Structure

Physi-Chem Properties

Molecular Weight:  245.07
Volume:  238.074
LogP:  2.556
LogD:  2.837
LogS:  -3.298
# Rotatable Bonds:  2
TPSA:  64.72
# H-Bond Aceptor:  5
# H-Bond Donor:  1
# Rings:  3
# Heavy Atoms:  5

MedChem Properties

QED Drug-Likeness Score:  0.752
Synthetic Accessibility Score:  2.74
Fsp3:  0.154
Lipinski Rule-of-5:  Accepted
Pfizer Rule:  Accepted
GSK Rule:  Accepted
BMS Rule:  0
Golden Triangle Rule:  Accepted
Chelating Alert:  1
PAINS Alert:  0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:  -4.855
MDCK Permeability:  2.5915291189448908e-05
Pgp-inhibitor:  0.002
Pgp-substrate:  0.001
Human Intestinal Absorption (HIA):  0.023
20% Bioavailability (F20%):  0.002
30% Bioavailability (F30%):  0.001

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):  0.033
Plasma Protein Binding (PPB):  93.19465637207031%
Volume Distribution (VD):  0.435
Pgp-substrate:  6.456506252288818%

ADMET: Metabolism

CYP1A2-inhibitor:  0.976
CYP1A2-substrate:  0.95
CYP2C19-inhibitor:  0.675
CYP2C19-substrate:  0.454
CYP2C9-inhibitor:  0.595
CYP2C9-substrate:  0.817
CYP2D6-inhibitor:  0.718
CYP2D6-substrate:  0.869
CYP3A4-inhibitor:  0.714
CYP3A4-substrate:  0.351

ADMET: Excretion

Clearance (CL):  11.219
Half-life (T1/2):  0.72

ADMET: Toxicity

hERG Blockers:  0.037
Human Hepatotoxicity (H-HT):  0.134
Drug-inuced Liver Injury (DILI):  0.942
AMES Toxicity:  0.459
Rat Oral Acute Toxicity:  0.734
Maximum Recommended Daily Dose:  0.052
Skin Sensitization:  0.618
Carcinogencity:  0.76
Eye Corrosion:  0.003
Eye Irritation:  0.254
Respiratory Toxicity:  0.928

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Data Type Select
General Info & Identifiers & Properties  
Structure MOL file  
Source Organisms  
Biological Activities  
Similar NPs/Drugs  

  Natural Product: NPC286692

Natural Product ID:  NPC286692
Common Name*:   Haplopine
IUPAC Name:   4,8-dimethoxy-9H-furo[2,3-b]quinolin-7-one
Synonyms:  
Standard InCHIKey:  WXPKAFIGBNLGNT-UHFFFAOYSA-N
Standard InCHI:  InChI=1S/C13H11NO4/c1-16-11-7-3-4-9(15)12(17-2)10(7)14-13-8(11)5-6-18-13/h3-6,14H,1-2H3
SMILES:  COc1c2-c(c(c(=O)cc2)OC)[nH]c2c1cco2
Synthetic Gene Cluster:   n.a.
ChEMBL Identifier:   CHEMBL400257
PubChem CID:   165368
Chemical Classification**:  
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0001253] Quinolines and derivatives
        • [CHEMONTID:0002374] Furanoquinolines

*Note: the InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
**Note: the Chemical Classification was calculated by NPClassifier Version 1.5. Reference: PMID:34662515.

  Species Source

Organism ID Organism Name Taxonomy Level Family SuperKingdom Isolation Part Collection Location Collection Time Reference
NPO20244 Melicope semecarpifolia Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[11575945]
NPO20244 Melicope semecarpifolia Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[18163582]
NPO5315 Zanthoxylum bungeanum Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[24175626]
NPO14991 Zanthoxylum cuspidatum Species Rutaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO28560 Sarcomelicope glauca Species Rutaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO5315 Zanthoxylum bungeanum Species Rutaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO1002 Haplophyllum perforatum Species Rutaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO20244 Melicope semecarpifolia Species Rutaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO20244 Melicope semecarpifolia Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO28560 Sarcomelicope glauca Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO14991 Zanthoxylum cuspidatum Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO5315 Zanthoxylum bungeanum Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO1002 Haplophyllum perforatum Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO5315 Zanthoxylum bungeanum Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO14991 Zanthoxylum cuspidatum Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO5315 Zanthoxylum bungeanum Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO28560 Sarcomelicope glauca Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5315 Zanthoxylum bungeanum Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20244 Melicope semecarpifolia Species Rutaceae 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 NP ID 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

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT204 Individual Protein Acetylcholinesterase Homo sapiens IC50 > 100.0 ug.mL-1 PMID[575707]
NPT204 Individual Protein Acetylcholinesterase Homo sapiens Inhibition = 51.9 % PMID[575707]

☑ Note for Activity Records:
☉ The quantitative biological activities were primarily integrated from ChEMBL (Version-30) database and were also directly collected from PubMed literature. PubMed PMID was provided as the reference link for each activity record.

