Structure

Physi-Chem Properties

Molecular Weight:  130.03
Volume:  122.288
LogP:  0.028
LogD:  0.602
LogS:  -1.022
# Rotatable Bonds:  3
TPSA:  63.6
# H-Bond Aceptor:  4
# H-Bond Donor:  1
# Rings:  0
# Heavy Atoms:  4

MedChem Properties

QED Drug-Likeness Score:  0.415
Synthetic Accessibility Score:  2.151
Fsp3:  0.2
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:  -5.017
MDCK Permeability:  5.718326065107249e-05
Pgp-inhibitor:  0.0
Pgp-substrate:  0.016
Human Intestinal Absorption (HIA):  0.096
20% Bioavailability (F20%):  0.008
30% Bioavailability (F30%):  0.991

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):  0.291
Plasma Protein Binding (PPB):  32.293331146240234%
Volume Distribution (VD):  0.284
Pgp-substrate:  47.65840530395508%

ADMET: Metabolism

CYP1A2-inhibitor:  0.027
CYP1A2-substrate:  0.121
CYP2C19-inhibitor:  0.044
CYP2C19-substrate:  0.053
CYP2C9-inhibitor:  0.025
CYP2C9-substrate:  0.928
CYP2D6-inhibitor:  0.138
CYP2D6-substrate:  0.215
CYP3A4-inhibitor:  0.017
CYP3A4-substrate:  0.036

ADMET: Excretion

Clearance (CL):  4.719
Half-life (T1/2):  0.907

ADMET: Toxicity

hERG Blockers:  0.002
Human Hepatotoxicity (H-HT):  0.607
Drug-inuced Liver Injury (DILI):  0.398
AMES Toxicity:  0.03
Rat Oral Acute Toxicity:  0.135
Maximum Recommended Daily Dose:  0.008
Skin Sensitization:  0.924
Carcinogencity:  0.05
Eye Corrosion:  0.977
Eye Irritation:  0.95
Respiratory Toxicity:  0.191

Download Data

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

  Natural Product: NPC298413

Natural Product ID:  NPC298413
Common Name*:   Methyl Fumarate
IUPAC Name:   (E)-4-methoxy-4-oxobut-2-enoic acid
Synonyms:   Methyl Fumarate
Standard InCHIKey:  NKHAVTQWNUWKEO-NSCUHMNNSA-N
Standard InCHI:  InChI=1S/C5H6O4/c1-9-5(8)3-2-4(6)7/h2-3H,1H3,(H,6,7)/b3-2+
SMILES:  COC(=O)/C=C/C(=O)O
Synthetic Gene Cluster:   n.a.
ChEMBL Identifier:   CHEMBL589586
PubChem CID:   5369209
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
NPO40434 Chaetomium nigricolor Species Chaetomiaceae Eukaryota n.a. n.a. n.a. PMID[32163284]
NPO8118 Pteris ensiformis Species Pteridaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12086 Rothmannia longiflora Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17466 Xestia c-nigrum Species 0ctuidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11263 Viburnum phlebotrichum Species Adoxaceae 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
NPT1144 Individual Protein Carbonic anhydrase VB Homo sapiens Kinact = 98.0 nM PMID[505274]
NPT1143 Individual Protein Carbonic anhydrase VA Homo sapiens Kinact = 103.0 nM PMID[505274]
NPT233 Individual Protein Carbonic anhydrase II Homo sapiens Kinact = 7.5 uM PMID[505274]
NPT525 Individual Protein Hydroxycarboxylic acid receptor 2 Homo sapiens Ki = 180.0 nM PMID[505275]
NPT2 Others Unspecified Selectivity ratio = 120.0 n.a. PMID[505274]
NPT947 Individual Protein Carbonic anhydrase I Homo sapiens Kinact = 284.0 uM PMID[505274]
NPT27 Others Unspecified PPB n.a. 86.05 % PMID[505277]
NPT20555 ORGANISM SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 IC50 > 20000.0 nM PMID[505279]
NPT20555 ORGANISM SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 IC50 > 19952.62 nM PMID[505279]

