Structure

Physi-Chem Properties

Molecular Weight:  247.08
Volume:  246.63
LogP:  1.03
LogD:  1.322
LogS:  -3.086
# Rotatable Bonds:  2
TPSA:  65.37
# H-Bond Aceptor:  5
# H-Bond Donor:  0
# Rings:  2
# Heavy Atoms:  5

MedChem Properties

QED Drug-Likeness Score:  0.784
Synthetic Accessibility Score:  2.711
Fsp3:  0.308
Lipinski Rule-of-5:  Accepted
Pfizer Rule:  Accepted
GSK Rule:  Accepted
BMS Rule:  0
Golden Triangle Rule:  Accepted
Chelating Alert:  0
PAINS Alert:  1

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:  -4.588
MDCK Permeability:  3.4630156733328477e-05
Pgp-inhibitor:  0.241
Pgp-substrate:  0.001
Human Intestinal Absorption (HIA):  0.003
20% Bioavailability (F20%):  0.858
30% Bioavailability (F30%):  0.241

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):  0.136
Plasma Protein Binding (PPB):  74.60308837890625%
Volume Distribution (VD):  1.323
Pgp-substrate:  19.725833892822266%

ADMET: Metabolism

CYP1A2-inhibitor:  0.972
CYP1A2-substrate:  0.886
CYP2C19-inhibitor:  0.492
CYP2C19-substrate:  0.215
CYP2C9-inhibitor:  0.341
CYP2C9-substrate:  0.229
CYP2D6-inhibitor:  0.243
CYP2D6-substrate:  0.11
CYP3A4-inhibitor:  0.063
CYP3A4-substrate:  0.17

ADMET: Excretion

Clearance (CL):  4.641
Half-life (T1/2):  0.214

ADMET: Toxicity

hERG Blockers:  0.015
Human Hepatotoxicity (H-HT):  0.075
Drug-inuced Liver Injury (DILI):  0.287
AMES Toxicity:  0.885
Rat Oral Acute Toxicity:  0.089
Maximum Recommended Daily Dose:  0.585
Skin Sensitization:  0.076
Carcinogencity:  0.134
Eye Corrosion:  0.003
Eye Irritation:  0.295
Respiratory Toxicity:  0.052

Download Data

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

  Natural Product: NPC2640

Natural Product ID:  NPC2640
Common Name*:   Cribrostatin 2
IUPAC Name:   7-ethoxy-2,6-dimethylisoquinoline-3,5,8-trione
Synonyms:   Cribrostatin 2
Standard InCHIKey:  BUJWDBKNRAIPLZ-UHFFFAOYSA-N
Standard InCHI:  InChI=1S/C13H13NO4/c1-4-18-13-7(2)11(16)8-5-10(15)14(3)6-9(8)12(13)17/h5-6H,4H2,1-3H3
SMILES:  CCOC1=C(C)C(=O)c2c(C1=O)cn(c(=O)c2)C
Synthetic Gene Cluster:   n.a.
ChEMBL Identifier:   CHEMBL494048
PubChem CID:   9825044
Chemical Classification**:  
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0002566] Isoquinolines and derivatives
        • [CHEMONTID:0002567] Isoquinoline quinones

*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
NPO33225 cribrochalina sp. Species Niphatidae Eukaryota n.a. republic of maldives n.a. PMID[10869203]
NPO33225 cribrochalina sp. Species Niphatidae Eukaryota n.a. n.a. n.a. PMID[12713412]

☑ 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
NPT1522 Organism Neisseria gonorrhoeae Neisseria gonorrhoeae MIC = 0.39 ug PMID[449400]
NPT1118 Organism Streptococcus pneumoniae Streptococcus pneumoniae MIC = 50.0 ug PMID[449400]
NPT1118 Organism Streptococcus pneumoniae Streptococcus pneumoniae MIC = 25.0 ug PMID[449400]
NPT1118 Organism Streptococcus pneumoniae Streptococcus pneumoniae MIC = 12.5 ug PMID[449400]
NPT79 Organism Bacillus subtilis Bacillus subtilis MIC = 25.0 ug PMID[449400]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC = 12.5 ug PMID[449400]
NPT729 Organism Micrococcus luteus Micrococcus luteus MIC = 50.0 ug PMID[449400]
NPT85 Organism Filobasidiella neoformans Cryptococcus neoformans MIC = 12.5 ug PMID[449400]
NPT20 Organism Candida albicans Candida albicans MIC = 3.12 ug PMID[449400]

