NPASS Compound

Structure

NPC474094 OpenBabel07101718222D 37 38 0 0 1 0 0 0 0 0999 V2000 1.3268 -6.5248 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3596 -4.8191 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1625 -4.4927 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8204 -2.2057 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4936 0.0924 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 7.9491 -2.2971 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5000 0.8660 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5000 0.8660 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9848 -5.5851 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 -5.7588 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8508 -5.0851 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8508 -5.0851 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4936 -4.3191 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8356 -3.3794 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4632 -2.7870 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8508 -0.6736 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8864 -3.8594 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9848 -5.5851 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4936 -4.3191 0.0000 C 0 0 3 0 0 0 0 0 0 0 0 0 3.8204 -3.5530 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8356 -2.3794 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.8508 -0.6736 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 7.0503 -2.7355 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.4480 -2.9606 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8356 -3.3794 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.9848 -0.1736 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 2.4936 -1.4397 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4936 -1.4397 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.9848 -0.1736 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 6.1674 -2.2660 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 1.3268 0.7660 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 3.3596 -0.9397 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.3596 -0.9397 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.3268 0.7660 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.8356 -2.3794 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 6.8767 -3.7203 0.0000 S 0 0 0 0 0 0 0 0 0 0 0 0 1 18 1 0 0 0 0 2 19 1 0 0 0 0 3 20 1 0 0 0 0 6 23 1 0 0 0 0 7 30 1 0 0 0 0 8 30 1 0 0 0 0 9 10 1 0 0 0 0 9 11 1 0 0 0 0 10 18 1 0 0 0 0 11 19 1 0 0 0 0 12 13 1 0 0 0 0 12 18 2 0 0 0 0 13 25 1 0 0 0 0 14 19 1 0 0 0 0 14 21 1 0 0 0 0 15 20 2 0 0 0 0 15 24 1 0 0 0 0 16 26 1 0 0 0 0 16 27 1 0 0 0 0 17 24 2 0 0 0 0 17 37 1 0 0 0 0 21 4 1 6 0 0 0 21 28 1 0 0 0 0 22 5 1 1 0 0 0 22 28 1 0 0 0 0 22 29 1 0 0 0 0 23 31 2 0 0 0 0 23 37 1 0 0 0 0 24 31 1 0 0 0 0 25 20 1 6 0 0 0 25 36 1 0 0 0 0 26 30 1 0 0 0 0 26 32 1 1 0 0 0 27 33 2 0 0 0 0 27 36 1 0 0 0 0 28 34 1 6 0 0 0 29 30 1 0 0 0 0 29 35 2 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	533.32
Volume:	567.961
LogP:	4.64
LogD:	4.353
LogS:	-5.287
# 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:	0.342
Synthetic Accessibility Score:	5.003
Fsp3:	0.7
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:	-4.663
MDCK Permeability:	2.602644235594198e-05
Pgp-inhibitor:	0.993
Pgp-substrate:	0.996
Human Intestinal Absorption (HIA):	0.014
20% Bioavailability (F20%):	0.933
30% Bioavailability (F30%):	0.972

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.75
Plasma Protein Binding (PPB):	96.4696044921875%
Volume Distribution (VD):	0.633
Pgp-substrate:	3.3240914344787598%

ADMET: Metabolism

CYP1A2-inhibitor:	0.1
CYP1A2-substrate:	0.318
CYP2C19-inhibitor:	0.388
CYP2C19-substrate:	0.367
CYP2C9-inhibitor:	0.522
CYP2C9-substrate:	0.586
CYP2D6-inhibitor:	0.02
CYP2D6-substrate:	0.448
CYP3A4-inhibitor:	0.77
CYP3A4-substrate:	0.586

ADMET: Excretion

Clearance (CL):	11.427
Half-life (T1/2):	0.109

ADMET: Toxicity

hERG Blockers:	0.045
Human Hepatotoxicity (H-HT):	0.953
Drug-inuced Liver Injury (DILI):	0.852
AMES Toxicity:	0.023
Rat Oral Acute Toxicity:	0.915
Maximum Recommended Daily Dose:	0.942
Skin Sensitization:	0.298
Carcinogencity:	0.82
Eye Corrosion:	0.041
Eye Irritation:	0.011
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: NPC474094

Natural Product ID:	NPC474094
*Common Name:**	Epothilone I3
IUPAC Name:	(4S,7R,8S,9S,15Z,18S)-4,8-dihydroxy-5,5,7,9,11,15-hexamethyl-18-[(E)-1-(2-methyl-1,3-thiazol-4-yl)prop-1-en-2-yl]-1-oxacyclooctadec-15-ene-2,6-dione
Synonyms:	Epothilone I3
Standard InCHIKey:	SHWUXGHQECDXLJ-MUMHOSTJSA-N
Standard InCHI:	InChI=1S/C30H47NO5S/c1-18-10-9-11-19(2)14-21(4)28(34)22(5)29(35)30(7,8)26(32)16-27(33)36-25(13-12-18)20(3)15-24-17-37-23(6)31-24/h12,15,17,19,21-22,25-26,28,32,34H,9-11,13-14,16H2,1-8H3/b18-12-,20-15+/t19?,21-,22+,25-,26-,28-/m0/s1
SMILES:	CC1CCC/C(=CC[C@H](OC(=O)C[C@@H](C(C(=O)[C@@H]([C@H]([C@H](C1)C)O)C)(C)C)O)/C(=C/c1csc(n1)C)/C)/C
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL461280
PubChem CID:	11731174
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	=	0.6	ug.mL-1	PMID[567431]

☑ 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 NPC474094 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	172
0.1-0.2	809
0.2-0.3	3897
0.3-0.4	25500
0.4-0.5	12052
0.5-0.6	196
0.6-0.7	26
0.7-0.8	7
0.8-0.85	1
0.85-0.9	2
0.9-0.95	9
0.95-1	26

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC185665
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 NPC474094 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	132
0.1-0.2	433
0.2-0.3	1717
0.3-0.4	5245
0.4-0.5	1540
0.5-0.6	73
0.6-0.7	5
0.7-0.8	0
0.8-0.85	1
0.85-0.9	1
0.9-0.95	2
0.95-1	1

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