NPASS Compound

Structure

NPC268063 OpenBabel07101719512D 34 35 0 0 1 0 0 0 0 0999 V2000 -3.0362 -3.1693 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4692 -0.5019 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 8.1221 -2.1497 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6494 0.7604 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3338 0.9426 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0658 -5.0269 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9341 -5.0400 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 1.8629 -4.6694 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6824 -3.9159 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5792 -3.9717 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6212 -2.5176 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 4.2611 -4.2118 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0061 -3.6391 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0529 -2.9871 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.6451 -1.0683 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 7.2086 -2.5564 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9521 -3.2608 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.5994 -2.7255 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9740 -3.0529 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.9999 -0.0131 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 2.6165 -1.1241 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0399 -1.9871 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.9288 -0.3706 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 6.3425 -2.0564 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 3.5920 -4.9550 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.2078 0.9651 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 3.4552 -0.5795 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.0180 -1.7792 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.4734 0.4681 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.9871 -2.0529 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 7.0006 -3.5346 0.0000 S 0 0 0 0 0 0 0 0 0 0 0 0 3 18 1 0 0 0 0 4 26 1 0 0 0 0 5 26 1 0 0 0 0 6 7 1 0 0 0 0 6 8 1 0 0 0 0 7 9 2 0 0 0 0 8 10 1 0 0 0 0 9 11 1 0 0 0 0 10 16 1 0 0 0 0 11 21 1 0 0 0 0 12 19 2 0 0 0 0 12 20 1 0 0 0 0 13 22 1 0 0 0 0 13 23 1 0 0 0 0 14 19 1 0 0 0 0 14 28 1 0 0 0 0 15 20 2 0 0 0 0 15 34 1 0 0 0 0 16 1 1 6 0 0 0 16 24 1 0 0 0 0 17 2 1 1 0 0 0 17 24 1 0 0 0 0 17 25 1 0 0 0 0 18 27 2 0 0 0 0 18 34 1 0 0 0 0 20 27 1 0 0 0 0 21 19 1 6 0 0 0 21 33 1 0 0 0 0 22 26 1 0 0 0 0 22 29 1 1 0 0 0 23 30 2 0 0 0 0 23 33 1 0 0 0 0 24 31 1 6 0 0 0 25 26 1 0 0 0 0 25 32 2 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	493.25
Volume:	507.568
LogP:	2.242
LogD:	2.469
LogS:	-3.976
# Rotatable Bonds:	3
TPSA:	116.95
# H-Bond Aceptor:	7
# H-Bond Donor:	3
# Rings:	2
# Heavy Atoms:	8

MedChem Properties

QED Drug-Likeness Score:	0.432
Synthetic Accessibility Score:	5.04
Fsp3:	0.654
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:	-4.899
MDCK Permeability:	2.3347318347077817e-05
Pgp-inhibitor:	0.178
Pgp-substrate:	0.997
Human Intestinal Absorption (HIA):	0.015
20% Bioavailability (F20%):	0.963
30% Bioavailability (F30%):	0.991

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.477
Plasma Protein Binding (PPB):	64.43885040283203%
Volume Distribution (VD):	0.363
Pgp-substrate:	17.391300201416016%

ADMET: Metabolism

CYP1A2-inhibitor:	0.056
CYP1A2-substrate:	0.102
CYP2C19-inhibitor:	0.053
CYP2C19-substrate:	0.173
CYP2C9-inhibitor:	0.024
CYP2C9-substrate:	0.259
CYP2D6-inhibitor:	0.005
CYP2D6-substrate:	0.17
CYP3A4-inhibitor:	0.547
CYP3A4-substrate:	0.39

ADMET: Excretion

Clearance (CL):	9.746
Half-life (T1/2):	0.857

ADMET: Toxicity

hERG Blockers:	0.036
Human Hepatotoxicity (H-HT):	0.786
Drug-inuced Liver Injury (DILI):	0.87
AMES Toxicity:	0.225
Rat Oral Acute Toxicity:	0.951
Maximum Recommended Daily Dose:	0.942
Skin Sensitization:	0.438
Carcinogencity:	0.936
Eye Corrosion:	0.032
Eye Irritation:	0.021
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: NPC268063

Natural Product ID:	NPC268063
*Common Name:**	Epothilone C9
IUPAC Name:	(4S,7R,8S,9S,13Z,16S)-4,8-dihydroxy-16-[(E)-3-hydroxy-1-(2-methyl-1,3-thiazol-4-yl)prop-1-en-2-yl]-5,5,7,9-tetramethyl-1-oxacyclohexadec-13-ene-2,6-dione
Synonyms:	Epothilone C9
Standard InCHIKey:	RPXWIALRKLAACL-PNJPVOQVSA-N
Standard InCHI:	InChI=1S/C26H39NO6S/c1-16-10-8-6-7-9-11-21(19(14-28)12-20-15-34-18(3)27-20)33-23(30)13-22(29)26(4,5)25(32)17(2)24(16)31/h7,9,12,15-17,21-22,24,28-29,31H,6,8,10-11,13-14H2,1-5H3/b9-7-,19-12+/t16-,17+,21-,22-,24-/m0/s1
SMILES:	OC/C(=Cc1csc(n1)C)/[C@@H]1C/C=CCCC[C@H](C)[C@@H]([C@H](C(=O)C([C@H](CC(=O)O1)O)(C)C)C)O
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL517719
PubChem CID:	10918020
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]

☑ 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	=	0.2	ug.mL-1	PMID[468695]

