Structure

Physi-Chem Properties

Molecular Weight:  174.02
Volume:  154.528
LogP:  -0.296
LogD:  2.563
LogS:  -0.291
# Rotatable Bonds:  4
TPSA:  111.9
# H-Bond Aceptor:  6
# H-Bond Donor:  3
# Rings:  0
# Heavy Atoms:  6

MedChem Properties

QED Drug-Likeness Score:  0.498
Synthetic Accessibility Score:  2.613
Fsp3:  0.167
Lipinski Rule-of-5:  Accepted
Pfizer Rule:  Accepted
GSK Rule:  Accepted
BMS Rule:  1
Golden Triangle Rule:  Rejected
Chelating Alert:  0
PAINS Alert:  0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:  -6.025
MDCK Permeability:  0.00014133646618574858
Pgp-inhibitor:  0.0
Pgp-substrate:  0.002
Human Intestinal Absorption (HIA):  0.913
20% Bioavailability (F20%):  0.287
30% Bioavailability (F30%):  0.908

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):  0.037
Plasma Protein Binding (PPB):  29.432273864746094%
Volume Distribution (VD):  0.397
Pgp-substrate:  41.40392303466797%

ADMET: Metabolism

CYP1A2-inhibitor:  0.005
CYP1A2-substrate:  0.021
CYP2C19-inhibitor:  0.035
CYP2C19-substrate:  0.03
CYP2C9-inhibitor:  0.21
CYP2C9-substrate:  0.188
CYP2D6-inhibitor:  0.028
CYP2D6-substrate:  0.076
CYP3A4-inhibitor:  0.019
CYP3A4-substrate:  0.003

ADMET: Excretion

Clearance (CL):  1.675
Half-life (T1/2):  0.941

ADMET: Toxicity

hERG Blockers:  0.003
Human Hepatotoxicity (H-HT):  0.342
Drug-inuced Liver Injury (DILI):  0.782
AMES Toxicity:  0.034
Rat Oral Acute Toxicity:  0.035
Maximum Recommended Daily Dose:  0.004
Skin Sensitization:  0.93
Carcinogencity:  0.019
Eye Corrosion:  0.996
Eye Irritation:  0.989
Respiratory Toxicity:  0.168

Download Data

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

  Natural Product: NPC137419

Natural Product ID:  NPC137419
Common Name*:   Aconitic Acid
IUPAC Name:   (E)-prop-1-ene-1,2,3-tricarboxylic acid
Synonyms:  
Standard InCHIKey:  GTZCVFVGUGFEME-HNQUOIGGSA-N
Standard InCHI:  InChI=1S/C6H6O6/c7-4(8)1-3(6(11)12)2-5(9)10/h1H,2H2,(H,7,8)(H,9,10)(H,11,12)/b3-1+
SMILES:  C(=C(CC(=O)O)/C(=O)O)C(=O)O
Synthetic Gene Cluster:   BGC0001809;
ChEMBL Identifier:   CHEMBL153658
PubChem CID:   444212
Chemical Classification**:  
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000264] Organic acids and derivatives
      • [CHEMONTID:0000265] Carboxylic acids and derivatives
        • [CHEMONTID:0001986] Tricarboxylic acids and derivatives

*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

☑ 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
NPT48 Individual Protein Lysine-specific demethylase 4D-like Homo sapiens Potency = 39810.7 nM PMID[518029]
NPT210 Individual Protein Thyroid stimulating hormone receptor Homo sapiens Potency = 5011.9 nM PMID[518030]
NPT55 Individual Protein Putative fructose-1,6-bisphosphate aldolase Giardia intestinalis Potency = 12559.4 nM PMID[518029]
NPT2 Others Unspecified Potency n.a. 266 nM PubChem BioAssay data set
NPT2 Others Unspecified Potency n.a. 10590.1 nM PubChem BioAssay data set
NPT945 Individual Protein ATP-citrate synthase Rattus norvegicus Ki > 1000000.0 nM PMID[518028]
NPT73 Individual Protein Solute carrier organic anion transporter family member 1B1 Homo sapiens Inhibition = 102.5 % PMID[518031]
NPT72 Individual Protein Solute carrier organic anion transporter family member 1B3 Homo sapiens Inhibition = 88.62 % PMID[518031]
NPT2 Others Unspecified Ac50 n.a. 0.631 uM PMID[518032]
NPT2 Others Unspecified AC50 n.a. 631.0 nM PMID[518032]
NPT2 Others Unspecified Ac50 n.a. 10.0 uM PMID[518032]
NPT2 Others Unspecified AC50 n.a. 10000.0 nM PMID[518032]
NPT2 Others Unspecified Ki = 6130.0 nM PMID[518033]
NPT2 Others Unspecified Activity = 33.8 % PMID[518033]
NPT2 Others Unspecified IC50 = 5020000.0 nM PMID[518034]

