Structure

Physi-Chem Properties

Molecular Weight:  660.25
Volume:  627.283
LogP:  0.904
LogD:  1.783
LogS:  -3.837
# Rotatable Bonds:  6
TPSA:  205.58
# H-Bond Aceptor:  14
# H-Bond Donor:  6
# Rings:  4
# Heavy Atoms:  16

MedChem Properties

QED Drug-Likeness Score:  0.304
Synthetic Accessibility Score:  6.042
Fsp3:  0.586
Lipinski Rule-of-5:  Rejected
Pfizer Rule:  Accepted
GSK Rule:  Rejected
BMS Rule:  0
Golden Triangle Rule:  Rejected
Chelating Alert:  0
PAINS Alert:  0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:  -5.615
MDCK Permeability:  1.4048986486159265e-05
Pgp-inhibitor:  0.884
Pgp-substrate:  0.999
Human Intestinal Absorption (HIA):  0.011
20% Bioavailability (F20%):  0.971
30% Bioavailability (F30%):  0.974

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):  0.05
Plasma Protein Binding (PPB):  47.93942642211914%
Volume Distribution (VD):  0.381
Pgp-substrate:  42.29396438598633%

ADMET: Metabolism

CYP1A2-inhibitor:  0.023
CYP1A2-substrate:  0.025
CYP2C19-inhibitor:  0.222
CYP2C19-substrate:  0.045
CYP2C9-inhibitor:  0.416
CYP2C9-substrate:  0.082
CYP2D6-inhibitor:  0.002
CYP2D6-substrate:  0.111
CYP3A4-inhibitor:  0.273
CYP3A4-substrate:  0.162

ADMET: Excretion

Clearance (CL):  2.839
Half-life (T1/2):  0.193

ADMET: Toxicity

hERG Blockers:  0.006
Human Hepatotoxicity (H-HT):  0.587
Drug-inuced Liver Injury (DILI):  0.942
AMES Toxicity:  0.004
Rat Oral Acute Toxicity:  0.091
Maximum Recommended Daily Dose:  0.908
Skin Sensitization:  0.049
Carcinogencity:  0.08
Eye Corrosion:  0.003
Eye Irritation:  0.004
Respiratory Toxicity:  0.59

Download Data

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

  Natural Product: NPC103268

Natural Product ID:  NPC103268
Common Name*:   Dolastatin 3
IUPAC Name:   n.a.
Synonyms:   Dolastatin 3
Standard InCHIKey:  ATCVYMAKQRUVDS-OSAZLGQLSA-N
Standard InCHI:  InChI=1S/C29H40N8O6S2/c1-14(2)10-17-25(40)33-16(7-8-21(30)38)28-35-18(13-45-28)24(39)31-11-22-32-19(12-44-22)26(41)36-23(15(3)4)29(43)37-9-5-6-20(37)27(42)34-17/h12-17,20,23H,5-11H2,1-4H3,(H2,30,38)(H,31,39)(H,33,40)(H,34,42)(H,36,41)/t16-,17-,20-,23-/m0/s1
SMILES:  CC(C)C[C@H]1C(=N[C@@H](CCC(=N)O)c2nc(cs2)C(=NCc2nc(cs2)C(=N[C@@H](C(C)C)C(=O)N2CCC[C@H]2C(=N1)O)O)O)O
Synthetic Gene Cluster:   n.a.
ChEMBL Identifier:   CHEMBL506581
PubChem CID:   9852693
Chemical Classification**:  
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000264] Organic acids and derivatives
      • [CHEMONTID:0001813] Peptidomimetics
        • [CHEMONTID:0002010] Hybrid peptides

