NPASS Compound

Structure

NPC474515 OpenBabel07101718292D 33 35 0 0 1 0 0 0 0 0999 V2000 -6.0233 -1.1163 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2741 -2.1589 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1693 3.0362 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4563 1.5510 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1351 -0.0967 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 -4.6694 -1.8629 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0529 -2.9740 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6342 -0.4647 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0683 1.6451 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4078 -1.9187 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0191 -1.5861 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.0400 -0.9341 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.9651 -1.2078 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9871 2.0529 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.6322 0.9846 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 4.2215 -0.5035 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6123 -0.6726 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9871 2.0399 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.0529 -2.9871 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.0131 -0.9999 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.1241 -2.6165 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.3706 0.9288 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.0269 0.0658 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.9159 1.6824 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3555 -0.0035 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -1.7792 3.0180 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.4681 1.4734 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.0051 0.2737 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.4605 2.5211 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.2676 -3.6061 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 4.0136 -1.4816 0.0000 S 0 0 0 0 0 0 0 0 0 0 0 0 2 14 1 0 0 0 0 5 17 1 0 0 0 0 6 7 1 0 0 0 0 6 8 1 0 0 0 0 7 13 1 0 0 0 0 9 14 2 0 0 0 0 9 18 1 0 0 0 0 10 19 1 0 0 0 0 10 23 1 0 0 0 0 11 21 1 0 0 0 0 12 18 2 0 0 0 0 12 33 1 0 0 0 0 13 1 1 6 0 0 0 13 24 1 0 0 0 0 15 3 1 6 0 0 0 15 19 1 0 0 0 0 15 25 1 0 0 0 0 16 4 1 1 0 0 0 16 24 1 0 0 0 0 16 25 1 0 0 0 0 17 26 2 0 0 0 0 17 33 1 0 0 0 0 18 26 1 0 0 0 0 19 27 1 1 0 0 0 20 8 1 6 0 0 0 20 22 1 0 0 0 0 20 31 1 0 0 0 0 21 14 1 6 0 0 0 21 32 1 0 0 0 0 22 11 1 6 0 0 0 22 31 1 0 0 0 0 23 28 2 0 0 0 0 23 32 1 0 0 0 0 24 29 1 6 0 0 0 25 30 2 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	479.23
Volume:	484.352
LogP:	2.984
LogD:	1.994
LogS:	-3.279
# 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:	5.162
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:	-4.696
MDCK Permeability:	2.278313877468463e-05
Pgp-inhibitor:	0.45
Pgp-substrate:	0.995
Human Intestinal Absorption (HIA):	0.023
20% Bioavailability (F20%):	0.021
30% Bioavailability (F30%):	0.926

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.322
Plasma Protein Binding (PPB):	63.21546173095703%
Volume Distribution (VD):	1.137
Pgp-substrate:	12.532064437866211%

ADMET: Metabolism

CYP1A2-inhibitor:	0.058
CYP1A2-substrate:	0.34
CYP2C19-inhibitor:	0.032
CYP2C19-substrate:	0.505
CYP2C9-inhibitor:	0.011
CYP2C9-substrate:	0.059
CYP2D6-inhibitor:	0.006
CYP2D6-substrate:	0.111
CYP3A4-inhibitor:	0.161
CYP3A4-substrate:	0.508

ADMET: Excretion

Clearance (CL):	12.774
Half-life (T1/2):	0.073

ADMET: Toxicity

hERG Blockers:	0.075
Human Hepatotoxicity (H-HT):	0.882
Drug-inuced Liver Injury (DILI):	0.947
AMES Toxicity:	0.032
Rat Oral Acute Toxicity:	0.866
Maximum Recommended Daily Dose:	0.757
Skin Sensitization:	0.251
Carcinogencity:	0.366
Eye Corrosion:	0.225
Eye Irritation:	0.025
Respiratory Toxicity:	0.969

Download Data

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

Natural Product: NPC474515

Natural Product ID:	NPC474515
*Common Name:**	Epothilone A1
IUPAC Name:	(1R,5S,6S,7R,9R,10S,14S,16S)-6,10-dihydroxy-5,7,9-trimethyl-14-[(E)-1-(2-methyl-1,3-thiazol-4-yl)prop-1-en-2-yl]-13,17-dioxabicyclo[14.1.0]heptadecane-8,12-dione
Synonyms:	Epothilone A1
Standard InCHIKey:	XBRMHTMQENGRNB-RYTGYZLSSA-N
Standard InCHI:	InChI=1S/C25H37NO6S/c1-13-7-6-8-20-22(31-20)11-21(14(2)9-18-12-33-17(5)26-18)32-23(28)10-19(27)15(3)25(30)16(4)24(13)29/h9,12-13,15-16,19-22,24,27,29H,6-8,10-11H2,1-5H3/b14-9+/t13-,15+,16+,19-,20+,21-,22-,24-/m0/s1
SMILES:	O=C1O[C@@H](C[C@@H]2O[C@@H]2CCC[C@@H]([C@@H]([C@H](C(=O)[C@@H]([C@H](C1)O)C)C)O)C)/C(=C/c1csc(n1)C)/C
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL470479
PubChem CID:	9847978
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[483649]

