NPASS Compound

Structure

NPC45576 OpenBabel07101719252D 35 36 0 0 1 0 0 0 0 0999 V2000 -3.8204 -2.2057 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 -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 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 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 -2.8356 -3.3794 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 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 -2.8356 -2.3794 0.0000 C 0 0 1 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 -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 2 19 1 0 0 0 0 4 21 1 0 0 0 0 5 28 1 0 0 0 0 6 28 1 0 0 0 0 7 8 1 0 0 0 0 7 9 1 0 0 0 0 8 10 1 0 0 0 0 9 11 1 0 0 0 0 10 12 2 0 0 0 0 11 13 1 0 0 0 0 12 14 1 0 0 0 0 13 18 1 0 0 0 0 14 23 1 0 0 0 0 15 19 2 0 0 0 0 15 22 1 0 0 0 0 16 24 1 0 0 0 0 16 25 1 0 0 0 0 17 22 2 0 0 0 0 17 35 1 0 0 0 0 18 1 1 6 0 0 0 18 26 1 0 0 0 0 20 3 1 1 0 0 0 20 26 1 0 0 0 0 20 27 1 0 0 0 0 21 29 2 0 0 0 0 21 35 1 0 0 0 0 22 29 1 0 0 0 0 23 19 1 6 0 0 0 23 34 1 0 0 0 0 24 28 1 0 0 0 0 24 30 1 1 0 0 0 25 31 2 0 0 0 0 25 34 1 0 0 0 0 26 32 1 6 0 0 0 27 28 1 0 0 0 0 27 33 2 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	505.29
Volume:	533.369
LogP:	3.834
LogD:	3.527
LogS:	-4.529
# 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:	0.398
Synthetic Accessibility Score:	4.801
Fsp3:	0.679
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:	-4.775
MDCK Permeability:	2.895371289923787e-05
Pgp-inhibitor:	0.868
Pgp-substrate:	0.997
Human Intestinal Absorption (HIA):	0.02
20% Bioavailability (F20%):	0.989
30% Bioavailability (F30%):	0.989

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.526
Plasma Protein Binding (PPB):	94.84760284423828%
Volume Distribution (VD):	0.574
Pgp-substrate:	3.8863630294799805%

ADMET: Metabolism

CYP1A2-inhibitor:	0.112
CYP1A2-substrate:	0.377
CYP2C19-inhibitor:	0.426
CYP2C19-substrate:	0.254
CYP2C9-inhibitor:	0.45
CYP2C9-substrate:	0.726
CYP2D6-inhibitor:	0.017
CYP2D6-substrate:	0.542
CYP3A4-inhibitor:	0.863
CYP3A4-substrate:	0.52

ADMET: Excretion

Clearance (CL):	10.364
Half-life (T1/2):	0.394

ADMET: Toxicity

hERG Blockers:	0.094
Human Hepatotoxicity (H-HT):	0.925
Drug-inuced Liver Injury (DILI):	0.74
AMES Toxicity:	0.104
Rat Oral Acute Toxicity:	0.932
Maximum Recommended Daily Dose:	0.92
Skin Sensitization:	0.348
Carcinogencity:	0.871
Eye Corrosion:	0.039
Eye Irritation:	0.012
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: NPC45576

Natural Product ID:	NPC45576
*Common Name:**	Epothilone I1
IUPAC Name:	(4S,7R,8S,9S,15Z,18S)-4,8-dihydroxy-5,5,7,9-tetramethyl-18-[(E)-1-(2-methyl-1,3-thiazol-4-yl)prop-1-en-2-yl]-1-oxacyclooctadec-15-ene-2,6-dione
Synonyms:	Epothilone I1
Standard InCHIKey:	MLQWYAQKRLGGTG-ZBUSTYTQSA-N
Standard InCHI:	InChI=1S/C28H43NO5S/c1-18-13-11-9-7-8-10-12-14-23(19(2)15-22-17-35-21(4)29-22)34-25(31)16-24(30)28(5,6)27(33)20(3)26(18)32/h10,12,15,17-18,20,23-24,26,30,32H,7-9,11,13-14,16H2,1-6H3/b12-10-,19-15+/t18-,20+,23-,24-,26-/m0/s1
SMILES:	C[C@H]1CCCCC/C=CC[C@@H](/C(=C/c2csc(C)n2)/C)OC(=O)C[C@@H](C(C)(C)C(=O)[C@H](C)[C@H]1O)O
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL460233
PubChem CID:	10505737
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	=	0.8	ug.mL-1	PMID[537055]