*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
NPO26389 Lyngbya majuscula Species Oscillatoriaceae Bacteria n.a. n.a. n.a. PMID[10514329]
NPO26389 Lyngbya majuscula Species Oscillatoriaceae Bacteria n.a. n.a. n.a. PMID[10654420]
NPO26389 Lyngbya majuscula Species Oscillatoriaceae Bacteria n.a. n.a. n.a. PMID[10691708]
NPO26389 Lyngbya majuscula Species Oscillatoriaceae Bacteria n.a. palauan n.a. PMID[10691729]
NPO26389 Lyngbya majuscula Species Oscillatoriaceae Bacteria n.a. n.a. n.a. PMID[10843570]
NPO26389 Lyngbya majuscula Species Oscillatoriaceae Bacteria n.a. n.a. n.a. PMID[10924172]
NPO26389 Lyngbya majuscula Species Oscillatoriaceae Bacteria n.a. n.a. n.a. PMID[10978206]
NPO26389 Lyngbya majuscula Species Oscillatoriaceae Bacteria n.a. n.a. n.a. PMID[11076571]
NPO26389 Lyngbya majuscula Species Oscillatoriaceae Bacteria n.a. n.a. n.a. PMID[11076573]
NPO26389 Lyngbya majuscula Species Oscillatoriaceae Bacteria n.a. n.a. n.a. PMID[11076574]
NPO26389 Lyngbya majuscula Species Oscillatoriaceae Bacteria n.a. n.a. n.a. PMID[11277744]
NPO26389 Lyngbya majuscula Species Oscillatoriaceae Bacteria n.a. n.a. n.a. PMID[11389621]
NPO26389 Lyngbya majuscula Species Oscillatoriaceae Bacteria n.a. n.a. n.a. PMID[11430000]
NPO26389 Lyngbya majuscula Species Oscillatoriaceae Bacteria n.a. n.a. n.a. PMID[11473443]
NPO26389 Lyngbya majuscula Species Oscillatoriaceae Bacteria n.a. n.a. n.a. PMID[11922791]
NPO26389 Lyngbya majuscula Species Oscillatoriaceae Bacteria n.a. n.a. n.a. PMID[12762816]
NPO26389 Lyngbya majuscula Species Oscillatoriaceae Bacteria n.a. Papua New Guinea n.a. PMID[12828459]
NPO26389 Lyngbya majuscula Species Oscillatoriaceae Bacteria n.a. n.a. n.a. PMID[14575437]
NPO26389 Lyngbya majuscula Species Oscillatoriaceae Bacteria n.a. n.a. n.a. PMID[1517734]
NPO26389 Lyngbya majuscula Species Oscillatoriaceae Bacteria n.a. Papua New Guinea n.a. PMID[16643028]
NPO26389 Lyngbya majuscula Species Oscillatoriaceae Bacteria n.a. n.a. n.a. PMID[17125217]
NPO26389 Lyngbya majuscula Species Oscillatoriaceae Bacteria n.a. n.a. n.a. PMID[17441769]
NPO26389 Lyngbya majuscula Species Oscillatoriaceae Bacteria n.a. n.a. n.a. PMID[18444683]
NPO26389 Lyngbya majuscula Species Oscillatoriaceae Bacteria n.a. Singapore n.a. PMID[19093843]
NPO26389 Lyngbya majuscula Species Oscillatoriaceae Bacteria n.a. n.a. n.a. PMID[19489598]
NPO26389 Lyngbya majuscula Species Oscillatoriaceae Bacteria n.a. eastern Caribbean n.a. PMID[19739598]
NPO26389 Lyngbya majuscula Species Oscillatoriaceae Bacteria n.a. n.a. n.a. PMID[19839606]
NPO26389 Lyngbya majuscula Species Oscillatoriaceae Bacteria n.a. n.a. n.a. PMID[20030365]
NPO26389 Lyngbya majuscula Species Oscillatoriaceae Bacteria n.a. panamanian n.a. PMID[20158242]
NPO26389 Lyngbya majuscula Species Oscillatoriaceae Bacteria n.a. Floridian n.a. PMID[20166701]
NPO26389 Lyngbya majuscula Species Oscillatoriaceae Bacteria n.a. n.a. n.a. PMID[20936843]
NPO26389 Lyngbya majuscula Species Oscillatoriaceae Bacteria n.a. n.a. n.a. PMID[21138309]
NPO26389 Lyngbya majuscula Species Oscillatoriaceae Bacteria n.a. n.a. n.a. PMID[2128518]
NPO26389 Lyngbya majuscula Species Oscillatoriaceae Bacteria n.a. n.a. n.a. PMID[21341718]
NPO26389 Lyngbya majuscula Species Oscillatoriaceae Bacteria n.a. n.a. n.a. PMID[21539315]
NPO26389 Lyngbya majuscula Species Oscillatoriaceae Bacteria n.a. n.a. n.a. PMID[21806011]
NPO26389 Lyngbya majuscula Species Oscillatoriaceae Bacteria n.a. n.a. n.a. PMID[21999614]
NPO26389 Lyngbya majuscula Species Oscillatoriaceae Bacteria n.a. n.a. n.a. PMID[22035372]
NPO26389 Lyngbya majuscula Species Oscillatoriaceae Bacteria n.a. n.a. n.a. PMID[29792428]
NPO26389 Lyngbya majuscula Species Oscillatoriaceae Bacteria n.a. n.a. n.a. PMID[3924698]
NPO26389 Lyngbya majuscula Species Oscillatoriaceae Bacteria n.a. Caribbean n.a. PMID[7623050]
NPO26389 Lyngbya majuscula Species Oscillatoriaceae Bacteria n.a. Caribbean n.a. PMID[8699186]
NPO26389 Lyngbya majuscula Species Oscillatoriaceae Bacteria n.a. n.a. n.a. PMID[9584405]
NPO26389 Lyngbya majuscula Species Oscillatoriaceae Bacteria n.a. n.a. n.a. PMID[9599278]
NPO26389 Lyngbya majuscula Species Oscillatoriaceae Bacteria n.a. n.a. n.a. PMID[9599279]
NPO26389 Lyngbya majuscula Species Oscillatoriaceae Bacteria n.a. n.a. n.a. PMID[9784156]
NPO26389 Lyngbya majuscula Species Oscillatoriaceae Bacteria 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
NPT12 Individual Protein Human immunodeficiency virus type 1 integrase Human immunodeficiency virus 1 IC50 = 5000000.0 nM PMID[481388]
NPT12 Individual Protein Human immunodeficiency virus type 1 integrase Human immunodeficiency virus 1 IC50 = 4100000.0 nM PMID[481388]
NPT168 Cell Line P388 Mus musculus ED50 = 2.7 10'-7 ug/ml PMID[481389]

