Structure

Physi-Chem Properties

Molecular Weight:  201.09
Volume:  201.741
LogP:  1.175
LogD:  0.96
LogS:  -2.957
# Rotatable Bonds:  0
TPSA:  65.28
# H-Bond Aceptor:  4
# H-Bond Donor:  4
# Rings:  3
# Heavy Atoms:  4

MedChem Properties

QED Drug-Likeness Score:  0.45
Synthetic Accessibility Score:  3.572
Fsp3:  0.091
Lipinski Rule-of-5:  Accepted
Pfizer Rule:  Accepted
GSK Rule:  Accepted
BMS Rule:  0
Golden Triangle Rule:  Accepted
Chelating Alert:  0
PAINS Alert:  0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:  -4.899
MDCK Permeability:  5.222338131716242e-06
Pgp-inhibitor:  0.0
Pgp-substrate:  0.991
Human Intestinal Absorption (HIA):  0.018
20% Bioavailability (F20%):  0.006
30% Bioavailability (F30%):  0.186

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):  0.286
Plasma Protein Binding (PPB):  64.9832763671875%
Volume Distribution (VD):  1.125
Pgp-substrate:  38.75041580200195%

ADMET: Metabolism

CYP1A2-inhibitor:  0.818
CYP1A2-substrate:  0.856
CYP2C19-inhibitor:  0.225
CYP2C19-substrate:  0.106
CYP2C9-inhibitor:  0.445
CYP2C9-substrate:  0.88
CYP2D6-inhibitor:  0.395
CYP2D6-substrate:  0.866
CYP3A4-inhibitor:  0.142
CYP3A4-substrate:  0.152

ADMET: Excretion

Clearance (CL):  9.98
Half-life (T1/2):  0.839

ADMET: Toxicity

hERG Blockers:  0.026
Human Hepatotoxicity (H-HT):  0.485
Drug-inuced Liver Injury (DILI):  0.944
AMES Toxicity:  0.878
Rat Oral Acute Toxicity:  0.967
Maximum Recommended Daily Dose:  0.444
Skin Sensitization:  0.918
Carcinogencity:  0.709
Eye Corrosion:  0.017
Eye Irritation:  0.543
Respiratory Toxicity:  0.941

Download Data

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

  Natural Product: NPC476141

Natural Product ID:  NPC476141
Common Name*:   Makaluvamine C
IUPAC Name:   n.a.
Synonyms:   Makaluvamine C; Makulavamine C
Standard InCHIKey:  XASNEYQFDOSNIH-UHFFFAOYSA-N
Standard InCHI:  InChI=1S/C11H11N3O.ClH/c1-14-3-2-6-5-13-10-9(6)8(14)4-7(12)11(10)15;/h4-5H,2-3H2,1H3,(H2,12,13,15);1H
SMILES:  CN1CCC2=C[NH+]=C3C2=C1C=C([NH-])C3=O.Cl
Synthetic Gene Cluster:   n.a.
ChEMBL Identifier:   CHEMBL540397
PubChem CID:   45259191
Chemical Classification**:  
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0001253] Quinolines and derivatives
        • [CHEMONTID:0001734] Pyrroloquinolines
          • [CHEMONTID:0002829] Pyrrolo[4,3,2-de]quinolines

*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
NPO32524 latrunculid sponges Species n.a. n.a. n.a. South African n.a. PMID[15332840]

☑ 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
NPT393 Cell Line HCT-116 Homo sapiens IC50 = 1089.0 nM PMID[514894]
NPT393 Cell Line HCT-116 Homo sapiens IC50 > 170.0 nM PMID[514896]
NPT6399 Cell Line XRS6 Cricetulus griseus IC50 = 80.0 nM PMID[514896]

☑ 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 NPC476141 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
0.7 Intermediate Similarity NPC472194
0.6702 Remote Similarity NPC477584
0.6471 Remote Similarity NPC475610
0.6344 Remote Similarity NPC28529
0.625 Remote Similarity NPC477581
0.6216 Remote Similarity NPC175585
0.616 Remote Similarity NPC476158
0.6146 Remote Similarity NPC477582
0.6105 Remote Similarity NPC77890
0.6105 Remote Similarity NPC267203
0.6105 Remote Similarity NPC132858
0.6082 Remote Similarity NPC477583
0.6061 Remote Similarity NPC76283
0.6 Remote Similarity NPC469958
0.597 Remote Similarity NPC473804
0.5963 Remote Similarity NPC58200
0.5926 Remote Similarity NPC119569
0.5922 Remote Similarity NPC236322
0.5895 Remote Similarity NPC25513
0.5851 Remote Similarity NPC281154
0.5833 Remote Similarity NPC140685
0.5816 Remote Similarity NPC312419
0.5804 Remote Similarity NPC230677
0.5789 Remote Similarity NPC472192
0.5789 Remote Similarity NPC320667
0.5789 Remote Similarity NPC214125
0.5778 Remote Similarity NPC477460
0.5778 Remote Similarity NPC76869
0.5743 Remote Similarity NPC475614
0.5727 Remote Similarity NPC34193
0.5714 Remote Similarity NPC9436
0.5686 Remote Similarity NPC202056
0.5684 Remote Similarity NPC63284
0.568 Remote Similarity NPC473249
0.5676 Remote Similarity NPC226509
0.5676 Remote Similarity NPC152718
0.5673 Remote Similarity NPC249312
0.5648 Remote Similarity NPC476449
0.5641 Remote Similarity NPC275410
0.562 Remote Similarity NPC136002
0.5612 Remote Similarity NPC157173

  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 NPC476141 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
0.6105 Remote Similarity NPD529 Approved
0.5917 Remote Similarity NPD7739 Clinical (unspecified phase)
0.5868 Remote Similarity NPD7623 Phase 3
0.5868 Remote Similarity NPD7624 Clinical (unspecified phase)
0.5833 Remote Similarity NPD1402 Approved
0.5773 Remote Similarity NPD543 Clinical (unspecified phase)
0.5729 Remote Similarity NPD836 Clinical (unspecified phase)
0.5688 Remote Similarity NPD211 Approved
0.5688 Remote Similarity NPD210 Approved
0.568 Remote Similarity NPD7747 Phase 1
0.568 Remote Similarity NPD7746 Phase 1
0.5619 Remote Similarity NPD1691 Clinical (unspecified phase)
0.5618 Remote Similarity NPD9498 Clinical (unspecified phase)
0.5618 Remote Similarity NPD1984 Approved
0.5604 Remote Similarity NPD3709 Clinical (unspecified phase)

  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