Structure

Physi-Chem Properties

Molecular Weight:  491.27
Volume:  516.073
LogP:  3.496
LogD:  3.501
LogS:  -4.678
# 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:  0.432
Synthetic Accessibility Score:  4.847
Fsp3:  0.667
Lipinski Rule-of-5:  Accepted
Pfizer Rule:  Accepted
GSK Rule:  Rejected
BMS Rule:  0
Golden Triangle Rule:  Accepted
Chelating Alert:  0
PAINS Alert:  0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:  -4.652
MDCK Permeability:  2.7552665414987132e-05
Pgp-inhibitor:  0.987
Pgp-substrate:  0.997
Human Intestinal Absorption (HIA):  0.012
20% Bioavailability (F20%):  0.85
30% Bioavailability (F30%):  0.969

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):  0.646
Plasma Protein Binding (PPB):  93.99141693115234%
Volume Distribution (VD):  0.467
Pgp-substrate:  5.586124420166016%

ADMET: Metabolism

CYP1A2-inhibitor:  0.078
CYP1A2-substrate:  0.198
CYP2C19-inhibitor:  0.308
CYP2C19-substrate:  0.366
CYP2C9-inhibitor:  0.212
CYP2C9-substrate:  0.458
CYP2D6-inhibitor:  0.015
CYP2D6-substrate:  0.573
CYP3A4-inhibitor:  0.69
CYP3A4-substrate:  0.556

ADMET: Excretion

Clearance (CL):  11.519
Half-life (T1/2):  0.173

ADMET: Toxicity

hERG Blockers:  0.052
Human Hepatotoxicity (H-HT):  0.941
Drug-inuced Liver Injury (DILI):  0.826
AMES Toxicity:  0.039
Rat Oral Acute Toxicity:  0.903
Maximum Recommended Daily Dose:  0.916
Skin Sensitization:  0.287
Carcinogencity:  0.898
Eye Corrosion:  0.042
Eye Irritation:  0.012
Respiratory Toxicity:  0.97

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General Info & Identifiers & Properties  
Structure MOL file  
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Biological Activities  
Similar NPs/Drugs  

