Structure

Physi-Chem Properties

Molecular Weight:  144.04
Volume:  139.584
LogP:  0.53
LogD:  0.51
LogS:  -1.287
# Rotatable Bonds:  4
TPSA:  63.6
# H-Bond Aceptor:  4
# H-Bond Donor:  1
# Rings:  0
# Heavy Atoms:  4

MedChem Properties

QED Drug-Likeness Score:  0.453
Synthetic Accessibility Score:  2.041
Fsp3:  0.333
Lipinski Rule-of-5:  Accepted
Pfizer Rule:  Accepted
GSK Rule:  Accepted
BMS Rule:  0
Golden Triangle Rule:  Rejected
Chelating Alert:  0
PAINS Alert:  0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:  -4.942
MDCK Permeability:  4.455810631043278e-05
Pgp-inhibitor:  0.0
Pgp-substrate:  0.006
Human Intestinal Absorption (HIA):  0.008
20% Bioavailability (F20%):  0.006
30% Bioavailability (F30%):  0.991

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):  0.206
Plasma Protein Binding (PPB):  42.14399719238281%
Volume Distribution (VD):  0.289
Pgp-substrate:  44.523765563964844%

ADMET: Metabolism

CYP1A2-inhibitor:  0.089
CYP1A2-substrate:  0.08
CYP2C19-inhibitor:  0.049
CYP2C19-substrate:  0.054
CYP2C9-inhibitor:  0.042
CYP2C9-substrate:  0.933
CYP2D6-inhibitor:  0.066
CYP2D6-substrate:  0.201
CYP3A4-inhibitor:  0.024
CYP3A4-substrate:  0.057

ADMET: Excretion

Clearance (CL):  5.58
Half-life (T1/2):  0.893

ADMET: Toxicity

hERG Blockers:  0.002
Human Hepatotoxicity (H-HT):  0.205
Drug-inuced Liver Injury (DILI):  0.445
AMES Toxicity:  0.029
Rat Oral Acute Toxicity:  0.036
Maximum Recommended Daily Dose:  0.007
Skin Sensitization:  0.925
Carcinogencity:  0.094
Eye Corrosion:  0.984
Eye Irritation:  0.986
Respiratory Toxicity:  0.158

Download Data

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

  Natural Product: NPC41409

Natural Product ID:  NPC41409
Common Name*:   Ethyl Fumarate
IUPAC Name:   (E)-4-ethoxy-4-oxobut-2-enoic acid
Synonyms:   Ethyl Fumarate
Standard InCHIKey:  XLYMOEINVGRTEX-ONEGZZNKSA-N
Standard InCHI:  InChI=1S/C6H8O4/c1-2-10-6(9)4-3-5(7)8/h3-4H,2H2,1H3,(H,7,8)/b4-3+
SMILES:  CCOC(=O)/C=C/C(=O)O
Synthetic Gene Cluster:   n.a.
ChEMBL Identifier:   CHEMBL1771637
PubChem CID:   5358902
Chemical Classification**:  
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0003909] Fatty Acyls
        • [CHEMONTID:0000324] Fatty acid esters