☑ 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 NPC137419 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 NPC122212
0.8723 High Similarity NPC87137
0.8667 High Similarity NPC169098
0.8333 Intermediate Similarity NPC471619
0.7358 Intermediate Similarity NPC43053
0.717 Intermediate Similarity NPC221467
0.7083 Intermediate Similarity NPC8270
0.7018 Intermediate Similarity NPC51846
0.6964 Remote Similarity NPC474127
0.6939 Remote Similarity NPC221250
0.6897 Remote Similarity NPC283502
0.6863 Remote Similarity NPC304079
0.6863 Remote Similarity NPC6963
0.6727 Remote Similarity NPC15129
0.6667 Remote Similarity NPC202011
0.6613 Remote Similarity NPC68110
0.661 Remote Similarity NPC135863
0.661 Remote Similarity NPC249850
0.661 Remote Similarity NPC293437
0.6604 Remote Similarity NPC308331
0.6596 Remote Similarity NPC308418
0.6522 Remote Similarity NPC122471
0.6522 Remote Similarity NPC217161
0.6522 Remote Similarity NPC224651
0.6522 Remote Similarity NPC98098
0.65 Remote Similarity NPC189700
0.65 Remote Similarity NPC34416
0.65 Remote Similarity NPC254095
0.6471 Remote Similarity NPC190649
0.6458 Remote Similarity NPC107877
0.6393 Remote Similarity NPC86789
0.6383 Remote Similarity NPC297363
0.6383 Remote Similarity NPC60675
0.6379 Remote Similarity NPC154626
0.6377 Remote Similarity NPC114727
0.6377 Remote Similarity NPC476590
0.629 Remote Similarity NPC472328
0.629 Remote Similarity NPC98519
0.6286 Remote Similarity NPC478191
0.6286 Remote Similarity NPC478196
0.6286 Remote Similarity NPC478192
0.6286 Remote Similarity NPC478195
0.6286 Remote Similarity NPC478193
0.6286 Remote Similarity NPC478194
0.625 Remote Similarity NPC15789
0.6232 Remote Similarity NPC284006
0.623 Remote Similarity NPC21946
0.623 Remote Similarity NPC223679
0.6197 Remote Similarity NPC470705
0.619 Remote Similarity NPC263732
0.6154 Remote Similarity NPC273600
0.6154 Remote Similarity NPC470123
0.6129 Remote Similarity NPC82465
0.6111 Remote Similarity NPC47844
0.6111 Remote Similarity NPC141195
0.6102 Remote Similarity NPC218486
0.6102 Remote Similarity NPC135537
0.6094 Remote Similarity NPC473737
0.6094 Remote Similarity NPC2328
0.6094 Remote Similarity NPC475073
0.6071 Remote Similarity NPC313553
0.6066 Remote Similarity NPC268185
0.6066 Remote Similarity NPC71755
0.6066 Remote Similarity NPC294938
0.6066 Remote Similarity NPC129150
0.6061 Remote Similarity NPC322035
0.6061 Remote Similarity NPC100719
0.6061 Remote Similarity NPC308294
0.6061 Remote Similarity NPC166791
0.6061 Remote Similarity NPC142423
0.6056 Remote Similarity NPC161038
0.6038 Remote Similarity NPC40805
0.6038 Remote Similarity NPC270796
0.6034 Remote Similarity NPC137396
0.6032 Remote Similarity NPC305973
0.6032 Remote Similarity NPC130953
0.6032 Remote Similarity NPC309408
0.6029 Remote Similarity NPC475982
0.6027 Remote Similarity NPC28049
0.6 Remote Similarity NPC49028
0.6 Remote Similarity NPC12815
0.6 Remote Similarity NPC173157
0.6 Remote Similarity NPC215745
0.6 Remote Similarity NPC63598
0.6 Remote Similarity NPC238948
0.6 Remote Similarity NPC470325
0.6 Remote Similarity NPC53642
0.5972 Remote Similarity NPC256640
0.5972 Remote Similarity NPC205615
0.5972 Remote Similarity NPC16279
0.5972 Remote Similarity NPC68819
0.597 Remote Similarity NPC7392
0.597 Remote Similarity NPC122627
0.597 Remote Similarity NPC98329
0.5965 Remote Similarity NPC236338
0.5938 Remote Similarity NPC26810
0.5909 Remote Similarity NPC19769
0.5909 Remote Similarity NPC471556
0.5909 Remote Similarity NPC471566
0.5909 Remote Similarity NPC471565
0.5909 Remote Similarity NPC282760
0.5902 Remote Similarity NPC324224
0.5902 Remote Similarity NPC472808
0.589 Remote Similarity NPC275530