  Natural Product: NPC185665

Natural Product ID:  NPC185665
Common Name*:   Epothilone D
IUPAC Name:   (4S,7R,8S,9S,13Z,16S)-4,8-dihydroxy-5,5,7,9,13-pentamethyl-16-[(E)-1-(2-methyl-1,3-thiazol-4-yl)prop-1-en-2-yl]-1-oxacyclohexadec-13-ene-2,6-dione
Synonyms:   Epothilone D
Standard InCHIKey:  XOZIUKBZLSUILX-GIQCAXHBSA-N
Standard InCHI:  InChI=1S/C27H41NO5S/c1-16-9-8-10-17(2)25(31)19(4)26(32)27(6,7)23(29)14-24(30)33-22(12-11-16)18(3)13-21-15-34-20(5)28-21/h11,13,15,17,19,22-23,25,29,31H,8-10,12,14H2,1-7H3/b16-11-,18-13+/t17-,19+,22-,23-,25-/m0/s1
SMILES:  O=C1O[C@@H](C/C=C(/C)CCC[C@@H]([C@@H]([C@H](C(=O)C([C@H](C1)O)(C)C)C)O)C)/C(=C/c1csc(n1)C)/C
Synthetic Gene Cluster:   n.a.
ChEMBL Identifier:   CHEMBL96172
PubChem CID:   447865
Chemical Classification**:  
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000147] Macrolides and analogues
        • [CHEMONTID:0000161] Epothilones 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]
NPO17888 Myxococcus xanthus Species Myxococcaceae Bacteria n.a. n.a. n.a. PMID[12141877]
NPO17888 Myxococcus xanthus Species Myxococcaceae Bacteria n.a. n.a. n.a. PMID[14575429]
NPO17888 Myxococcus xanthus Species Myxococcaceae Bacteria n.a. n.a. n.a. PMID[31465225]
NPO17888 Myxococcus xanthus Species Myxococcaceae 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
NPT1178 Cell Line KB 3-1 Homo sapiens IC50 = 2.7 nM PMID[504078]
NPT91 Cell Line KB Homo sapiens IC50 = 1.44 nM PMID[504078]
NPT1460 Cell Line L929 Mus musculus IC50 = 0.02 ug.mL-1 PMID[504079]
NPT83 Cell Line MCF7 Homo sapiens IC50 = 8.0 nM PMID[504080]
NPT378 Cell Line NCI/ADR-RES Homo sapiens IC50 = 30.0 nM PMID[504080]
NPT395 Cell Line SF-268 Homo sapiens IC50 = 14.0 nM PMID[504080]
NPT397 Cell Line NCI-H460 Homo sapiens IC50 = 8.0 nM PMID[504080]
NPT116 Cell Line HL-60 Homo sapiens IC50 = 8.0 nM PMID[504080]
NPT116 Cell Line HL-60 Homo sapiens IC50 = 10.0 nM PMID[504080]
NPT404 Cell Line CCRF-CEM Homo sapiens IC50 = 22.0 nM PMID[504080]
NPT404 Cell Line CCRF-CEM Homo sapiens IC50 = 15.0 nM PMID[504080]
NPT83 Cell Line MCF7 Homo sapiens IC50 = 16.0 nM PMID[504081]
NPT395 Cell Line SF-268 Homo sapiens IC50 = 18.0 nM PMID[504081]
NPT397 Cell Line NCI-H460 Homo sapiens IC50 = 30.0 nM PMID[504081]
NPT367 Cell Line MDA-N Homo sapiens GI50 n.a. 0.1 nM PMID[504082]
NPT368 Cell Line SN12C Homo sapiens GI50 n.a. 0.1 nM PMID[504082]
NPT369 Cell Line ACHN Homo sapiens GI50 n.a. 0.1 nM PMID[504082]
NPT370 Cell Line NCI-H23 Homo sapiens GI50 n.a. 0.1 nM PMID[504082]
NPT371 Cell Line UO-31 Homo sapiens GI50 n.a. 0.1 nM PMID[504082]
NPT372 Cell Line HOP-92 Homo sapiens GI50 n.a. 140.93 nM PMID[504082]
NPT90 Cell Line DU-145 Homo sapiens GI50 n.a. 0.1 nM PMID[504082]
NPT373 Cell Line SK-MEL-5 Homo sapiens GI50 n.a. 0.1 nM PMID[504082]
NPT374 Cell Line SF-539 Homo sapiens GI50 n.a. 0.1 nM PMID[504082]
NPT111 Cell Line K562 Homo sapiens GI50 n.a. 0.1 nM PMID[504082]
NPT377 Cell Line OVCAR-3 Homo sapiens GI50 n.a. 0.1 nM PMID[504082]
NPT112 Cell Line MOLT-4 Homo sapiens GI50 n.a. 0.1 nM PMID[504082]
NPT379 Cell Line HOP-62 Homo sapiens GI50 n.a. 0.1 nM PMID[504082]
NPT378 Cell Line NCI/ADR-RES Homo sapiens GI50 n.a. 0.1 nM PMID[504082]
NPT381 Cell Line OVCAR-8 Homo sapiens GI50 n.a. 0.1 nM PMID[504082]
NPT380 Cell Line U-251 Homo sapiens GI50 n.a. 0.1 nM PMID[504082]
NPT382 Cell Line OVCAR-5 Homo sapiens GI50 n.a. 0.1 nM PMID[504082]
NPT383 Cell Line SNB-19 Homo sapiens GI50 n.a. 0.1 nM PMID[504082]
NPT82 Cell Line MDA-MB-231 Homo sapiens GI50 n.a. 0.1 nM PMID[504082]
NPT385 Cell Line SR Homo sapiens GI50 n.a. 0.1 nM PMID[504082]
