Natural Product: NPC188163

Natural Product IDNPC188163
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (1S)-1-[(3,4-Dimethoxyphenyl)Methyl]-6,7-Dimethoxy-2-Methyl-3,4-Dihydro-1H-Isoquinoline
IUPAC Name (1S)-1-[(3,4-dimethoxyphenyl)methyl]-6,7-dimethoxy-2-methyl-3,4-dihydro-1H-isoquinoline
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL519894
PubChem CID 73397
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0002566] Isoquinolines and derivatives
        • [CHEMONTID:0000054] Benzylisoquinolines

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 KGPAYJZAMGEDIQ-KRWDZBQOSA-N
Standard InCHI InChI=1S/C21H27NO4/c1-22-9-8-15-12-20(25-4)21(26-5)13-16(15)17(22)10-14-6-7-18(23-2)19(11-14)24-3/h6-7,11-13,17H,8-10H2,1-5H3/t17-/m0/s1
SMILES COc1cc(ccc1OC)C[C@@H]1N(C)CCc2c1cc(OC)c(c2)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   357.19 Volume:   376.442
?
Van der Waals volume.
Dense:   0.949 LogP:   2.284
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.575
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.35
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   17.0
TPSA:   40.16
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   0.0 Rings:   3.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.791 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.583 Fsp3:   0.429
MCE-18:   57.6
?
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:   0.245 Fluc inhibitor:   0.049
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.4
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.349
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.004 Promiscuous compounds:   0.588

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.516 MDCK Permeability:   -4.587
Pgp-inhibitor:   0.988 Pgp-substrate:   0.262
PAMPA:   0.002
?
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):   0.014
20% Bioavailability (F20%):   0.422 30% Bioavailability (F30%):   0.068
50% Bioavailability (F50%):   0.837

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.356 MRP1:   0.933
Plasma Protein Binding (PPB):   51.14% Volume Distribution (VD):   0.227
Fu: 42.56%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.979
OATP1B3 inhibitor:   0.972 BCRP inhibitor:   0.886
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.001
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.998 CYP2C9-substrate:   0.517
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.901
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   0.001
CYP2B6-substrate:   0.993 CYP2C8-inhibitor:   0.845
HLM stability:   0.905
?
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):  9.29 Half-life (T1/2):  3.045

ADMET: Toxicity

hERG Blockers:  0.439 hERG Blockers (10um):  0.588
Human Hepatotoxicity (H-HT):  0.735 Drug-induced Liver Injury (DILI):  0.195
AMES Toxicity:  0.537 Rat Oral Acute Toxicity:  0.313
Maximum Recommended Daily Dose:  0.769 Skin Sensitization:  0.505
Carcinogencity:  0.574 Eye Corrosion:  0.01
Eye Irritation:  0.645 Respiratory Toxicity:  0.608
Drug-induced Neurotoxicity:  0.885 Ototoxicity:  0.602
Hematotoxicity:  0.272 Drug-induced Nephrotoxicity:  0.279
Genotoxicity:  0.408 RPMI-8226 Immunitoxicity:  0.063
A549 Cytotoxicity:  0.069 Hek293 Cytotoxicity:  0.399
BCF:   1.974
?
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:   3.871
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.3
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.433
?
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
NPO9498 Papaver somniferum Species Papaveraceae Eukaryota n.a. n.a. n.a. DOI[10.1042/BA20020118]
NPO9498 Papaver somniferum Species Papaveraceae Eukaryota n.a. n.a. n.a. DOI[10.1556/abot.45.2003.3-4.15]
NPO9498 Papaver somniferum Species Papaveraceae Eukaryota n.a. n.a. n.a. PMID[15019787]
NPO21782 Nuxia sphaerocephala Species Stilbaceae Eukaryota leaves n.a. n.a. PMID[19299148]
NPO9498 Papaver somniferum Species Papaveraceae Eukaryota n.a. n.a. n.a. PMID[22029392]
NPO9498 Papaver somniferum Species Papaveraceae Eukaryota n.a. n.a. n.a. PMID[23517479]
NPO9498 Papaver somniferum Species Papaveraceae Eukaryota n.a. n.a. n.a. PMID[37685099]
NPO260 Cyclacanthia bellae Species Latrunculiidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21782 Nuxia sphaerocephala Species Stilbaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20090 Dalbergia spruceana Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10176 Chrozophora prostrata Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7312 Aplidium multiplicatum Species Polyclinidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2466 Aloe microstigma Species Asphodelaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9498 Papaver somniferum Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9498 Papaver somniferum Species Papaveraceae Eukaryota n.a. n.a. Database[FooDB]
NPO9498 Papaver somniferum Species Papaveraceae Eukaryota n.a. n.a. Database[FooDB]
NPO9498 Papaver somniferum Species Papaveraceae Eukaryota Seed n.a. n.a. Database[FooDB]
NPO9498 Papaver somniferum Species Papaveraceae Eukaryota Latex Exudate n.a. n.a. Database[FooDB]
NPO9498 Papaver somniferum Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO20090 Dalbergia spruceana Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO13887 Erythrophleum suaveolens Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO21782 Nuxia sphaerocephala Species Stilbaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO20090 Dalbergia spruceana Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO9498 Papaver somniferum Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO13887 Erythrophleum suaveolens Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO21782 Nuxia sphaerocephala Species Stilbaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO20090 Dalbergia spruceana Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO13887 Erythrophleum suaveolens Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO9498 Papaver somniferum Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO9498 Papaver somniferum Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO13887 Erythrophleum suaveolens Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21782 Nuxia sphaerocephala Species Stilbaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20090 Dalbergia spruceana Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23007 Horsfieldia glabra Species Myristicaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9498 Papaver somniferum Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO260 Cyclacanthia bellae Species Latrunculiidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19966 Dendrobium amplum Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10176 Chrozophora prostrata Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17383 Cyperus nipponicus Species Cyperaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2466 Aloe microstigma Species Asphodelaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7312 Aplidium multiplicatum Species Polyclinidae 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
NPT110 Individual protein Cytochrome P450 2D6 Homo sapiens Potency = 6309.6 nM PubChem BioAssay data set
NPT110 Individual protein Cytochrome P450 2D6 Homo sapiens Potency = 12589.3 nM PubChem BioAssay data set
NPT110 Individual protein Cytochrome P450 2D6 Homo sapiens AC50 = 6309.57 nM PubChem BioAssay data set
NPT483 Individual protein Prelamin-A/C Homo sapiens Potency = 316.2 nM PubChem BioAssay data set
NPT444 Individual protein Ubiquitin carboxyl-terminal hydrolase 1 Homo sapiens Potency n.a. 15848.9 nM PubChem BioAssay data set
NPT443 Individual protein Histone acetyltransferase GCN5 Homo sapiens Potency n.a. 8912.5 nM PubChem BioAssay data set

