NPASS Compound

Structure

NPC211555 OpenBabel07101718222D 33 34 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 4.2611 -4.2118 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 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 3.9521 -3.2608 0.0000 C 0 0 0 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 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 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 7.0006 -3.5346 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 2 17 1 0 0 0 0 4 19 1 0 0 0 0 5 26 1 0 0 0 0 6 26 1 0 0 0 0 7 8 1 0 0 0 0 7 9 1 0 0 0 0 8 10 2 0 0 0 0 9 11 1 0 0 0 0 10 12 1 0 0 0 0 11 16 1 0 0 0 0 12 21 1 0 0 0 0 13 17 2 0 0 0 0 13 20 1 0 0 0 0 14 22 1 0 0 0 0 14 23 1 0 0 0 0 15 20 2 0 0 0 0 15 32 1 0 0 0 0 16 1 1 6 0 0 0 16 24 1 0 0 0 0 18 3 1 1 0 0 0 18 24 1 0 0 0 0 18 25 1 0 0 0 0 19 27 2 0 0 0 0 19 32 1 0 0 0 0 20 27 1 0 0 0 0 21 17 1 6 0 0 0 21 33 1 0 0 0 0 22 26 1 0 0 0 0 22 28 1 1 0 0 0 23 29 2 0 0 0 0 23 33 1 0 0 0 0 24 30 1 6 0 0 0 25 26 1 0 0 0 0 25 31 2 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	461.28
Volume:	489.059
LogP:	2.677
LogD:	2.829
LogS:	-3.88
# Rotatable Bonds:	2
TPSA:	109.86
# H-Bond Aceptor:	7
# H-Bond Donor:	2
# Rings:	2
# Heavy Atoms:	7

MedChem Properties

QED Drug-Likeness Score:	0.496
Synthetic Accessibility Score:	4.953
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:	-4.817
MDCK Permeability:	3.873399691656232e-05
Pgp-inhibitor:	0.852
Pgp-substrate:	0.998
Human Intestinal Absorption (HIA):	0.012
20% Bioavailability (F20%):	0.644
30% Bioavailability (F30%):	0.993

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.73
Plasma Protein Binding (PPB):	94.40079498291016%
Volume Distribution (VD):	2.48
Pgp-substrate:	4.525177001953125%

ADMET: Metabolism

CYP1A2-inhibitor:	0.037
CYP1A2-substrate:	0.24
CYP2C19-inhibitor:	0.048
CYP2C19-substrate:	0.075
CYP2C9-inhibitor:	0.078
CYP2C9-substrate:	0.092
CYP2D6-inhibitor:	0.01
CYP2D6-substrate:	0.571
CYP3A4-inhibitor:	0.468
CYP3A4-substrate:	0.34

ADMET: Excretion

Clearance (CL):	11.742
Half-life (T1/2):	0.755

ADMET: Toxicity

hERG Blockers:	0.108
Human Hepatotoxicity (H-HT):	0.831
Drug-inuced Liver Injury (DILI):	0.665
AMES Toxicity:	0.069
Rat Oral Acute Toxicity:	0.964
Maximum Recommended Daily Dose:	0.916
Skin Sensitization:	0.308
Carcinogencity:	0.914
Eye Corrosion:	0.009
Eye Irritation:	0.011
Respiratory Toxicity:	0.977

Download Data

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

Natural Product: NPC211555

Natural Product ID:	NPC211555
*Common Name:**	Epothilone H1
IUPAC Name:	(4S,7R,8S,9S,13Z,16S)-4,8-dihydroxy-5,5,7,9-tetramethyl-16-[(E)-1-(2-methyl-1,3-oxazol-4-yl)prop-1-en-2-yl]-1-oxacyclohexadec-13-ene-2,6-dione
Synonyms:	Epothilone H1
Standard InCHIKey:	RINOSSPYIGLHTK-QJKGZULSSA-N
Standard InCHI:	InChI=1S/C26H39NO6/c1-16-11-9-7-8-10-12-21(17(2)13-20-15-32-19(4)27-20)33-23(29)14-22(28)26(5,6)25(31)18(3)24(16)30/h8,10,13,15-16,18,21-22,24,28,30H,7,9,11-12,14H2,1-6H3/b10-8-,17-13+/t16-,18+,21-,22-,24-/m0/s1
SMILES:	C[C@H]1CCC/C=CC[C@@H](/C(=C/c2coc(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:	CHEMBL471486
PubChem CID:	9955962
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	=	0.12	ug.mL-1	PMID[495804]

☑ 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 NPC211555 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	207
0.1-0.2	882
0.2-0.3	3795
0.3-0.4	18428
0.4-0.5	18720
0.5-0.6	571
0.6-0.7	44
0.7-0.8	46
0.8-0.85	0
0.85-0.9	0
0.9-0.95	1
0.95-1	3