☑ 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 NPC298413 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 NPC41409
0.8611 High Similarity NPC98098
0.8611 High Similarity NPC224651
0.8378 Intermediate Similarity NPC60675
0.8378 Intermediate Similarity NPC297363
0.825 Intermediate Similarity NPC281043
0.7949 Intermediate Similarity NPC107877
0.7805 Intermediate Similarity NPC297608
0.7805 Intermediate Similarity NPC250954
0.775 Intermediate Similarity NPC63598
0.7561 Intermediate Similarity NPC147824
0.75 Intermediate Similarity NPC323552
0.7436 Intermediate Similarity NPC122676
0.7381 Intermediate Similarity NPC8270
0.725 Intermediate Similarity NPC65353
0.725 Intermediate Similarity NPC308418
0.7222 Intermediate Similarity NPC20903
0.7209 Intermediate Similarity NPC221250
0.7045 Intermediate Similarity NPC102879
0.7021 Intermediate Similarity NPC128520
0.6977 Remote Similarity NPC203382
0.6792 Remote Similarity NPC294938
0.6792 Remote Similarity NPC129150
0.675 Remote Similarity NPC63354
0.6667 Remote Similarity NPC223679
0.6667 Remote Similarity NPC254095
0.6604 Remote Similarity NPC51846
0.6545 Remote Similarity NPC97570
0.6545 Remote Similarity NPC82465
0.6531 Remote Similarity NPC126184
0.6481 Remote Similarity NPC249850
0.6481 Remote Similarity NPC135863
0.6481 Remote Similarity NPC293437
0.6429 Remote Similarity NPC9290
0.64 Remote Similarity NPC275316
0.64 Remote Similarity NPC15789
0.6364 Remote Similarity NPC189700
0.6364 Remote Similarity NPC21946
0.6341 Remote Similarity NPC217161
0.6327 Remote Similarity NPC90490
0.6316 Remote Similarity NPC26810
0.6304 Remote Similarity NPC57923
0.6296 Remote Similarity NPC230296
0.6275 Remote Similarity NPC43053
0.625 Remote Similarity NPC302564
0.625 Remote Similarity NPC270706
0.62 Remote Similarity NPC82446
0.614 Remote Similarity NPC98519
0.614 Remote Similarity NPC130953
0.6122 Remote Similarity NPC128280
0.6122 Remote Similarity NPC87137
0.6102 Remote Similarity NPC470808
0.6087 Remote Similarity NPC159773
0.6078 Remote Similarity NPC236338
0.6078 Remote Similarity NPC221467
0.6071 Remote Similarity NPC474084
0.6042 Remote Similarity NPC6963
0.6042 Remote Similarity NPC304079
0.6 Remote Similarity NPC19769
0.6 Remote Similarity NPC96414
0.6 Remote Similarity NPC150717
0.6 Remote Similarity NPC273600
0.5965 Remote Similarity NPC86789
0.5932 Remote Similarity NPC68110
0.5932 Remote Similarity NPC473737
0.5926 Remote Similarity NPC218486
0.5926 Remote Similarity NPC159535
0.5926 Remote Similarity NPC151761
0.5926 Remote Similarity NPC478120
0.5902 Remote Similarity NPC201356
0.5902 Remote Similarity NPC146811
0.5882 Remote Similarity NPC122212
0.5882 Remote Similarity NPC137419
0.5806 Remote Similarity NPC122627
0.58 Remote Similarity NPC308331
0.5763 Remote Similarity NPC263732
0.575 Remote Similarity NPC280312
0.575 Remote Similarity NPC8466
0.5741 Remote Similarity NPC477781
0.5741 Remote Similarity NPC477780
0.5714 Remote Similarity NPC324224
0.5714 Remote Similarity NPC245002
0.5714 Remote Similarity NPC221763
0.5714 Remote Similarity NPC472808
0.5714 Remote Similarity NPC63873
0.5667 Remote Similarity NPC475073
0.5667 Remote Similarity NPC2328
0.5645 Remote Similarity NPC475555
0.5645 Remote Similarity NPC475675
0.5645 Remote Similarity NPC276299
0.5636 Remote Similarity NPC474127
0.5636 Remote Similarity NPC135537
0.5625 Remote Similarity NPC151481
0.5625 Remote Similarity NPC475982
0.5614 Remote Similarity NPC212730
0.5614 Remote Similarity NPC265551
0.56 Remote Similarity NPC47946
0.56 Remote Similarity NPC26600

  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 NPC298413 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
0.8919 High Similarity NPD9115 Approved
0.8611 High Similarity NPD8573 Approved
0.7222 Intermediate Similarity NPD8187 Phase 3
0.641 Remote Similarity NPD9114 Clinical (unspecified phase)
0.5882 Remote Similarity NPD4220 Pre-registration
0.587 Remote Similarity NPD8839 Phase 3
0.5833 Remote Similarity NPD9411 Phase 1

  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