☑ 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 NPC2640 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
0.9036 High Similarity NPC475614
0.6835 Remote Similarity NPC139056
0.675 Remote Similarity NPC473494
0.6628 Remote Similarity NPC94488
0.6512 Remote Similarity NPC134385
0.6506 Remote Similarity NPC151728
0.6506 Remote Similarity NPC57463
0.6442 Remote Similarity NPC316730
0.6429 Remote Similarity NPC34622
0.6429 Remote Similarity NPC474400
0.6395 Remote Similarity NPC474619
0.6395 Remote Similarity NPC243272
0.6383 Remote Similarity NPC312419
0.6353 Remote Similarity NPC98897
0.6322 Remote Similarity NPC263382
0.6322 Remote Similarity NPC146376
0.6322 Remote Similarity NPC125578
0.6279 Remote Similarity NPC16119
0.625 Remote Similarity NPC262673
0.6237 Remote Similarity NPC28529
0.622 Remote Similarity NPC320421
0.6204 Remote Similarity NPC9436
0.618 Remote Similarity NPC291062
0.618 Remote Similarity NPC94743
0.6154 Remote Similarity NPC264178
0.6111 Remote Similarity NPC318544
0.6061 Remote Similarity NPC472136
0.6061 Remote Similarity NPC472161
0.6055 Remote Similarity NPC470073
0.6036 Remote Similarity NPC470072
0.6023 Remote Similarity NPC251429
0.6023 Remote Similarity NPC298249
0.602 Remote Similarity NPC469884
0.6018 Remote Similarity NPC44733
0.6017 Remote Similarity NPC477140
0.6017 Remote Similarity NPC477143
0.6 Remote Similarity NPC474805
0.596 Remote Similarity NPC470177
0.596 Remote Similarity NPC296589
0.5957 Remote Similarity NPC283087
0.5957 Remote Similarity NPC473536
0.5941 Remote Similarity NPC116231
0.5934 Remote Similarity NPC133098
0.593 Remote Similarity NPC143168
0.593 Remote Similarity NPC53109
0.5926 Remote Similarity NPC317796
0.5922 Remote Similarity NPC32944
0.5922 Remote Similarity NPC193396
0.5882 Remote Similarity NPC95364
0.5882 Remote Similarity NPC142159
0.5877 Remote Similarity NPC475608
0.5877 Remote Similarity NPC21713
0.5862 Remote Similarity NPC7029
0.5841 Remote Similarity NPC21324
0.5814 Remote Similarity NPC68044
0.58 Remote Similarity NPC281172
0.5794 Remote Similarity NPC472167
0.5794 Remote Similarity NPC472166
0.5769 Remote Similarity NPC166110
0.5758 Remote Similarity NPC288281
0.5755 Remote Similarity NPC31021
0.575 Remote Similarity NPC22329
0.5747 Remote Similarity NPC477830
0.5743 Remote Similarity NPC203795
0.5732 Remote Similarity NPC129710
0.5728 Remote Similarity NPC81195
0.5714 Remote Similarity NPC224103
0.5714 Remote Similarity NPC299369
0.5714 Remote Similarity NPC477688
0.5714 Remote Similarity NPC248193
0.5714 Remote Similarity NPC200831
0.5701 Remote Similarity NPC318082
0.5673 Remote Similarity NPC223093
0.5673 Remote Similarity NPC53240
0.5673 Remote Similarity NPC224270
0.5657 Remote Similarity NPC47450
0.5648 Remote Similarity NPC472162
0.5648 Remote Similarity NPC265662
0.5648 Remote Similarity NPC241426
0.5644 Remote Similarity NPC133652
0.5636 Remote Similarity NPC469851
0.563 Remote Similarity NPC475642
0.5625 Remote Similarity NPC220191
0.5625 Remote Similarity NPC133420
0.5619 Remote Similarity NPC32552

  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 NPC2640 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
0.6383 Remote Similarity NPD5115 Clinical (unspecified phase)
0.6279 Remote Similarity NPD6108 Clinical (unspecified phase)
0.6129 Remote Similarity NPD4756 Discovery
0.6092 Remote Similarity NPD3704 Approved
0.593 Remote Similarity NPD2664 Clinical (unspecified phase)
0.5914 Remote Similarity NPD1452 Discontinued
0.5714 Remote Similarity NPD8779 Phase 3

  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