☑ 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 NPC268063 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	176
0.1-0.2	821
0.2-0.3	3655
0.3-0.4	24562
0.4-0.5	13153
0.5-0.6	254
0.6-0.7	30
0.7-0.8	7
0.8-0.85	2
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	NPC224609
0.993	High Similarity	NPC252616
0.993	High Similarity	NPC32583
0.993	High Similarity	NPC109498
0.993	High Similarity	NPC474090
0.993	High Similarity	NPC154873
0.993	High Similarity	NPC61667
0.993	High Similarity	NPC45576
0.993	High Similarity	NPC163147
0.9859	High Similarity	NPC474067
0.9859	High Similarity	NPC475737
0.9859	High Similarity	NPC185665
0.9859	High Similarity	NPC474094
0.9793	High Similarity	NPC127775
0.9789	High Similarity	NPC474079
0.9789	High Similarity	NPC21449
0.9789	High Similarity	NPC157194
0.9789	High Similarity	NPC474102
0.9789	High Similarity	NPC474080
0.9789	High Similarity	NPC475683
0.9718	High Similarity	NPC474103
0.9718	High Similarity	NPC82436
0.9718	High Similarity	NPC474064
0.9718	High Similarity	NPC474068
0.9524	High Similarity	NPC52587
0.9521	High Similarity	NPC202591
0.9521	High Similarity	NPC212214
0.9507	High Similarity	NPC474069
0.9456	High Similarity	NPC21126
0.9392	High Similarity	NPC474538
0.9384	High Similarity	NPC206724
0.9384	High Similarity	NPC474515
0.9329	High Similarity	NPC231110
0.9267	High Similarity	NPC312887
0.8873	High Similarity	NPC474070
0.838	Intermediate Similarity	NPC475604
0.8169	Intermediate Similarity	NPC475568
0.75	Intermediate Similarity	NPC315252
0.7468	Intermediate Similarity	NPC190329
0.7312	Intermediate Similarity	NPC319751
0.7233	Intermediate Similarity	NPC469801
0.7202	Intermediate Similarity	NPC211555
0.7178	Intermediate Similarity	NPC119481
0.7143	Intermediate Similarity	NPC186452
0.7117	Intermediate Similarity	NPC473398
0.6977	Remote Similarity	NPC12660
0.6936	Remote Similarity	NPC54983
0.6897	Remote Similarity	NPC97078
0.6897	Remote Similarity	NPC101980
0.6897	Remote Similarity	NPC470146
0.6508	Remote Similarity	NPC165538
0.6489	Remote Similarity	NPC122427
0.648	Remote Similarity	NPC164006
0.642	Remote Similarity	NPC56058
0.642	Remote Similarity	NPC522
0.6402	Remote Similarity	NPC329961
0.6328	Remote Similarity	NPC210424
0.6321	Remote Similarity	NPC469858
0.6313	Remote Similarity	NPC475554
0.6304	Remote Similarity	NPC132662
0.6271	Remote Similarity	NPC216720
0.6269	Remote Similarity	NPC475350
0.6269	Remote Similarity	NPC14877
0.6269	Remote Similarity	NPC145178
0.6264	Remote Similarity	NPC14101
0.6243	Remote Similarity	NPC24990
0.6176	Remote Similarity	NPC251036
0.6129	Remote Similarity	NPC161242
0.6108	Remote Similarity	NPC473704
0.6054	Remote Similarity	NPC134480
0.6047	Remote Similarity	NPC475390
0.6044	Remote Similarity	NPC473886
0.6043	Remote Similarity	NPC476080
0.6043	Remote Similarity	NPC475534
0.6033	Remote Similarity	NPC476103
0.5979	Remote Similarity	NPC263485
0.5979	Remote Similarity	NPC229160
0.5979	Remote Similarity	NPC25316
0.5939	Remote Similarity	NPC239660
0.5939	Remote Similarity	NPC106235
0.5926	Remote Similarity	NPC475330
0.5917	Remote Similarity	NPC475196
0.5895	Remote Similarity	NPC174652
0.5833	Remote Similarity	NPC161143
0.5747	Remote Similarity	NPC478251
0.5747	Remote Similarity	NPC478252
0.569	Remote Similarity	NPC193753
0.569	Remote Similarity	NPC160222
0.5671	Remote Similarity	NPC267605
0.5654	Remote Similarity	NPC475455
0.5638	Remote Similarity	NPC30527
0.5631	Remote Similarity	NPC75498
0.5612	Remote Similarity	NPC96016

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 NPC268063 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	137
0.1-0.2	438
0.2-0.3	1588
0.3-0.4	5194
0.4-0.5	1698
0.5-0.6	85
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
0.9859	High Similarity	NPD6907	Phase 2
0.9456	High Similarity	NPD6910	Phase 3
0.9195	High Similarity	NPD6911	Discontinued
0.8968	High Similarity	NPD6916	Clinical (unspecified phase)
0.8387	Intermediate Similarity	NPD6915	Approved
0.7165	Intermediate Similarity	NPD7496	Phase 2
0.6448	Remote Similarity	NPD2957	Phase 2
0.6416	Remote Similarity	NPD5189	Clinical (unspecified phase)
0.6343	Remote Similarity	NPD5634	Approved
0.622	Remote Similarity	NPD1083	Clinical (unspecified phase)
0.6087	Remote Similarity	NPD6870	Phase 1
0.5979	Remote Similarity	NPD6348	Clinical (unspecified phase)
0.5939	Remote Similarity	NPD8339	Clinical (unspecified phase)
0.5846	Remote Similarity	NPD6349	Phase 1
0.5789	Remote Similarity	NPD6641	Approved
0.5789	Remote Similarity	NPD6642	Approved
0.567	Remote Similarity	NPD7977	Clinical (unspecified phase)
0.5628	Remote Similarity	NPD4949	Discontinued
0.5625	Remote Similarity	NPD8071	Approved
0.5613	Remote Similarity	NPD6413	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