☑ 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 NPC474515 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	180
0.1-0.2	874
0.2-0.3	4429
0.3-0.4	26932
0.4-0.5	10026
0.5-0.6	191
0.6-0.7	22
0.7-0.8	6
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
1.0	High Similarity	NPC206724
0.986	High Similarity	NPC212214
0.9792	High Similarity	NPC21126
0.9724	High Similarity	NPC474538
0.9724	High Similarity	NPC52587
0.9722	High Similarity	NPC202591
0.9658	High Similarity	NPC231110
0.9648	High Similarity	NPC474103
0.9648	High Similarity	NPC474064
0.9648	High Similarity	NPC474068
0.9648	High Similarity	NPC82436
0.9592	High Similarity	NPC312887
0.958	High Similarity	NPC474080
0.958	High Similarity	NPC475683
0.958	High Similarity	NPC474079
0.958	High Similarity	NPC21449
0.958	High Similarity	NPC157194
0.958	High Similarity	NPC474102
0.9514	High Similarity	NPC475737
0.9514	High Similarity	NPC474094
0.9514	High Similarity	NPC185665
0.9448	High Similarity	NPC474090
0.9448	High Similarity	NPC32583
0.9448	High Similarity	NPC61667
0.9448	High Similarity	NPC45576
0.9448	High Similarity	NPC154873
0.9448	High Similarity	NPC252616
0.9448	High Similarity	NPC109498
0.9448	High Similarity	NPC163147
0.9384	High Similarity	NPC224609
0.9384	High Similarity	NPC268063
0.9379	High Similarity	NPC474067
0.9301	High Similarity	NPC474069
0.9195	High Similarity	NPC127775
0.8288	Intermediate Similarity	NPC474070
0.8056	Intermediate Similarity	NPC475604
0.7847	Intermediate Similarity	NPC475568
0.7333	Intermediate Similarity	NPC315252
0.7296	Intermediate Similarity	NPC190329
0.717	Intermediate Similarity	NPC469801
0.7118	Intermediate Similarity	NPC12660
0.7076	Intermediate Similarity	NPC54983
0.7037	Intermediate Similarity	NPC319751
0.6909	Remote Similarity	NPC119481
0.6882	Remote Similarity	NPC186452
0.6848	Remote Similarity	NPC473398
0.6842	Remote Similarity	NPC211555
0.6743	Remote Similarity	NPC97078
0.6743	Remote Similarity	NPC101980
0.6743	Remote Similarity	NPC470146
0.6552	Remote Similarity	NPC522
0.6552	Remote Similarity	NPC56058
0.6368	Remote Similarity	NPC165538
0.6364	Remote Similarity	NPC210424
0.6349	Remote Similarity	NPC122427
0.6307	Remote Similarity	NPC216720
0.6274	Remote Similarity	NPC469858
0.6263	Remote Similarity	NPC329961
0.6243	Remote Similarity	NPC164006
0.623	Remote Similarity	NPC473704
0.6175	Remote Similarity	NPC134480
0.6167	Remote Similarity	NPC475554
0.6114	Remote Similarity	NPC14101
0.6099	Remote Similarity	NPC24990
0.6075	Remote Similarity	NPC132662
0.6059	Remote Similarity	NPC145178
0.6059	Remote Similarity	NPC475350
0.6059	Remote Similarity	NPC14877
0.5989	Remote Similarity	NPC161242
0.5971	Remote Similarity	NPC251036
0.5904	Remote Similarity	NPC476080
0.5904	Remote Similarity	NPC475534
0.5902	Remote Similarity	NPC473886
0.5896	Remote Similarity	NPC475390
0.5892	Remote Similarity	NPC476103
0.5888	Remote Similarity	NPC239660
0.5888	Remote Similarity	NPC106235
0.5842	Remote Similarity	NPC263485
0.5842	Remote Similarity	NPC229160
0.5842	Remote Similarity	NPC25316
0.5799	Remote Similarity	NPC475196
0.5789	Remote Similarity	NPC475330
0.5781	Remote Similarity	NPC161143
0.5759	Remote Similarity	NPC174652
0.569	Remote Similarity	NPC478251
0.569	Remote Similarity	NPC478252
0.5668	Remote Similarity	NPC30527
0.561	Remote Similarity	NPC267605

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 NPC474515 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	140
0.1-0.2	435
0.2-0.3	1932
0.3-0.4	5291
0.4-0.5	1285
0.5-0.6	59
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
0.9792	High Similarity	NPD6910	Phase 3
0.9521	High Similarity	NPD6911	Discontinued
0.9514	High Similarity	NPD6907	Phase 2
0.9276	High Similarity	NPD6916	Clinical (unspecified phase)
0.8562	High Similarity	NPD6915	Approved
0.7202	Intermediate Similarity	NPD7496	Phase 2
0.6393	Remote Similarity	NPD2957	Phase 2
0.6264	Remote Similarity	NPD5189	Clinical (unspecified phase)
0.6193	Remote Similarity	NPD5634	Approved
0.6094	Remote Similarity	NPD6348	Clinical (unspecified phase)
0.6061	Remote Similarity	NPD1083	Clinical (unspecified phase)
0.5959	Remote Similarity	NPD6349	Phase 1
0.5888	Remote Similarity	NPD8339	Clinical (unspecified phase)
0.5775	Remote Similarity	NPD6870	Phase 1
0.5699	Remote Similarity	NPD7977	Clinical (unspecified phase)
0.5652	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