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT28438 Unchecked Unchecked n.a. IC50 n.a. n.a. n.a. PMID[33158578]

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 NPC188163 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 NPC213206
1.0 High Similarity NPC328750
0.8444 Intermediate Similarity NPC314682
0.7547 Intermediate Similarity NPC247639
0.7547 Intermediate Similarity NPC25084
0.7308 Intermediate Similarity NPC135538
0.7308 Intermediate Similarity NPC24233
0.7059 Intermediate Similarity NPC185838
0.6731 Remote Similarity NPC474915
0.661 Remote Similarity NPC317272
0.661 Remote Similarity NPC268503
0.629 Remote Similarity NPC256012
0.629 Remote Similarity NPC610965
0.625 Remote Similarity NPC603603
0.6094 Remote Similarity NPC276890
0.6034 Remote Similarity NPC27887
0.5938 Remote Similarity NPC76682
0.5938 Remote Similarity NPC10908
0.5938 Remote Similarity NPC63646
0.5938 Remote Similarity NPC317145
0.5938 Remote Similarity NPC198498
0.5938 Remote Similarity NPC115284
0.5909 Remote Similarity NPC240841
0.5893 Remote Similarity NPC147390
0.5893 Remote Similarity NPC428
0.5797 Remote Similarity NPC475393
0.5763 Remote Similarity NPC475959
0.5672 Remote Similarity NPC12424
0.5672 Remote Similarity NPC129518
0.5672 Remote Similarity NPC251580
0.5588 Remote Similarity NPC603853
0.5522 Remote Similarity NPC227060
0.5517 Remote Similarity NPC317439
0.5507 Remote Similarity NPC290582
0.5507 Remote Similarity NPC217748
0.5507 Remote Similarity NPC73492
0.5507 Remote Similarity NPC182052
0.5507 Remote Similarity NPC271013
0.5507 Remote Similarity NPC299990
0.5507 Remote Similarity NPC42663
0.5507 Remote Similarity NPC15414
0.5507 Remote Similarity NPC480587
0.5455 Remote Similarity NPC480592
0.5439 Remote Similarity NPC210437
0.5439 Remote Similarity NPC16107
0.5439 Remote Similarity NPC106295
0.5429 Remote Similarity NPC279228
0.5352 Remote Similarity NPC311973
0.5352 Remote Similarity NPC239824
0.5352 Remote Similarity NPC112248
0.5352 Remote Similarity NPC600054
0.5352 Remote Similarity NPC601504
0.5345 Remote Similarity NPC191376
0.5345 Remote Similarity NPC51957
0.5278 Remote Similarity NPC116465
0.5278 Remote Similarity NPC601503
0.5254 Remote Similarity NPC321505
0.5254 Remote Similarity NPC179825
0.5231 Remote Similarity NPC30779
0.5185 Remote Similarity NPC128019
0.5172 Remote Similarity NPC609731
0.5139 Remote Similarity NPC286119
0.5139 Remote Similarity NPC600872
0.5077 Remote Similarity NPC226708
0.5068 Remote Similarity NPC185639
0.5068 Remote Similarity NPC251735
0.5068 Remote Similarity NPC254441
0.5068 Remote Similarity NPC49075
0.5068 Remote Similarity NPC223690
0.5068 Remote Similarity NPC9532
0.5068 Remote Similarity NPC599951
0.5067 Remote Similarity NPC302275
0.5067 Remote Similarity NPC195538

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC188163 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
1.0 High Similarity NPD4664 Clinical (unspecified phase)
0.5938 Remote Similarity NPD8099 Discontinued
0.5588 Remote Similarity NPD8156 Discontinued
0.5507 Remote Similarity NPD8095 Phase 1
0.5439 Remote Similarity NPD4584 Phase 2
0.5254 Remote Similarity NPD4017 Phase 4

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