NPASS Compound

Structure

NPC474069 OpenBabel07101719242D 27 28 0 0 1 0 0 0 0 0999 V2000 -5.3589 0.1424 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6353 2.3713 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1631 -0.0967 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1275 -2.5715 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1493 -2.7794 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9185 -1.9598 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1778 -2.5424 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3658 -1.0654 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4054 -1.9072 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6622 -0.4647 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9931 -1.2078 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2384 1.5061 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0471 -1.5861 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3808 -0.0655 0.0000 C 0 0 3 0 0 0 0 0 0 0 0 0 -3.1880 1.4769 0.0000 C 0 0 3 0 0 0 0 0 0 0 0 0 4.2496 -0.5034 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6404 -0.6726 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0150 -0.9999 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.2165 1.7140 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.4473 0.8944 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9604 0.8418 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3835 -0.0034 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -2.2315 2.7139 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.3251 1.5295 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.7515 1.4535 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 0.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 4.0416 -1.4816 0.0000 S 0 0 0 0 0 0 0 0 0 0 0 0 1 14 1 0 0 0 0 2 15 1 0 0 0 0 3 16 1 0 0 0 0 4 5 1 0 0 0 0 4 6 1 0 0 0 0 5 7 2 0 0 0 0 6 8 1 0 0 0 0 7 9 1 0 0 0 0 8 14 1 0 0 0 0 9 18 1 0 0 0 0 10 11 2 0 0 0 0 10 17 1 0 0 0 0 12 19 1 0 0 0 0 12 20 1 0 0 0 0 13 17 2 0 0 0 0 13 27 1 0 0 0 0 14 21 1 0 0 0 0 15 19 1 0 0 0 0 15 21 1 0 0 0 0 16 22 2 0 0 0 0 16 27 1 0 0 0 0 17 22 1 0 0 0 0 18 11 1 6 0 0 0 18 26 1 0 0 0 0 19 23 1 1 0 0 0 20 24 2 0 0 0 0 20 26 1 0 0 0 0 21 25 2 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	391.18
Volume:	403.507
LogP:	2.255
LogD:	1.145
LogS:	-3.382
# Rotatable Bonds:	2
TPSA:	76.49
# H-Bond Aceptor:	5
# H-Bond Donor:	1
# Rings:	2
# Heavy Atoms:	6

MedChem Properties

QED Drug-Likeness Score:	0.607
Synthetic Accessibility Score:	4.714
Fsp3:	0.571
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:	-4.785
MDCK Permeability:	2.2213000193005428e-05
Pgp-inhibitor:	0.003
Pgp-substrate:	0.236
Human Intestinal Absorption (HIA):	0.015
20% Bioavailability (F20%):	0.995
30% Bioavailability (F30%):	0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.269
Plasma Protein Binding (PPB):	68.91105651855469%
Volume Distribution (VD):	0.505
Pgp-substrate:	18.165241241455078%

ADMET: Metabolism

CYP1A2-inhibitor:	0.499
CYP1A2-substrate:	0.466
CYP2C19-inhibitor:	0.617
CYP2C19-substrate:	0.306
CYP2C9-inhibitor:	0.217
CYP2C9-substrate:	0.912
CYP2D6-inhibitor:	0.031
CYP2D6-substrate:	0.864
CYP3A4-inhibitor:	0.866
CYP3A4-substrate:	0.42

ADMET: Excretion

Clearance (CL):	10.898
Half-life (T1/2):	0.811

ADMET: Toxicity

hERG Blockers:	0.05
Human Hepatotoxicity (H-HT):	0.938
Drug-inuced Liver Injury (DILI):	0.891
AMES Toxicity:	0.047
Rat Oral Acute Toxicity:	0.344
Maximum Recommended Daily Dose:	0.49
Skin Sensitization:	0.726
Carcinogencity:	0.82
Eye Corrosion:	0.11
Eye Irritation:	0.064
Respiratory Toxicity:	0.922

Download Data

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

Natural Product: NPC474069

Natural Product ID:	NPC474069
*Common Name:**	Epothilone K
IUPAC Name:	(4S,11Z,14S)-4-hydroxy-5,7-dimethyl-14-[(E)-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-1-oxacyclotetradec-11-ene-2,6-dione
Synonyms:	Epothilone K
Standard InCHIKey:	OAXHQZGPHDPLOS-QHPKQRFUSA-N
Standard InCHI:	InChI=1S/C21H29NO4S/c1-14-8-6-4-5-7-9-18(11-10-17-13-27-16(3)22-17)26-20(24)12-19(23)15(2)21(14)25/h5,7,10-11,13-15,18-19,23H,4,6,8-9,12H2,1-3H3/b7-5-,11-10+/t14?,15?,18-,19-/m0/s1
SMILES:	CC1CCCC=CCC(OC(=O)CC(C(C1=O)C)O)C=CC2=CSC(=N2)C
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL459823
PubChem CID:	44559967
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	=	0.3	ug.mL-1	PMID[511515]

☑ 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 NPC474069 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	155
0.1-0.2	837
0.2-0.3	4470
0.3-0.4	27765
0.4-0.5	9237
0.5-0.6	156
0.6-0.7	32
0.7-0.8	6
0.8-0.85	2
0.85-0.9	6
0.9-0.95	7
0.95-1	24

