Structure

Physi-Chem Properties

Molecular Weight:  86.04
Volume:  90.048
LogP:  0.759
LogD:  0.783
LogS:  0.373
# Rotatable Bonds:  1
TPSA:  37.3
# H-Bond Aceptor:  2
# H-Bond Donor:  1
# Rings:  0
# Heavy Atoms:  2

MedChem Properties

QED Drug-Likeness Score:  0.475
Synthetic Accessibility Score:  2.663
Fsp3:  0.25
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:  -4.874
MDCK Permeability:  1.7919934180099517e-05
Pgp-inhibitor:  0.0
Pgp-substrate:  0.023
Human Intestinal Absorption (HIA):  0.015
20% Bioavailability (F20%):  0.002
30% Bioavailability (F30%):  0.136

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):  0.933
Plasma Protein Binding (PPB):  33.04345703125%
Volume Distribution (VD):  0.329
Pgp-substrate:  70.88937377929688%

ADMET: Metabolism

CYP1A2-inhibitor:  0.026
CYP1A2-substrate:  0.114
CYP2C19-inhibitor:  0.034
CYP2C19-substrate:  0.06
CYP2C9-inhibitor:  0.051
CYP2C9-substrate:  0.391
CYP2D6-inhibitor:  0.025
CYP2D6-substrate:  0.169
CYP3A4-inhibitor:  0.012
CYP3A4-substrate:  0.072

ADMET: Excretion

Clearance (CL):  4.847
Half-life (T1/2):  0.867

ADMET: Toxicity

hERG Blockers:  0.007
Human Hepatotoxicity (H-HT):  0.804
Drug-inuced Liver Injury (DILI):  0.096
AMES Toxicity:  0.029
Rat Oral Acute Toxicity:  0.421
Maximum Recommended Daily Dose:  0.045
Skin Sensitization:  0.941
Carcinogencity:  0.051
Eye Corrosion:  0.986
Eye Irritation:  0.996
Respiratory Toxicity:  0.51

Download Data

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

  Natural Product: NPC297363

Natural Product ID:  NPC297363
Common Name*:   Crotonic Acid
IUPAC Name:   (E)-but-2-enoic acid
Synonyms:   Crotonate; Crotonic Acid
Standard InCHIKey:  LDHQCZJRKDOVOX-NSCUHMNNSA-N
Standard InCHI:  InChI=1S/C4H6O2/c1-2-3-4(5)6/h2-3H,1H3,(H,5,6)/b3-2+
SMILES:  C/C=C/C(=O)O
Synthetic Gene Cluster:   n.a.
ChEMBL Identifier:   CHEMBL1213528
PubChem CID:   637090
Chemical Classification**:  
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0003909] Fatty Acyls
        • [CHEMONTID:0000262] Fatty acids and conjugates
          • [CHEMONTID:0000333] Straight chain fatty acids

*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
NPO14948 Brucea javanica Species Simaroubaceae Eukaryota n.a. seed n.a. DOI[10.1016/0031-9422(96)00258-0]
NPO14948 Brucea javanica Species Simaroubaceae Eukaryota n.a. fruit n.a. DOI[10.1016/S1383-5769(99)00023-9]
NPO14948 Brucea javanica Species Simaroubaceae Eukaryota n.a. n.a. n.a. PMID[10086989]
NPO1520 Callyspongia pseudoreticulata Species Callyspongiidae Eukaryota n.a. n.a. n.a. PMID[12828480]
NPO24252 Uvaria hamiltonii Species Annonaceae Eukaryota n.a. n.a. n.a. PMID[14552774]
NPO14948 Brucea javanica Species Simaroubaceae Eukaryota n.a. n.a. n.a. PMID[1512598]
NPO14948 Brucea javanica Species Simaroubaceae Eukaryota Seeds n.a. n.a. PMID[15165151]
NPO14948 Brucea javanica Species Simaroubaceae Eukaryota fruit Indonesia n.a. PMID[17896817]
NPO14948 Brucea javanica Species Simaroubaceae Eukaryota n.a. Vietnam n.a. PMID[19026551]
NPO14948 Brucea javanica Species Simaroubaceae Eukaryota seeds n.a. n.a. PMID[20050684]
NPO2978 Croton tiglium Species Euphorbiaceae Eukaryota n.a. seed n.a. PMID[21049973]
NPO14948 Brucea javanica Species Simaroubaceae Eukaryota Seeds n.a. n.a. PMID[22506620]
NPO2978 Croton tiglium Species Euphorbiaceae Eukaryota n.a. n.a. n.a. PMID[23701597]
NPO2978 Croton tiglium Species Euphorbiaceae Eukaryota n.a. n.a. n.a. PMID[25819096]
NPO14948 Brucea javanica Species Simaroubaceae Eukaryota n.a. n.a. n.a. PMID[6481366]
NPO14948 Brucea javanica Species Simaroubaceae Eukaryota n.a. n.a. n.a. PMID[7561896]
NPO24252 Uvaria hamiltonii Species Annonaceae Eukaryota leaf and stem n.a. n.a. PMID[9584399]
NPO14948 Brucea javanica Species Simaroubaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO2978 Croton tiglium Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO2978 Croton tiglium Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO14948 Brucea javanica Species Simaroubaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO14948 Brucea javanica Species Simaroubaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO2978 Croton tiglium Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO2978 Croton tiglium Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO14948 Brucea javanica Species Simaroubaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO14948 Brucea javanica Species Simaroubaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24585 Ocotea macropoda Species Lauraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24252 Uvaria hamiltonii Species Annonaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28694 Sanguisorba tenuifolia Species Rosaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23819 Baccharis peruviana Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1520 Callyspongia pseudoreticulata Species Callyspongiidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23277 Lobophora papenfussii Species Dictyotaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2978 Croton tiglium Species Euphorbiaceae 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 Activity = 6.0 % PMID[490614]
NPT646 Individual Protein Serine racemase Homo sapiens IC50 > 10000000.0 nM PMID[490615]
NPT647 Individual Protein D-aspartate oxidase Homo sapiens IC50 > 10000000.0 nM PMID[490615]
NPT645 Individual Protein D-amino-acid oxidase Homo sapiens IC50 = 598000.0 nM PMID[490615]
NPT645 Individual Protein D-amino-acid oxidase Homo sapiens IC50 = 357000.0 nM PMID[490615]
NPT32 Organism Mus musculus Mus musculus LD100 = 2500.0 mg kg-1 PMID[490612]
NPT32 Organism Mus musculus Mus musculus LD50 = 400.0 mg.kg-1 PMID[490612]
NPT32 Organism Mus musculus Mus musculus IC50 = 220.0 nM PMID[490613]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC > 512.0 ug.mL-1 PMID[490616]
NPT17 Organism Staphylococcus epidermidis Staphylococcus epidermidis MIC > 512.0 ug.mL-1 PMID[490616]
NPT3721 Organism Enterococcus hirae Enterococcus hirae MIC > 512.0 ug.mL-1 PMID[490616]
NPT19 Organism Escherichia coli Escherichia coli MIC > 512.0 ug.mL-1 PMID[490616]
NPT18 Organism Pseudomonas aeruginosa Pseudomonas aeruginosa MIC > 512.0 ug.mL-1 PMID[490616]