☑ 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 NPC45576 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	174
0.1-0.2	807
0.2-0.3	3696
0.3-0.4	25074
0.4-0.5	12639
0.5-0.6	232
0.6-0.7	30
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	NPC109498
1.0	High Similarity	NPC474090
1.0	High Similarity	NPC32583
1.0	High Similarity	NPC61667
1.0	High Similarity	NPC163147
1.0	High Similarity	NPC252616
0.993	High Similarity	NPC224609
0.993	High Similarity	NPC268063
0.9929	High Similarity	NPC475737
0.9929	High Similarity	NPC474094
0.9929	High Similarity	NPC185665
0.9929	High Similarity	NPC474067
0.9859	High Similarity	NPC154873
0.9858	High Similarity	NPC474102
0.9858	High Similarity	NPC21449
0.9858	High Similarity	NPC474079
0.9858	High Similarity	NPC475683
0.9858	High Similarity	NPC474080
0.9858	High Similarity	NPC157194
0.9787	High Similarity	NPC82436
0.9787	High Similarity	NPC474064
0.9787	High Similarity	NPC474068
0.9787	High Similarity	NPC474103
0.9724	High Similarity	NPC127775
0.9586	High Similarity	NPC202591
0.9586	High Similarity	NPC212214
0.9574	High Similarity	NPC474069
0.9521	High Similarity	NPC21126
0.9456	High Similarity	NPC474538
0.9456	High Similarity	NPC52587
0.9448	High Similarity	NPC474515
0.9448	High Similarity	NPC206724
0.9392	High Similarity	NPC231110
0.9329	High Similarity	NPC312887
0.8803	High Similarity	NPC474070
0.831	Intermediate Similarity	NPC475604
0.8099	Intermediate Similarity	NPC475568
0.7439	Intermediate Similarity	NPC315252
0.7405	Intermediate Similarity	NPC190329
0.7278	Intermediate Similarity	NPC469801
0.725	Intermediate Similarity	NPC319751
0.7246	Intermediate Similarity	NPC211555
0.7186	Intermediate Similarity	NPC186452
0.7117	Intermediate Similarity	NPC119481
0.7055	Intermediate Similarity	NPC473398
0.7018	Intermediate Similarity	NPC12660
0.6977	Remote Similarity	NPC54983
0.6839	Remote Similarity	NPC101980
0.6839	Remote Similarity	NPC470146
0.6839	Remote Similarity	NPC97078
0.6457	Remote Similarity	NPC56058
0.6457	Remote Similarity	NPC522
0.6455	Remote Similarity	NPC165538
0.6436	Remote Similarity	NPC122427
0.6425	Remote Similarity	NPC164006
0.6364	Remote Similarity	NPC210424
0.6351	Remote Similarity	NPC469858
0.6349	Remote Similarity	NPC329961
0.6348	Remote Similarity	NPC475554
0.6307	Remote Similarity	NPC216720
0.6301	Remote Similarity	NPC14101
0.625	Remote Similarity	NPC132662
0.6219	Remote Similarity	NPC145178
0.6219	Remote Similarity	NPC475350
0.6219	Remote Similarity	NPC14877
0.6188	Remote Similarity	NPC24990
0.6141	Remote Similarity	NPC473704
0.6127	Remote Similarity	NPC251036
0.6087	Remote Similarity	NPC134480
0.6077	Remote Similarity	NPC473886
0.6075	Remote Similarity	NPC161242
0.5989	Remote Similarity	NPC475534
0.5989	Remote Similarity	NPC476080
0.5988	Remote Similarity	NPC475390
0.5978	Remote Similarity	NPC476103
0.5969	Remote Similarity	NPC239660
0.5969	Remote Similarity	NPC106235
0.5945	Remote Similarity	NPC475196
0.5926	Remote Similarity	NPC229160
0.5926	Remote Similarity	NPC25316
0.5926	Remote Similarity	NPC263485
0.5873	Remote Similarity	NPC475330
0.5864	Remote Similarity	NPC161143
0.5842	Remote Similarity	NPC174652
0.578	Remote Similarity	NPC478252
0.578	Remote Similarity	NPC478251
0.5668	Remote Similarity	NPC30527
0.5632	Remote Similarity	NPC160222
0.5632	Remote Similarity	NPC193753
0.561	Remote Similarity	NPC267605
0.5602	Remote Similarity	NPC475455

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 NPC45576 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	134
0.1-0.2	427
0.2-0.3	1593
0.3-0.4	5241
0.4-0.5	1661
0.5-0.6	83
0.6-0.7	5
0.7-0.8	1
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
0.9929	High Similarity	NPD6907	Phase 2
0.9521	High Similarity	NPD6910	Phase 3
0.9257	High Similarity	NPD6911	Discontinued
0.9026	High Similarity	NPD6916	Clinical (unspecified phase)
0.8442	Intermediate Similarity	NPD6915	Approved
0.7202	Intermediate Similarity	NPD7496	Phase 2
0.6453	Remote Similarity	NPD5189	Clinical (unspecified phase)
0.6393	Remote Similarity	NPD2957	Phase 2
0.6379	Remote Similarity	NPD5634	Approved
0.6159	Remote Similarity	NPD1083	Clinical (unspecified phase)
0.612	Remote Similarity	NPD6870	Phase 1
0.5969	Remote Similarity	NPD8339	Clinical (unspecified phase)
0.5928	Remote Similarity	NPD6348	Clinical (unspecified phase)
0.5795	Remote Similarity	NPD6349	Phase 1
0.5737	Remote Similarity	NPD6642	Approved
0.5737	Remote Similarity	NPD6641	Approved
0.5699	Remote Similarity	NPD7977	Clinical (unspecified phase)
0.5657	Remote Similarity	NPD4949	Discontinued
0.5652	Remote Similarity	NPD8071	Approved
0.5608	Remote Similarity	NPD6739	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