Similarity Score	Similarity Level	Natural Product ID
0.9712	High Similarity	NPC475683
0.9712	High Similarity	NPC474079
0.9712	High Similarity	NPC474102
0.9712	High Similarity	NPC157194
0.9712	High Similarity	NPC474080
0.9712	High Similarity	NPC21449
0.9643	High Similarity	NPC474067
0.964	High Similarity	NPC474064
0.964	High Similarity	NPC474068
0.964	High Similarity	NPC474103
0.964	High Similarity	NPC82436
0.9574	High Similarity	NPC32583
0.9574	High Similarity	NPC45576
0.9574	High Similarity	NPC109498
0.9574	High Similarity	NPC163147
0.9574	High Similarity	NPC61667
0.9574	High Similarity	NPC474090
0.9574	High Similarity	NPC252616
0.9507	High Similarity	NPC224609
0.9507	High Similarity	NPC268063
0.9504	High Similarity	NPC185665
0.9504	High Similarity	NPC475737
0.9504	High Similarity	NPC474094
0.9437	High Similarity	NPC154873
0.931	High Similarity	NPC127775
0.9306	High Similarity	NPC202591
0.9301	High Similarity	NPC206724
0.9301	High Similarity	NPC474515
0.9172	High Similarity	NPC212214
0.911	High Similarity	NPC21126
0.9048	High Similarity	NPC474538
0.9048	High Similarity	NPC52587
0.8986	High Similarity	NPC231110
0.8926	High Similarity	NPC312887
0.8777	High Similarity	NPC474070
0.854	High Similarity	NPC475604
0.8456	Intermediate Similarity	NPC475568
0.761	Intermediate Similarity	NPC315252
0.7582	Intermediate Similarity	NPC190329
0.7451	Intermediate Similarity	NPC469801
0.7308	Intermediate Similarity	NPC319751
0.717	Intermediate Similarity	NPC119481
0.7107	Intermediate Similarity	NPC473398
0.6886	Remote Similarity	NPC211555
0.6826	Remote Similarity	NPC186452
0.6686	Remote Similarity	NPC470146
0.6686	Remote Similarity	NPC97078
0.6686	Remote Similarity	NPC101980
0.6667	Remote Similarity	NPC12660
0.6628	Remote Similarity	NPC54983
0.6527	Remote Similarity	NPC14101
0.6491	Remote Similarity	NPC210424
0.6486	Remote Similarity	NPC165538
0.6467	Remote Similarity	NPC122427
0.6433	Remote Similarity	NPC216720
0.6395	Remote Similarity	NPC522
0.6395	Remote Similarity	NPC56058
0.6378	Remote Similarity	NPC329961
0.6364	Remote Similarity	NPC164006
0.6307	Remote Similarity	NPC24990
0.6286	Remote Similarity	NPC475554
0.6257	Remote Similarity	NPC473704
0.6244	Remote Similarity	NPC14877
0.6244	Remote Similarity	NPC475350
0.6244	Remote Similarity	NPC145178
0.622	Remote Similarity	NPC469858
0.6201	Remote Similarity	NPC134480
0.6193	Remote Similarity	NPC473886
0.6188	Remote Similarity	NPC132662
0.615	Remote Similarity	NPC251036
0.6108	Remote Similarity	NPC475390
0.6099	Remote Similarity	NPC161242
0.6011	Remote Similarity	NPC475534
0.6011	Remote Similarity	NPC476080
0.6	Remote Similarity	NPC476103
0.599	Remote Similarity	NPC239660
0.599	Remote Similarity	NPC106235
0.5962	Remote Similarity	NPC475196
0.5946	Remote Similarity	NPC229160
0.5946	Remote Similarity	NPC25316
0.5946	Remote Similarity	NPC263485
0.5892	Remote Similarity	NPC475330
0.5882	Remote Similarity	NPC161143
0.586	Remote Similarity	NPC174652
0.5799	Remote Similarity	NPC478251
0.5799	Remote Similarity	NPC478252
0.5723	Remote Similarity	NPC267605
0.5667	Remote Similarity	NPC329305
0.5629	Remote Similarity	NPC190955

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 NPC474069 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	126
0.1-0.2	445
0.2-0.3	1550
0.3-0.4	5335
0.4-0.5	1603
0.5-0.6	81
0.6-0.7	5
0.7-0.8	1
0.8-0.85	0
0.85-0.9	2
0.9-0.95	1
0.95-1	1

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.9504	High Similarity	NPD6907	Phase 2
0.911	High Similarity	NPD6910	Phase 3
0.8851	High Similarity	NPD6911	Discontinued
0.8636	High Similarity	NPD6916	Clinical (unspecified phase)
0.8052	Intermediate Similarity	NPD6915	Approved
0.6891	Remote Similarity	NPD7496	Phase 2
0.6517	Remote Similarity	NPD2957	Phase 2
0.6391	Remote Similarity	NPD5189	Clinical (unspecified phase)
0.6316	Remote Similarity	NPD5634	Approved
0.6289	Remote Similarity	NPD1083	Clinical (unspecified phase)
0.599	Remote Similarity	NPD8339	Clinical (unspecified phase)
0.5947	Remote Similarity	NPD6348	Clinical (unspecified phase)
0.5812	Remote Similarity	NPD6349	Phase 1
0.5792	Remote Similarity	NPD6870	Phase 1
0.5751	Remote Similarity	NPD4949	Discontinued
0.5714	Remote Similarity	NPD7977	Clinical (unspecified phase)
0.5707	Remote Similarity	NPD6739	Clinical (unspecified phase)
0.5667	Remote Similarity	NPD6413	Approved
0.5665	Remote Similarity	NPD8071	Approved
0.5622	Remote Similarity	NPD647	Approved
0.5602	Remote Similarity	NPD2306	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