Structure

Physi-Chem Properties

Molecular Weight:  505.29
Volume:  533.369
LogP:  3.834
LogD:  3.527
LogS:  -4.529
# Rotatable Bonds:  2
TPSA:  96.72
# H-Bond Aceptor:  6
# H-Bond Donor:  2
# Rings:  2
# Heavy Atoms:  7

MedChem Properties

QED Drug-Likeness Score:  0.398
Synthetic Accessibility Score:  4.801
Fsp3:  0.679
Lipinski Rule-of-5:  Accepted
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:  -4.775
MDCK Permeability:  2.895371289923787e-05
Pgp-inhibitor:  0.868
Pgp-substrate:  0.997
Human Intestinal Absorption (HIA):  0.02
20% Bioavailability (F20%):  0.989
30% Bioavailability (F30%):  0.989

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):  0.526
Plasma Protein Binding (PPB):  94.84760284423828%
Volume Distribution (VD):  0.574
Pgp-substrate:  3.8863630294799805%

ADMET: Metabolism

CYP1A2-inhibitor:  0.112
CYP1A2-substrate:  0.377
CYP2C19-inhibitor:  0.426
CYP2C19-substrate:  0.254
CYP2C9-inhibitor:  0.45
CYP2C9-substrate:  0.726
CYP2D6-inhibitor:  0.017
CYP2D6-substrate:  0.542
CYP3A4-inhibitor:  0.863
CYP3A4-substrate:  0.52

ADMET: Excretion

Clearance (CL):  10.364
Half-life (T1/2):  0.394

ADMET: Toxicity

hERG Blockers:  0.094
Human Hepatotoxicity (H-HT):  0.925
Drug-inuced Liver Injury (DILI):  0.74
AMES Toxicity:  0.104
Rat Oral Acute Toxicity:  0.932
Maximum Recommended Daily Dose:  0.92
Skin Sensitization:  0.348
Carcinogencity:  0.871
Eye Corrosion:  0.039
Eye Irritation:  0.012
Respiratory Toxicity:  0.973

Download Data

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

  Natural Product: NPC45576

Natural Product ID:  NPC45576
Common Name*:   Epothilone I1
IUPAC Name:   (4S,7R,8S,9S,15Z,18S)-4,8-dihydroxy-5,5,7,9-tetramethyl-18-[(E)-1-(2-methyl-1,3-thiazol-4-yl)prop-1-en-2-yl]-1-oxacyclooctadec-15-ene-2,6-dione
Synonyms:   Epothilone I1
Standard InCHIKey:  MLQWYAQKRLGGTG-ZBUSTYTQSA-N
Standard InCHI:  InChI=1S/C28H43NO5S/c1-18-13-11-9-7-8-10-12-14-23(19(2)15-22-17-35-21(4)29-22)34-25(31)16-24(30)28(5,6)27(33)20(3)26(18)32/h10,12,15,17-18,20,23-24,26,30,32H,7-9,11,13-14,16H2,1-6H3/b12-10-,19-15+/t18-,20+,23-,24-,26-/m0/s1
SMILES:  C[C@H]1CCCCC/C=CC[C@@H](/C(=C/c2csc(C)n2)/C)OC(=O)C[C@@H](C(C)(C)C(=O)[C@H](C)[C@H]1O)O
Synthetic Gene Cluster:   n.a.
ChEMBL Identifier:   CHEMBL460233
PubChem CID:   10505737
Chemical Classification**:  
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000147] Macrolides and analogues

*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
NPO32627 sorangium cellulosum, strains so ce90/b2 Species Polyangiaceae Bacteria n.a. n.a. n.a. PMID[11473410]

☑ 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
NPT1460 Cell Line L929 Mus musculus IC50 = 0.8 ug.mL-1 PMID[537055]