☑ 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 NPC103268 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
0.8194 Intermediate Similarity NPC475390
0.777 Intermediate Similarity NPC89592
0.7761 Intermediate Similarity NPC214375
0.7622 Intermediate Similarity NPC120917
0.7609 Intermediate Similarity NPC51692
0.7552 Intermediate Similarity NPC74917
0.7234 Intermediate Similarity NPC267605
0.7176 Intermediate Similarity NPC96016
0.7143 Intermediate Similarity NPC135558
0.7125 Intermediate Similarity NPC237219
0.7099 Intermediate Similarity NPC222391
0.7025 Intermediate Similarity NPC50274
0.6975 Remote Similarity NPC110129
0.6975 Remote Similarity NPC201014
0.6867 Remote Similarity NPC256912
0.679 Remote Similarity NPC217981
0.6766 Remote Similarity NPC34319
0.6726 Remote Similarity NPC164006
0.6575 Remote Similarity NPC137705
0.6532 Remote Similarity NPC132662
0.6467 Remote Similarity NPC275393
0.6463 Remote Similarity NPC145047
0.6463 Remote Similarity NPC86490
0.6369 Remote Similarity NPC56058
0.6369 Remote Similarity NPC522
0.6264 Remote Similarity NPC122427
0.6264 Remote Similarity NPC329961
0.625 Remote Similarity NPC161242
0.625 Remote Similarity NPC469801
0.6243 Remote Similarity NPC476103
0.6196 Remote Similarity NPC165538
0.618 Remote Similarity NPC25316
0.618 Remote Similarity NPC263485
0.618 Remote Similarity NPC229160
0.6171 Remote Similarity NPC134480
0.6158 Remote Similarity NPC476080
0.6158 Remote Similarity NPC475534
0.6136 Remote Similarity NPC473704
0.6124 Remote Similarity NPC475330
0.6089 Remote Similarity NPC174652
0.6069 Remote Similarity NPC475554
0.6023 Remote Similarity NPC216720
0.5988 Remote Similarity NPC210424
0.5939 Remote Similarity NPC319751
0.5833 Remote Similarity NPC119481
0.5819 Remote Similarity NPC24990
0.5813 Remote Similarity NPC235866
0.5789 Remote Similarity NPC106235
0.5789 Remote Similarity NPC239660
0.5782 Remote Similarity NPC475196
0.5774 Remote Similarity NPC473398
0.5729 Remote Similarity NPC475350
0.5729 Remote Similarity NPC14877
0.5729 Remote Similarity NPC145178
0.569 Remote Similarity NPC315252
0.5644 Remote Similarity NPC251036
0.5631 Remote Similarity NPC478030

  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 NPC103268 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
0.6507 Remote Similarity NPD9579 Approved
0.6215 Remote Similarity NPD2957 Phase 2
0.6193 Remote Similarity NPD3876 Approved
0.6136 Remote Similarity NPD3877 Approved
0.6034 Remote Similarity NPD3966 Clinical (unspecified phase)
0.5978 Remote Similarity NPD6632 Clinical (unspecified phase)
0.5789 Remote Similarity NPD8339 Clinical (unspecified phase)
0.5754 Remote Similarity NPD3333 Approved
0.5754 Remote Similarity NPD3332 Approved
0.5714 Remote Similarity NPD6121 Clinical (unspecified phase)
0.5632 Remote Similarity NPD8030 Approved

  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