0.5882 Remote Similarity NPC298413
0.5873 Remote Similarity NPC322002
0.5873 Remote Similarity NPC322186
0.5873 Remote Similarity NPC97570
0.5862 Remote Similarity NPC178586
0.5833 Remote Similarity NPC322461
0.5833 Remote Similarity NPC189677
0.5833 Remote Similarity NPC478120
0.5821 Remote Similarity NPC475555
0.5821 Remote Similarity NPC248125
0.5821 Remote Similarity NPC475675
0.5821 Remote Similarity NPC472072
0.5818 Remote Similarity NPC117572
0.5818 Remote Similarity NPC270706
0.5811 Remote Similarity NPC93763
0.5811 Remote Similarity NPC108816
0.5797 Remote Similarity NPC236208
0.5797 Remote Similarity NPC476591
0.5797 Remote Similarity NPC88877
0.5789 Remote Similarity NPC135698
0.5789 Remote Similarity NPC474980
0.5789 Remote Similarity NPC267110
0.5781 Remote Similarity NPC79756
0.5778 Remote Similarity NPC236709
0.5769 Remote Similarity NPC44546
0.5763 Remote Similarity NPC191643
0.5758 Remote Similarity NPC133758
0.5758 Remote Similarity NPC4668
0.5758 Remote Similarity NPC471611
0.5753 Remote Similarity NPC4492
0.5753 Remote Similarity NPC209113
0.5753 Remote Similarity NPC301207
0.5753 Remote Similarity NPC51391
0.5753 Remote Similarity NPC127118
0.5714 Remote Similarity NPC133700
0.5714 Remote Similarity NPC475046
0.5714 Remote Similarity NPC11383
0.5714 Remote Similarity NPC269641
0.5714 Remote Similarity NPC67183
0.5714 Remote Similarity NPC42304
0.5714 Remote Similarity NPC474084
0.5714 Remote Similarity NPC474959
0.5714 Remote Similarity NPC310450
0.5714 Remote Similarity NPC128280
0.5692 Remote Similarity NPC151648
0.5692 Remote Similarity NPC269737
0.5692 Remote Similarity NPC273614
0.5692 Remote Similarity NPC64985
0.569 Remote Similarity NPC225974
0.5676 Remote Similarity NPC125365
0.5676 Remote Similarity NPC474818
0.5676 Remote Similarity NPC51809
0.5676 Remote Similarity NPC49302
0.5676 Remote Similarity NPC176329
0.5672 Remote Similarity NPC96414
0.5667 Remote Similarity NPC116366
0.5652 Remote Similarity NPC323552
0.5652 Remote Similarity NPC63873
0.5652 Remote Similarity NPC287705
0.5645 Remote Similarity NPC325977
0.5645 Remote Similarity NPC150717
0.5645 Remote Similarity NPC230296
0.5641 Remote Similarity NPC40746
0.5641 Remote Similarity NPC229799
0.5641 Remote Similarity NPC286770
0.5641 Remote Similarity NPC169575
0.5641 Remote Similarity NPC284472
0.5641 Remote Similarity NPC116543
0.5634 Remote Similarity NPC319163
0.5634 Remote Similarity NPC316185
0.5634 Remote Similarity NPC67076
0.5625 Remote Similarity NPC302564
0.5625 Remote Similarity NPC329249
0.5625 Remote Similarity NPC318306
0.5616 Remote Similarity NPC166018
0.5616 Remote Similarity NPC472327
0.5616 Remote Similarity NPC169056
0.5616 Remote Similarity NPC225665
0.5614 Remote Similarity NPC91495
0.5614 Remote Similarity NPC207292
0.5606 Remote Similarity NPC322457
0.5606 Remote Similarity NPC474658
0.5606 Remote Similarity NPC190049
0.56 Remote Similarity NPC221095
0.56 Remote Similarity NPC473471
0.56 Remote Similarity NPC182292
0.56 Remote Similarity NPC279214

  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 NPC137419 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
0.7708 Intermediate Similarity NPD9411 Phase 1
0.6522 Remote Similarity NPD8573 Approved
0.6364 Remote Similarity NPD4220 Pre-registration
0.6038 Remote Similarity NPD5326 Phase 3
0.597 Remote Similarity NPD9137 Approved
0.587 Remote Similarity NPD9114 Clinical (unspecified phase)
0.5818 Remote Similarity NPD39 Approved
0.5818 Remote Similarity NPD4222 Approved
0.5778 Remote Similarity NPD8593 Approved
0.5778 Remote Similarity NPD8594 Approved
0.5676 Remote Similarity NPD4756 Discovery

  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