  Chemically structural similarity: I. Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes 4,3285 NPs with experimentally-derived bioactivity available in NPASS)

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules. Tc lies between [0, 1] where '1' indicates the highest similarity. What is Tanimoto coefficient

●  The left chart: Distribution of similarity level between NPC286692 and all remaining natural products in the NPASS database.
●  The right table: Most similar natural products (Tc>=0.56 or Top200).

Similarity Score Similarity Level Natural Product ID
0.7289 Intermediate Similarity NPC471652
0.6959 Remote Similarity NPC471648
0.6612 Remote Similarity NPC45389
0.6585 Remote Similarity NPC471646
0.6585 Remote Similarity NPC471647
0.6374 Remote Similarity NPC471649
0.6368 Remote Similarity NPC112937
0.6289 Remote Similarity NPC41216
0.6181 Remote Similarity NPC269367
0.618 Remote Similarity NPC471651
0.6059 Remote Similarity NPC16066
0.6048 Remote Similarity NPC325857
0.6045 Remote Similarity NPC257763
0.5971 Remote Similarity NPC131885
0.5942 Remote Similarity NPC298436
0.5935 Remote Similarity NPC244862
0.5935 Remote Similarity NPC67345
0.5932 Remote Similarity NPC301163
0.5921 Remote Similarity NPC292036
0.5902 Remote Similarity NPC73280
0.5899 Remote Similarity NPC93653
0.5882 Remote Similarity NPC472163
0.5868 Remote Similarity NPC216149
0.5868 Remote Similarity NPC208170
0.5846 Remote Similarity NPC308895
0.5829 Remote Similarity NPC205372
0.5823 Remote Similarity NPC270807
0.5823 Remote Similarity NPC174915
0.5822 Remote Similarity NPC140296
0.5821 Remote Similarity NPC477161
0.5802 Remote Similarity NPC97746
0.5798 Remote Similarity NPC197335
0.5784 Remote Similarity NPC25961
0.5772 Remote Similarity NPC140688
0.5767 Remote Similarity NPC314659
0.5759 Remote Similarity NPC262725
0.5759 Remote Similarity NPC87391
0.5747 Remote Similarity NPC223873
0.5741 Remote Similarity NPC217176
0.574 Remote Similarity NPC471653
0.5714 Remote Similarity NPC299582
0.5706 Remote Similarity NPC474722
0.5704 Remote Similarity NPC265461
0.5699 Remote Similarity NPC471650
0.568 Remote Similarity NPC476475
0.5678 Remote Similarity NPC241263
0.5673 Remote Similarity NPC476462
0.5671 Remote Similarity NPC208389
0.5669 Remote Similarity NPC87466
0.5662 Remote Similarity NPC34770
0.5661 Remote Similarity NPC283810
0.566 Remote Similarity NPC1848
0.561 Remote Similarity NPC26532
0.5607 Remote Similarity NPC260601
0.5605 Remote Similarity NPC217180
0.5605 Remote Similarity NPC312525

  Chemically structural similarity: II. Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC286692 and all drugs/candidates.
●  The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

Similarity Score Similarity Level Drug ID Developmental Stage
0.6258 Remote Similarity NPD822 Approved
0.6243 Remote Similarity NPD1212 Approved
0.601 Remote Similarity NPD7880 Clinical (unspecified phase)
0.6 Remote Similarity NPD1880 Phase 3
0.5771 Remote Similarity NPD4465 Phase 2
0.5771 Remote Similarity NPD4467 Phase 2
0.5767 Remote Similarity NPD3253 Clinical (unspecified phase)
0.5749 Remote Similarity NPD4679 Discontinued
0.5707 Remote Similarity NPD5186 Approved
0.5707 Remote Similarity NPD5183 Approved
0.5681 Remote Similarity NPD7547 Clinical (unspecified phase)
0.5678 Remote Similarity NPD2778 Approved
0.5657 Remote Similarity NPD5515 Phase 2
0.5642 Remote Similarity NPD2366 Approved
0.5638 Remote Similarity NPD5521 Clinical (unspecified phase)
0.5625 Remote Similarity NPD6021 Clinical (unspecified phase)
0.5622 Remote Similarity NPD6321 Discontinued
0.5619 Remote Similarity NPD2542 Clinical (unspecified phase)
0.5608 Remote Similarity NPD5900 Clinical (unspecified phase)
0.5607 Remote Similarity NPD2241 Approved
0.5606 Remote Similarity NPD3964 Approved

  Bioactivity similarity: Similar Natural Products in NPASS

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