NPASS Compound

Structure

NPC202591 OpenBabel07101718312D 33 35 0 0 1 0 0 0 0 0999 V2000 -1.4846 4.1302 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0516 1.4629 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 9.1067 2.4825 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0785 -0.9969 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9026 -0.4305 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9846 4.6322 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0558 4.2616 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9845 4.6191 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6058 2.1145 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9367 1.3714 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9717 2.5792 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9187 -0.4078 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.9907 0.9931 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6605 3.5638 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.0683 1.6451 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 8.1932 2.0758 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.5840 1.9066 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9586 1.5793 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 2.9033 4.2243 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 3.6011 3.5080 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.9188 -0.3947 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 2.8475 -0.0373 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0553 2.6450 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.6978 0.7163 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 7.3271 2.5758 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 0.7109 -1.3729 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 3.3922 -0.8759 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.0334 2.8529 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.5365 0.1717 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 3.5638 0.6605 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 3.8725 4.4705 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 7.9852 1.0976 0.0000 S 0 0 0 0 0 0 0 0 0 0 0 0 3 16 1 0 0 0 0 4 25 1 0 0 0 0 5 25 1 0 0 0 0 6 7 1 0 0 0 0 6 8 1 0 0 0 0 7 14 1 0 0 0 0 9 10 2 0 0 0 0 9 17 1 0 0 0 0 11 18 1 0 0 0 0 12 21 1 0 0 0 0 12 22 1 0 0 0 0 13 17 2 0 0 0 0 13 33 1 0 0 0 0 14 1 1 1 0 0 0 14 23 1 0 0 0 0 15 2 1 6 0 0 0 15 23 1 0 0 0 0 15 24 1 0 0 0 0 16 26 2 0 0 0 0 16 33 1 0 0 0 0 17 26 1 0 0 0 0 18 10 1 1 0 0 0 18 31 1 0 0 0 0 19 8 1 1 0 0 0 19 20 1 0 0 0 0 19 32 1 0 0 0 0 20 11 1 1 0 0 0 20 32 1 0 0 0 0 21 25 1 0 0 0 0 21 27 1 6 0 0 0 22 28 2 0 0 0 0 22 31 1 0 0 0 0 23 29 1 1 0 0 0 24 25 1 0 0 0 0 24 30 2 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	479.23
Volume:	484.352
LogP:	2.935
LogD:	3.081
LogS:	-4.393
# Rotatable Bonds:	2
TPSA:	109.25
# H-Bond Aceptor:	7
# H-Bond Donor:	2
# Rings:	3
# Heavy Atoms:	8

MedChem Properties

QED Drug-Likeness Score:	0.492
Synthetic Accessibility Score:	5.089
Fsp3:	0.72
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:	-4.72
MDCK Permeability:	2.8589829526026733e-05
Pgp-inhibitor:	0.988
Pgp-substrate:	0.993
Human Intestinal Absorption (HIA):	0.015
20% Bioavailability (F20%):	0.273
30% Bioavailability (F30%):	0.984

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.435
Plasma Protein Binding (PPB):	60.13142395019531%
Volume Distribution (VD):	0.388
Pgp-substrate:	18.952926635742188%

ADMET: Metabolism

CYP1A2-inhibitor:	0.054
CYP1A2-substrate:	0.156
CYP2C19-inhibitor:	0.1
CYP2C19-substrate:	0.47
CYP2C9-inhibitor:	0.056
CYP2C9-substrate:	0.186
CYP2D6-inhibitor:	0.009
CYP2D6-substrate:	0.475
CYP3A4-inhibitor:	0.783
CYP3A4-substrate:	0.471

ADMET: Excretion

Clearance (CL):	12.691
Half-life (T1/2):	0.111

ADMET: Toxicity

hERG Blockers:	0.091
Human Hepatotoxicity (H-HT):	0.884
Drug-inuced Liver Injury (DILI):	0.838
AMES Toxicity:	0.124
Rat Oral Acute Toxicity:	0.878
Maximum Recommended Daily Dose:	0.941
Skin Sensitization:	0.332
Carcinogencity:	0.891
Eye Corrosion:	0.039
Eye Irritation:	0.027
Respiratory Toxicity:	0.971

Download Data

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

Natural Product: NPC202591

Natural Product ID:	NPC202591
*Common Name:**	Epothilone A8
IUPAC Name:	(1R,5S,6S,7R,10S,14S,16S)-6,10-dihydroxy-5,7,9,9-tetramethyl-14-[(E)-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-13,17-dioxabicyclo[14.1.0]heptadecane-8,12-dione
Synonyms:	Epothilone A8
Standard InCHIKey:	HQOMWNCHRWPRQE-PAHOANEJSA-N
Standard InCHI:	InChI=1S/C25H37NO6S/c1-14-7-6-8-19-20(32-19)11-18(10-9-17-13-33-16(3)26-17)31-22(28)12-21(27)25(4,5)24(30)15(2)23(14)29/h9-10,13-15,18-21,23,27,29H,6-8,11-12H2,1-5H3/b10-9+/t14-,15+,18+,19+,20-,21-,23-/m0/s1
SMILES:	C[C@H]1CCC[C@@H]2[C@H](C[C@@H](/C=C/c3csc(C)n3)OC(=O)C[C@@H](C(C)(C)C(=O)[C@H](C)[C@H]1O)O)O2
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL512877
PubChem CID:	9913011
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

Activity Type	# Activity
IC50	1

Activity Type	# Activity
Cell Line	1

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT1460	Cell Line	L929	Mus musculus	IC50	=	0.02	ug.mL-1	PMID[497130]