*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
NPO3578 Andrographis paniculata Species Acanthaceae Eukaryota n.a. leaf n.a. PMID[15894448]
NPO3578 Andrographis paniculata Species Acanthaceae Eukaryota n.a. root n.a. PMID[15894448]
NPO3578 Andrographis paniculata Species Acanthaceae Eukaryota aerial parts purchased in Juhuacun herbal market, Kunming, Yunnan Province, China 2002-Oct PMID[16562826]
NPO3578 Andrographis paniculata Species Acanthaceae Eukaryota n.a. n.a. n.a. PMID[18357994]
NPO3578 Andrographis paniculata Species Acanthaceae Eukaryota n.a. leaf n.a. PMID[21598983]
NPO3578 Andrographis paniculata Species Acanthaceae Eukaryota n.a. leaf n.a. PMID[22026410]
NPO3578 Andrographis paniculata Species Acanthaceae Eukaryota n.a. n.a. n.a. PMID[8377022]
NPO3578 Andrographis paniculata Species Acanthaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO25890 Herba cirsii japonici n.a. n.a. n.a. n.a. n.a. n.a. Database[TCMID]
NPO19689 Radix cirsii japonici Species Lymnaeidae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO3578 Andrographis paniculata Species Acanthaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO23795 Herba seu radix cirsii japonici n.a. n.a. n.a. n.a. n.a. n.a. Database[TCMID]
NPO3876 Andrographis elongata Species Acanthaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO3578 Andrographis paniculata Species Acanthaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO16865.1 Prunus serrulata var. spontanea Varieties Rosaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO3578 Andrographis paniculata Species Acanthaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO3876 Andrographis elongata Species Acanthaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3578 Andrographis paniculata Species Acanthaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16865.1 Prunus serrulata var. spontanea Varieties Rosaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16885 Phonus arborescens Species Asteraceae 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
NPT525 Individual Protein Hydroxycarboxylic acid receptor 2 Homo sapiens Ki = 410.0 nM PMID[482709]
NPT2 Others Unspecified Ki = 52400.0 nM PMID[482710]
NPT2 Others Unspecified Activity = 45.6 % PMID[482710]
NPT2 Others Unspecified Ki = 888000.0 nM PMID[482710]
NPT2 Others Unspecified Ki = 59100.0 nM PMID[482710]