☑ 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 NPC297363 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
1.0 High Similarity NPC60675
0.9143 High Similarity NPC63598
0.9091 High Similarity NPC98098
0.9091 High Similarity NPC224651
0.8857 High Similarity NPC107877
0.8649 High Similarity NPC8270
0.8571 High Similarity NPC308418
0.8421 Intermediate Similarity NPC221250
0.8378 Intermediate Similarity NPC298413
0.8205 Intermediate Similarity NPC102879
0.8125 Intermediate Similarity NPC20903
0.7879 Intermediate Similarity NPC323552
0.775 Intermediate Similarity NPC41409
0.75 Intermediate Similarity NPC217161
0.725 Intermediate Similarity NPC297608
0.7 Intermediate Similarity NPC147824
0.6977 Remote Similarity NPC304079
0.6977 Remote Similarity NPC6963
0.6957 Remote Similarity NPC221467
0.6889 Remote Similarity NPC128520
0.6842 Remote Similarity NPC122676
0.6829 Remote Similarity NPC281043
0.6829 Remote Similarity NPC250954
0.6809 Remote Similarity NPC43053
0.6667 Remote Similarity NPC87137
0.6667 Remote Similarity NPC308331
0.64 Remote Similarity NPC474127
0.6389 Remote Similarity NPC8466
0.6389 Remote Similarity NPC280312
0.6383 Remote Similarity NPC137419
0.6383 Remote Similarity NPC126184
0.6383 Remote Similarity NPC122212
0.625 Remote Similarity NPC65353
0.617 Remote Similarity NPC90490
0.6154 Remote Similarity NPC324224
0.6154 Remote Similarity NPC472808
0.6154 Remote Similarity NPC63354
0.6047 Remote Similarity NPC203382
0.6042 Remote Similarity NPC82446
0.6038 Remote Similarity NPC129150
0.6038 Remote Similarity NPC294938
0.5926 Remote Similarity NPC189700
0.5926 Remote Similarity NPC254095
0.5926 Remote Similarity NPC474084
0.5926 Remote Similarity NPC223679
0.5918 Remote Similarity NPC275316
0.5918 Remote Similarity NPC15789
0.5897 Remote Similarity NPC144407
0.5854 Remote Similarity NPC9290
0.5849 Remote Similarity NPC51846
0.5818 Remote Similarity NPC82465
0.5818 Remote Similarity NPC302564
0.5818 Remote Similarity NPC97570
0.5789 Remote Similarity NPC242117
0.5778 Remote Similarity NPC57923
0.5778 Remote Similarity NPC169098
0.5769 Remote Similarity NPC218486
0.575 Remote Similarity NPC146507
0.575 Remote Similarity NPC250734
0.575 Remote Similarity NPC310810
0.5745 Remote Similarity NPC270706
0.5741 Remote Similarity NPC293437
0.5741 Remote Similarity NPC135863
0.5741 Remote Similarity NPC249850
0.5741 Remote Similarity NPC283502
0.5714 Remote Similarity NPC130953
0.5714 Remote Similarity NPC313553
0.5652 Remote Similarity NPC270796
0.5641 Remote Similarity NPC273054
0.5636 Remote Similarity NPC34416
0.5636 Remote Similarity NPC471619
0.5636 Remote Similarity NPC21946
0.5625 Remote Similarity NPC128280
0.5614 Remote Similarity NPC26810
0.561 Remote Similarity NPC72258
0.561 Remote Similarity NPC58957
0.56 Remote Similarity NPC236338

  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 NPC297363 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
0.9091 High Similarity NPD8573 Approved
0.8125 Intermediate Similarity NPD8187 Phase 3
0.7368 Intermediate Similarity NPD9115 Approved
0.6739 Remote Similarity NPD4220 Pre-registration
0.6667 Remote Similarity NPD9114 Clinical (unspecified phase)
0.6 Remote Similarity NPD9411 Phase 1
0.5652 Remote Similarity NPD5326 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