
0.6 Remote Similarity NPC428
0.5938 Remote Similarity NPC276890
0.5926 Remote Similarity NPC474915
0.5893 Remote Similarity NPC317439
0.5862 Remote Similarity NPC27887
0.5781 Remote Similarity NPC76682
0.5781 Remote Similarity NPC10908
0.5781 Remote Similarity NPC63646
0.5781 Remote Similarity NPC317145
0.5781 Remote Similarity NPC198498
0.5781 Remote Similarity NPC115284
0.5714 Remote Similarity NPC191376
0.5652 Remote Similarity NPC112248
0.5614 Remote Similarity NPC321505
0.5614 Remote Similarity NPC179825
0.5571 Remote Similarity NPC601503
0.5522 Remote Similarity NPC12424
0.5522 Remote Similarity NPC129518
0.5522 Remote Similarity NPC251580
0.5479 Remote Similarity NPC601489
0.5479 Remote Similarity NPC604804
0.5441 Remote Similarity NPC603853
0.5429 Remote Similarity NPC475393
0.5405 Remote Similarity NPC605743
0.5373 Remote Similarity NPC227060
0.5362 Remote Similarity NPC290582
0.5362 Remote Similarity NPC217748
0.5362 Remote Similarity NPC73492
0.5362 Remote Similarity NPC182052
0.5362 Remote Similarity NPC271013
0.5362 Remote Similarity NPC299990
0.5362 Remote Similarity NPC42663
0.5362 Remote Similarity NPC15414
0.5362 Remote Similarity NPC480587
0.5342 Remote Similarity NPC302275
0.5333 Remote Similarity NPC475959
0.5286 Remote Similarity NPC279228
0.5283 Remote Similarity NPC128019
0.5263 Remote Similarity NPC210437
0.5263 Remote Similarity NPC16107
0.5263 Remote Similarity NPC106295
0.5211 Remote Similarity NPC311973
0.5211 Remote Similarity NPC239824
0.5211 Remote Similarity NPC600872
0.5172 Remote Similarity NPC51957
0.5139 Remote Similarity NPC185639
0.5139 Remote Similarity NPC251735
0.5139 Remote Similarity NPC116465
0.5139 Remote Similarity NPC49075
0.5139 Remote Similarity NPC223690
0.5139 Remote Similarity NPC9532
0.5139 Remote Similarity NPC599951
0.5102 Remote Similarity NPC470926
0.5082 Remote Similarity NPC104196
0.5077 Remote Similarity NPC30779
0.5075 Remote Similarity NPC480592
0.5072 Remote Similarity NPC610959
0.5068 Remote Similarity NPC274716
0.5068 Remote Similarity NPC167116
0.5068 Remote Similarity NPC609821

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC535693 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
0.8444 Intermediate Similarity NPD4664 Clinical (unspecified phase)
0.5781 Remote Similarity NPD8099 Discontinued
0.5441 Remote Similarity NPD8156 Discontinued
0.5362 Remote Similarity NPD8095 Phase 1
0.5345 Remote Similarity NPD4017 Phase 4
0.5263 Remote Similarity NPD4584 Phase 2

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