NPT384 Cell Line TK-10 Homo sapiens GI50 n.a. 0.1923 nM PMID[504082]
NPT323 Cell Line SW-620 Homo sapiens GI50 n.a. 0.1 nM PMID[504082]
NPT386 Cell Line KM12 Homo sapiens GI50 n.a. 0.1 nM PMID[504082]
NPT455 Cell Line NCI-H522 Homo sapiens GI50 n.a. 0.1 nM PMID[504082]
NPT387 Cell Line M14 Homo sapiens GI50 n.a. 0.1 nM PMID[504082]
NPT388 Cell Line NCI-H322M Homo sapiens GI50 n.a. 0.1 nM PMID[504082]
NPT389 Cell Line RPMI-8226 Homo sapiens GI50 n.a. 0.1 nM PMID[504082]
NPT456 Cell Line OVCAR-4 Homo sapiens GI50 n.a. 136.77 nM PMID[504082]
NPT390 Cell Line LOX IMVI Homo sapiens GI50 n.a. 0.1 nM PMID[504082]
NPT457 Cell Line BT-549 Homo sapiens GI50 n.a. 0.1 nM PMID[504082]
NPT147 Cell Line SK-MEL-2 Homo sapiens GI50 n.a. 0.1 nM PMID[504082]
NPT391 Cell Line HCC 2998 Homo sapiens GI50 n.a. 0.1 nM PMID[504082]
NPT81 Cell Line A549 Homo sapiens GI50 n.a. 0.1 nM PMID[504082]
NPT392 Cell Line SNB-75 Homo sapiens GI50 n.a. 0.1 nM PMID[504082]
NPT148 Cell Line HCT-15 Homo sapiens GI50 n.a. 0.1 nM PMID[504082]
NPT393 Cell Line HCT-116 Homo sapiens GI50 n.a. 0.1 nM PMID[504082]
NPT395 Cell Line SF-268 Homo sapiens GI50 n.a. 0.1 nM PMID[504082]
NPT394 Cell Line EKVX Homo sapiens GI50 n.a. 0.1 nM PMID[504082]
NPT83 Cell Line MCF7 Homo sapiens GI50 n.a. 0.1 nM PMID[504082]
NPT306 Cell Line PC-3 Homo sapiens GI50 n.a. 0.1 nM PMID[504082]
NPT146 Cell Line SK-OV-3 Homo sapiens GI50 n.a. 0.1 nM PMID[504082]
NPT396 Cell Line T47D Homo sapiens GI50 n.a. 0.1 nM PMID[504082]
NPT397 Cell Line NCI-H460 Homo sapiens GI50 n.a. 0.1 nM PMID[504082]
NPT398 Cell Line UACC-62 Homo sapiens GI50 n.a. 0.1 nM PMID[504082]
NPT308 Cell Line CAKI-1 Homo sapiens GI50 n.a. 0.1 nM PMID[504082]
NPT399 Cell Line SF-295 Homo sapiens GI50 n.a. 0.1 nM PMID[504082]
NPT400 Cell Line MDA-MB-435 Homo sapiens GI50 n.a. 0.1 nM PMID[504082]
NPT458 Cell Line IGROV-1 Homo sapiens GI50 n.a. 0.1 nM PMID[504082]
NPT402 Cell Line Hs-578T Homo sapiens GI50 n.a. 0.1 nM PMID[504082]
NPT401 Cell Line 786-0 Homo sapiens GI50 n.a. 0.1 nM PMID[504082]
NPT404 Cell Line CCRF-CEM Homo sapiens GI50 n.a. 0.1 nM PMID[504082]
NPT139 Cell Line HT-29 Homo sapiens GI50 n.a. 0.1 nM PMID[504082]
NPT405 Cell Line NCI-H226 Homo sapiens GI50 n.a. 0.1 nM PMID[504082]
NPT406 Cell Line RXF 393 Homo sapiens GI50 n.a. 0.1 nM PMID[504082]
NPT407 Cell Line COLO 205 Homo sapiens GI50 n.a. 0.1 nM PMID[504082]
NPT83 Cell Line MCF7 Homo sapiens IC50 = 14.0 nM PMID[504083]
NPT2688 Organism Sus scrofa Sus scrofa Tubulin polymerization = 83.0 % PMID[504078]
NPT2688 Organism Sus scrofa Sus scrofa EC50 = 880.0 nM PMID[504078]
NPT20529 NON-MOLECULAR NON-PROTEIN TARGET n.a. IC50 = 44.0 nM PMID[504081]
NPT518 Protein Complex Tubulin Homo sapiens Inhibition = 43.3 % PMID[504083]
NPT631 Tissue Brain Mus musculus Drug uptake = 111.0 nM PMID[504084]
NPT631 Tissue Brain Mus musculus Drug uptake = 161.0 nM PMID[504084]
NPT624 Tissue Plasma Mus musculus Cp = 19.0 nM PMID[504084]
NPT20555 ORGANISM SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 Inhibition = 2.11 % PMID[504086]
NPT20556 SINGLE PROTEIN Replicase polyprotein 1ab Severe acute respiratory syndrome coronavirus 2 Inhibition = 9.083 % PMID[504087]
NPT20555 ORGANISM SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 Inhibition = -0.06 % PMID[504088]
NPT20555 ORGANISM SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 IC50 > 20000.0 nM PMID[504089]
NPT20555 ORGANISM SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 IC50 > 19952.62 nM PMID[504089]
NPT2 Others Unspecified IC50 = 10 nM PMID[23994325]