☑ 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 NPC41409 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
0.9231 High Similarity NPC298413
0.9 High Similarity NPC281043
0.8 Intermediate Similarity NPC65353
0.7949 Intermediate Similarity NPC98098
0.7949 Intermediate Similarity NPC224651
0.7857 Intermediate Similarity NPC147824
0.775 Intermediate Similarity NPC60675
0.775 Intermediate Similarity NPC297363
0.7674 Intermediate Similarity NPC250954
0.7674 Intermediate Similarity NPC297608
0.7674 Intermediate Similarity NPC203382
0.7619 Intermediate Similarity NPC63598
0.75 Intermediate Similarity NPC63354
0.7381 Intermediate Similarity NPC107877
0.7358 Intermediate Similarity NPC129150
0.7358 Intermediate Similarity NPC294938
0.7317 Intermediate Similarity NPC122676
0.7292 Intermediate Similarity NPC128520
0.7273 Intermediate Similarity NPC8270
0.7222 Intermediate Similarity NPC223679
0.7222 Intermediate Similarity NPC254095
0.7143 Intermediate Similarity NPC308418
0.7111 Intermediate Similarity NPC221250
0.7091 Intermediate Similarity NPC82465
0.7091 Intermediate Similarity NPC97570
0.7037 Intermediate Similarity NPC293437
0.7037 Intermediate Similarity NPC135863
0.7037 Intermediate Similarity NPC249850
0.7 Intermediate Similarity NPC15789
0.7 Intermediate Similarity NPC275316
0.6957 Remote Similarity NPC102879
0.6957 Remote Similarity NPC57923
0.6923 Remote Similarity NPC323552
0.6909 Remote Similarity NPC21946
0.6852 Remote Similarity NPC230296
0.6842 Remote Similarity NPC26810
0.68 Remote Similarity NPC126184
0.6786 Remote Similarity NPC302564
0.6739 Remote Similarity NPC159773
0.6667 Remote Similarity NPC20903
0.6667 Remote Similarity NPC236338
0.6667 Remote Similarity NPC130953
0.6667 Remote Similarity NPC98519
0.661 Remote Similarity NPC470808
0.6607 Remote Similarity NPC189700
0.66 Remote Similarity NPC90490
0.6545 Remote Similarity NPC51846
0.65 Remote Similarity NPC19769
0.65 Remote Similarity NPC96414
0.65 Remote Similarity NPC273600
0.6471 Remote Similarity NPC82446
0.6441 Remote Similarity NPC473737
0.6441 Remote Similarity NPC68110
0.6393 Remote Similarity NPC146811
0.6393 Remote Similarity NPC201356
0.6364 Remote Similarity NPC9290
0.6316 Remote Similarity NPC474084
0.6296 Remote Similarity NPC477780
0.6296 Remote Similarity NPC477781
0.629 Remote Similarity NPC122627
0.6271 Remote Similarity NPC263732
0.625 Remote Similarity NPC150717
0.6226 Remote Similarity NPC43053
0.62 Remote Similarity NPC47946
0.62 Remote Similarity NPC270706
0.62 Remote Similarity NPC26600
0.619 Remote Similarity NPC63873
0.6182 Remote Similarity NPC218486
0.6182 Remote Similarity NPC151761
0.6182 Remote Similarity NPC159535
0.6167 Remote Similarity NPC2328
0.614 Remote Similarity NPC265551
0.614 Remote Similarity NPC212730
0.6129 Remote Similarity NPC475675
0.6129 Remote Similarity NPC475555
0.6129 Remote Similarity NPC276299
0.6102 Remote Similarity NPC26223
0.6094 Remote Similarity NPC151481
0.6094 Remote Similarity NPC475982
0.6087 Remote Similarity NPC226511
0.6078 Remote Similarity NPC87137
0.6078 Remote Similarity NPC197467
0.6078 Remote Similarity NPC128280
0.6038 Remote Similarity NPC221467
0.6 Remote Similarity NPC304079
0.6 Remote Similarity NPC55376
0.6 Remote Similarity NPC476037
0.6 Remote Similarity NPC327103
0.6 Remote Similarity NPC51329
0.6 Remote Similarity NPC312547
0.6 Remote Similarity NPC6963
0.5968 Remote Similarity NPC470123
0.5968 Remote Similarity NPC282760
0.5965 Remote Similarity NPC245002
0.5965 Remote Similarity NPC472808
0.5965 Remote Similarity NPC324224
0.5965 Remote Similarity NPC221763
0.5932 Remote Similarity NPC22897
0.5932 Remote Similarity NPC86789
0.5932 Remote Similarity NPC159650
0.5909 Remote Similarity NPC316185
0.5909 Remote Similarity NPC217161
0.5909 Remote Similarity NPC293114
0.5902 Remote Similarity NPC475073
0.5902 Remote Similarity NPC474774
0.5893 Remote Similarity NPC478120
0.5882 Remote Similarity NPC172042
0.5849 Remote Similarity NPC135698
0.5849 Remote Similarity NPC234084
0.5833 Remote Similarity NPC123357
0.5833 Remote Similarity NPC79756
0.5833 Remote Similarity NPC471278
0.5833 Remote Similarity NPC309408
0.5821 Remote Similarity NPC284006
0.5821 Remote Similarity NPC329890
0.5818 Remote Similarity NPC106531
0.5818 Remote Similarity NPC191643
0.5806 Remote Similarity NPC25747
0.5806 Remote Similarity NPC148233
0.5806 Remote Similarity NPC308457
0.5789 Remote Similarity NPC474913
0.5781 Remote Similarity NPC132286
0.5769 Remote Similarity NPC308331
0.5758 Remote Similarity NPC59558
0.5758 Remote Similarity NPC202011
0.5758 Remote Similarity NPC476012
0.5735 Remote Similarity NPC315843
0.5714 Remote Similarity NPC478098
0.5714 Remote Similarity NPC8466
0.5714 Remote Similarity NPC478099
0.5692 Remote Similarity NPC238223
0.569 Remote Similarity NPC86948
0.5682 Remote Similarity NPC144407
0.5667 Remote Similarity NPC222852
0.566 Remote Similarity NPC68577
0.5652 Remote Similarity NPC260396
0.5645 Remote Similarity NPC179087
0.5645 Remote Similarity NPC44343
0.5645 Remote Similarity NPC210303
0.5641 Remote Similarity NPC110107
0.5625 Remote Similarity NPC124586
0.5625 Remote Similarity NPC37382
0.5625 Remote Similarity NPC470033
0.5614 Remote Similarity NPC269615
0.5614 Remote Similarity NPC135537
0.5614 Remote Similarity NPC474127
0.56 Remote Similarity NPC187922

  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 NPC41409 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
0.8718 High Similarity NPD9115 Approved
0.7949 Intermediate Similarity NPD8573 Approved
0.6667 Remote Similarity NPD8187 Phase 3
0.5952 Remote Similarity NPD9114 Clinical (unspecified phase)
0.5882 Remote Similarity NPD9378 Approved
0.5849 Remote Similarity NPD4220 Pre-registration
0.58 Remote Similarity NPD9411 Phase 1
0.5636 Remote Similarity NPD6927 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