☑ 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 NPC45576 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 NPC109498
1.0 High Similarity NPC474090
1.0 High Similarity NPC32583
1.0 High Similarity NPC61667
1.0 High Similarity NPC163147
1.0 High Similarity NPC252616
0.993 High Similarity NPC224609
0.993 High Similarity NPC268063
0.9929 High Similarity NPC475737
0.9929 High Similarity NPC474094
0.9929 High Similarity NPC185665
0.9929 High Similarity NPC474067
0.9859 High Similarity NPC154873
0.9858 High Similarity NPC474102
0.9858 High Similarity NPC21449
0.9858 High Similarity NPC474079
0.9858 High Similarity NPC475683
0.9858 High Similarity NPC474080
0.9858 High Similarity NPC157194
0.9787 High Similarity NPC82436
0.9787 High Similarity NPC474064
0.9787 High Similarity NPC474068
0.9787 High Similarity NPC474103
0.9724 High Similarity NPC127775
0.9586 High Similarity NPC202591
0.9586 High Similarity NPC212214
0.9574 High Similarity NPC474069
0.9521 High Similarity NPC21126
0.9456 High Similarity NPC474538
0.9456 High Similarity NPC52587
0.9448 High Similarity NPC474515
0.9448 High Similarity NPC206724
0.9392 High Similarity NPC231110
0.9329 High Similarity NPC312887
0.8803 High Similarity NPC474070
0.831 Intermediate Similarity NPC475604
0.8099 Intermediate Similarity NPC475568
0.7439 Intermediate Similarity NPC315252
0.7405 Intermediate Similarity NPC190329
0.7278 Intermediate Similarity NPC469801
0.725 Intermediate Similarity NPC319751
0.7246 Intermediate Similarity NPC211555
0.7186 Intermediate Similarity NPC186452
0.7117 Intermediate Similarity NPC119481
0.7055 Intermediate Similarity NPC473398
0.7018 Intermediate Similarity NPC12660
0.6977 Remote Similarity NPC54983
0.6839 Remote Similarity NPC101980
0.6839 Remote Similarity NPC470146
0.6839 Remote Similarity NPC97078
0.6457 Remote Similarity NPC56058
0.6457 Remote Similarity NPC522
0.6455 Remote Similarity NPC165538
0.6436 Remote Similarity NPC122427
0.6425 Remote Similarity NPC164006
0.6364 Remote Similarity NPC210424
0.6351 Remote Similarity NPC469858
0.6349 Remote Similarity NPC329961
0.6348 Remote Similarity NPC475554
0.6307 Remote Similarity NPC216720
0.6301 Remote Similarity NPC14101
0.625 Remote Similarity NPC132662
0.6219 Remote Similarity NPC145178
0.6219 Remote Similarity NPC475350
0.6219 Remote Similarity NPC14877
0.6188 Remote Similarity NPC24990
0.6141 Remote Similarity NPC473704
0.6127 Remote Similarity NPC251036
0.6087 Remote Similarity NPC134480
0.6077 Remote Similarity NPC473886
0.6075 Remote Similarity NPC161242
0.5989 Remote Similarity NPC475534
0.5989 Remote Similarity NPC476080
0.5988 Remote Similarity NPC475390
0.5978 Remote Similarity NPC476103
0.5969 Remote Similarity NPC239660
0.5969 Remote Similarity NPC106235
0.5945 Remote Similarity NPC475196
0.5926 Remote Similarity NPC229160
0.5926 Remote Similarity NPC25316
0.5926 Remote Similarity NPC263485
0.5873 Remote Similarity NPC475330
0.5864 Remote Similarity NPC161143
0.5842 Remote Similarity NPC174652
0.578 Remote Similarity NPC478252
0.578 Remote Similarity NPC478251
0.5668 Remote Similarity NPC30527
0.5632 Remote Similarity NPC160222
0.5632 Remote Similarity NPC193753
0.561 Remote Similarity NPC267605
0.5602 Remote Similarity NPC475455

  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 NPC45576 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
0.9929 High Similarity NPD6907 Phase 2
0.9521 High Similarity NPD6910 Phase 3
0.9257 High Similarity NPD6911 Discontinued
0.9026 High Similarity NPD6916 Clinical (unspecified phase)
0.8442 Intermediate Similarity NPD6915 Approved
0.7202 Intermediate Similarity NPD7496 Phase 2
0.6453 Remote Similarity NPD5189 Clinical (unspecified phase)
0.6393 Remote Similarity NPD2957 Phase 2
0.6379 Remote Similarity NPD5634 Approved
0.6159 Remote Similarity NPD1083 Clinical (unspecified phase)
0.612 Remote Similarity NPD6870 Phase 1
0.5969 Remote Similarity NPD8339 Clinical (unspecified phase)
0.5928 Remote Similarity NPD6348 Clinical (unspecified phase)
0.5795 Remote Similarity NPD6349 Phase 1
0.5737 Remote Similarity NPD6642 Approved
0.5737 Remote Similarity NPD6641 Approved
0.5699 Remote Similarity NPD7977 Clinical (unspecified phase)
0.5657 Remote Similarity NPD4949 Discontinued
0.5652 Remote Similarity NPD8071 Approved
0.5608 Remote Similarity NPD6739 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