☑ 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 NPC185665 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 NPC474094
1.0 High Similarity NPC475737
0.9929 High Similarity NPC32583
0.9929 High Similarity NPC474090
0.9929 High Similarity NPC61667
0.9929 High Similarity NPC252616
0.9929 High Similarity NPC45576
0.9929 High Similarity NPC109498
0.9929 High Similarity NPC163147
0.9929 High Similarity NPC154873
0.9859 High Similarity NPC224609
0.9859 High Similarity NPC268063
0.9858 High Similarity NPC474067
0.9857 High Similarity NPC474064
0.9857 High Similarity NPC474068
0.9857 High Similarity NPC474103
0.9857 High Similarity NPC82436
0.9787 High Similarity NPC474079
0.9787 High Similarity NPC21449
0.9787 High Similarity NPC157194
0.9787 High Similarity NPC474102
0.9787 High Similarity NPC474080
0.9787 High Similarity NPC475683
0.9655 High Similarity NPC127775
0.9653 High Similarity NPC212214
0.9586 High Similarity NPC21126
0.9521 High Similarity NPC474538
0.9521 High Similarity NPC52587
0.9517 High Similarity NPC202591
0.9514 High Similarity NPC474515
0.9514 High Similarity NPC206724
0.9504 High Similarity NPC474069
0.9456 High Similarity NPC231110
0.9392 High Similarity NPC312887
0.8732 High Similarity NPC474070
0.8239 Intermediate Similarity NPC475604
0.8028 Intermediate Similarity NPC475568
0.7378 Intermediate Similarity NPC315252
0.7342 Intermediate Similarity NPC190329
0.7229 Intermediate Similarity NPC186452
0.7215 Intermediate Similarity NPC469801
0.7188 Intermediate Similarity NPC319751
0.7186 Intermediate Similarity NPC211555
0.7059 Intermediate Similarity NPC12660
0.7055 Intermediate Similarity NPC119481
0.7018 Intermediate Similarity NPC54983
0.6994 Remote Similarity NPC473398
0.6782 Remote Similarity NPC101980
0.6782 Remote Similarity NPC470146
0.6782 Remote Similarity NPC97078
0.6494 Remote Similarity NPC522
0.6494 Remote Similarity NPC56058
0.6461 Remote Similarity NPC164006
0.6402 Remote Similarity NPC165538
0.64 Remote Similarity NPC210424
0.6384 Remote Similarity NPC475554
0.6383 Remote Similarity NPC122427
0.6343 Remote Similarity NPC216720
0.6303 Remote Similarity NPC469858
0.6296 Remote Similarity NPC329961
0.6284 Remote Similarity NPC132662
0.6243 Remote Similarity NPC14101
0.6175 Remote Similarity NPC473704
0.6169 Remote Similarity NPC145178
0.6169 Remote Similarity NPC14877
0.6169 Remote Similarity NPC475350
0.6133 Remote Similarity NPC24990
0.612 Remote Similarity NPC134480
0.6078 Remote Similarity NPC251036
0.6022 Remote Similarity NPC161242
0.6022 Remote Similarity NPC473886
0.5936 Remote Similarity NPC475534
0.5936 Remote Similarity NPC476080
0.593 Remote Similarity NPC475390
0.5924 Remote Similarity NPC476103
0.5918 Remote Similarity NPC106235
0.5918 Remote Similarity NPC239660
0.5899 Remote Similarity NPC475196
0.5873 Remote Similarity NPC263485
0.5873 Remote Similarity NPC229160
0.5873 Remote Similarity NPC25316
0.582 Remote Similarity NPC475330
0.5812 Remote Similarity NPC161143
0.5789 Remote Similarity NPC174652
0.5723 Remote Similarity NPC478251
0.5723 Remote Similarity NPC478252
0.5644 Remote Similarity NPC267605
0.5615 Remote Similarity NPC30527

  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 NPC185665 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
1.0 High Similarity NPD6907 Phase 2
0.9586 High Similarity NPD6910 Phase 3
0.932 High Similarity NPD6911 Discontinued
0.9085 High Similarity NPD6916 Clinical (unspecified phase)
0.8497 Intermediate Similarity NPD6915 Approved
0.715 Intermediate Similarity NPD7496 Phase 2
0.6429 Remote Similarity NPD2957 Phase 2
0.6395 Remote Similarity NPD5189 Clinical (unspecified phase)
0.6322 Remote Similarity NPD5634 Approved
0.6196 Remote Similarity NPD1083 Clinical (unspecified phase)
0.6066 Remote Similarity NPD6870 Phase 1
0.5918 Remote Similarity NPD8339 Clinical (unspecified phase)
0.5876 Remote Similarity NPD6348 Clinical (unspecified phase)
0.5744 Remote Similarity NPD6349 Phase 1
0.5684 Remote Similarity NPD6642 Approved
0.5684 Remote Similarity NPD6641 Approved
0.5648 Remote Similarity NPD7977 Clinical (unspecified phase)
0.5606 Remote Similarity NPD4949 Discontinued
0.5604 Remote Similarity NPD8071 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