☑ 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 NPC202591 and all remaining natural products in the NPASS database.
● The right table: Most similar natural products (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	182
0.1-0.2	887
0.2-0.3	4441
0.3-0.4	26744
0.4-0.5	10183
0.5-0.6	196
0.6-0.7	22
0.7-0.8	5
0.8-0.85	1
0.85-0.9	0
0.9-0.95	27
0.95-1	9

Similarity Score	Similarity Level	Natural Product ID
0.9861	High Similarity	NPC212214
0.9793	High Similarity	NPC21126
0.9726	High Similarity	NPC474538
0.9726	High Similarity	NPC52587
0.9722	High Similarity	NPC474515
0.9722	High Similarity	NPC206724
0.966	High Similarity	NPC231110
0.9653	High Similarity	NPC474067
0.9595	High Similarity	NPC312887
0.9586	High Similarity	NPC163147
0.9586	High Similarity	NPC45576
0.9586	High Similarity	NPC61667
0.9586	High Similarity	NPC474090
0.9586	High Similarity	NPC32583
0.9586	High Similarity	NPC109498
0.9586	High Similarity	NPC252616
0.9521	High Similarity	NPC268063
0.9521	High Similarity	NPC224609
0.9517	High Similarity	NPC475737
0.9517	High Similarity	NPC474094
0.9517	High Similarity	NPC185665
0.9452	High Similarity	NPC154873
0.9448	High Similarity	NPC157194
0.9448	High Similarity	NPC21449
0.9448	High Similarity	NPC474080
0.9448	High Similarity	NPC475683
0.9448	High Similarity	NPC474102
0.9448	High Similarity	NPC474079
0.9379	High Similarity	NPC82436
0.9379	High Similarity	NPC474103
0.9379	High Similarity	NPC474068
0.9379	High Similarity	NPC474064
0.9329	High Similarity	NPC127775
0.9306	High Similarity	NPC474069
0.8552	High Similarity	NPC474070
0.7945	Intermediate Similarity	NPC475604
0.7862	Intermediate Similarity	NPC475568
0.7246	Intermediate Similarity	NPC315252
0.7205	Intermediate Similarity	NPC190329
0.7188	Intermediate Similarity	NPC469801
0.7135	Intermediate Similarity	NPC12660
0.7093	Intermediate Similarity	NPC54983
0.6959	Remote Similarity	NPC211555
0.6951	Remote Similarity	NPC319751
0.6901	Remote Similarity	NPC186452
0.6826	Remote Similarity	NPC119481
0.6766	Remote Similarity	NPC473398
0.6667	Remote Similarity	NPC470146
0.6667	Remote Similarity	NPC97078
0.6667	Remote Similarity	NPC101980
0.6477	Remote Similarity	NPC522
0.6477	Remote Similarity	NPC56058
0.6354	Remote Similarity	NPC164006
0.6302	Remote Similarity	NPC165538
0.6292	Remote Similarity	NPC210424
0.6283	Remote Similarity	NPC122427
0.6278	Remote Similarity	NPC475554
0.6236	Remote Similarity	NPC216720
0.6215	Remote Similarity	NPC469858
0.6198	Remote Similarity	NPC329961
0.6183	Remote Similarity	NPC132662
0.6162	Remote Similarity	NPC473704
0.6136	Remote Similarity	NPC14101
0.6108	Remote Similarity	NPC134480
0.6033	Remote Similarity	NPC24990
0.6	Remote Similarity	NPC475350
0.6	Remote Similarity	NPC145178
0.6	Remote Similarity	NPC14877
0.5926	Remote Similarity	NPC161242
0.5924	Remote Similarity	NPC473886
0.592	Remote Similarity	NPC475390
0.5913	Remote Similarity	NPC251036
0.5842	Remote Similarity	NPC475534
0.5842	Remote Similarity	NPC476080
0.5829	Remote Similarity	NPC476103
0.5829	Remote Similarity	NPC239660
0.5829	Remote Similarity	NPC106235
0.5781	Remote Similarity	NPC263485
0.5781	Remote Similarity	NPC229160
0.5781	Remote Similarity	NPC25316
0.5747	Remote Similarity	NPC475196
0.5729	Remote Similarity	NPC475330
0.5722	Remote Similarity	NPC161143
0.5699	Remote Similarity	NPC174652
0.5691	Remote Similarity	NPC30527
0.5625	Remote Similarity	NPC478251
0.5625	Remote Similarity	NPC478252

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 NPC202591 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	139
0.1-0.2	454
0.2-0.3	1969
0.3-0.4	5268
0.4-0.5	1261
0.5-0.6	51
0.6-0.7	2
0.7-0.8	1
0.8-0.85	0
0.85-0.9	1
0.9-0.95	2
0.95-1	2

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.9793	High Similarity	NPD6910	Phase 3
0.9524	High Similarity	NPD6911	Discontinued
0.9517	High Similarity	NPD6907	Phase 2
0.9281	High Similarity	NPD6916	Clinical (unspecified phase)
0.8571	High Similarity	NPD6915	Approved
0.7306	Intermediate Similarity	NPD7496	Phase 2
0.6379	Remote Similarity	NPD5189	Clinical (unspecified phase)
0.6307	Remote Similarity	NPD5634	Approved
0.6237	Remote Similarity	NPD2957	Phase 2
0.6031	Remote Similarity	NPD6348	Clinical (unspecified phase)
0.5897	Remote Similarity	NPD6349	Phase 1
0.5893	Remote Similarity	NPD1083	Clinical (unspecified phase)
0.5882	Remote Similarity	NPD6870	Phase 1
0.5829	Remote Similarity	NPD8339	Clinical (unspecified phase)
0.5641	Remote Similarity	NPD7977	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