Similarity Score	Similarity Level	Natural Product ID
0.9932	High Similarity	NPC186452
0.9669	High Similarity	NPC12660
0.9605	High Similarity	NPC54983
0.7904	Intermediate Similarity	NPC30527
0.7778	Intermediate Similarity	NPC475455
0.7458	Intermediate Similarity	NPC314523
0.7458	Intermediate Similarity	NPC58001
0.7246	Intermediate Similarity	NPC32583
0.7246	Intermediate Similarity	NPC252616
0.7246	Intermediate Similarity	NPC45576
0.7246	Intermediate Similarity	NPC474090
0.7246	Intermediate Similarity	NPC109498
0.7246	Intermediate Similarity	NPC163147
0.7246	Intermediate Similarity	NPC61667
0.7234	Intermediate Similarity	NPC476829
0.7202	Intermediate Similarity	NPC224609
0.7202	Intermediate Similarity	NPC268063
0.7186	Intermediate Similarity	NPC475737
0.7186	Intermediate Similarity	NPC474067
0.7186	Intermediate Similarity	NPC474094
0.7186	Intermediate Similarity	NPC185665
0.7143	Intermediate Similarity	NPC154873
0.7135	Intermediate Similarity	NPC231110
0.7126	Intermediate Similarity	NPC21449
0.7126	Intermediate Similarity	NPC474079
0.7126	Intermediate Similarity	NPC474080
0.7126	Intermediate Similarity	NPC475683
0.7126	Intermediate Similarity	NPC474102
0.7126	Intermediate Similarity	NPC157194
0.7093	Intermediate Similarity	NPC312887
0.7076	Intermediate Similarity	NPC127775
0.7066	Intermediate Similarity	NPC474064
0.7066	Intermediate Similarity	NPC82436
0.7066	Intermediate Similarity	NPC474103
0.7066	Intermediate Similarity	NPC474068
0.6959	Remote Similarity	NPC212214
0.6959	Remote Similarity	NPC202591
0.6919	Remote Similarity	NPC21126
0.6886	Remote Similarity	NPC474069
0.6879	Remote Similarity	NPC52587
0.6879	Remote Similarity	NPC474538
0.6842	Remote Similarity	NPC474515
0.6842	Remote Similarity	NPC206724
0.6571	Remote Similarity	NPC476828
0.6507	Remote Similarity	NPC476827
0.6507	Remote Similarity	NPC476831
0.6507	Remote Similarity	NPC476826
0.6493	Remote Similarity	NPC325683
0.6476	Remote Similarity	NPC477219
0.6476	Remote Similarity	NPC476830
0.6447	Remote Similarity	NPC208297
0.6447	Remote Similarity	NPC224395
0.6445	Remote Similarity	NPC37924
0.6415	Remote Similarity	NPC476832
0.6372	Remote Similarity	NPC322800
0.6372	Remote Similarity	NPC168135
0.633	Remote Similarity	NPC477587
0.633	Remote Similarity	NPC477589
0.6326	Remote Similarity	NPC299035
0.6326	Remote Similarity	NPC177432
0.6313	Remote Similarity	NPC295653
0.6313	Remote Similarity	NPC107458
0.6296	Remote Similarity	NPC477218
0.6273	Remote Similarity	NPC477586
0.6273	Remote Similarity	NPC477588
0.6273	Remote Similarity	NPC477585
0.6273	Remote Similarity	NPC477590
0.6268	Remote Similarity	NPC309919
0.6256	Remote Similarity	NPC258022
0.625	Remote Similarity	NPC474070
0.6193	Remote Similarity	NPC88938
0.6193	Remote Similarity	NPC58112
0.6193	Remote Similarity	NPC306300
0.619	Remote Similarity	NPC49195
0.6061	Remote Similarity	NPC46313
0.6061	Remote Similarity	NPC199461
0.6061	Remote Similarity	NPC103452
0.601	Remote Similarity	NPC48323
0.601	Remote Similarity	NPC289029
0.5833	Remote Similarity	NPC475604
0.5783	Remote Similarity	NPC72715
0.5655	Remote Similarity	NPC475568
0.5612	Remote Similarity	NPC475421
0.5611	Remote Similarity	NPC190329
0.5611	Remote Similarity	NPC314633
0.5602	Remote Similarity	NPC209981

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 NPC211555 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	152
0.1-0.2	460
0.2-0.3	1662
0.3-0.4	4270
0.4-0.5	2492
0.5-0.6	103
0.6-0.7	10
0.7-0.8	1
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.7186	Intermediate Similarity	NPD6907	Phase 2
0.7112	Intermediate Similarity	NPD6347	Phase 2
0.6984	Remote Similarity	NPD7490	Discontinued
0.6919	Remote Similarity	NPD6910	Phase 3
0.6821	Remote Similarity	NPD6911	Discontinued
0.6701	Remote Similarity	NPD7896	Approved
0.6611	Remote Similarity	NPD6916	Clinical (unspecified phase)
0.6394	Remote Similarity	NPD6974	Phase 3
0.6359	Remote Similarity	NPD4667	Clinical (unspecified phase)
0.6183	Remote Similarity	NPD6870	Phase 1
0.6139	Remote Similarity	NPD2779	Approved
0.6111	Remote Similarity	NPD6915	Approved
0.607	Remote Similarity	NPD6857	Phase 3
0.6019	Remote Similarity	NPD2433	Clinical (unspecified phase)
0.5991	Remote Similarity	NPD5443	Clinical (unspecified phase)
0.599	Remote Similarity	NPD2778	Approved
0.5972	Remote Similarity	NPD7547	Clinical (unspecified phase)
0.5972	Remote Similarity	NPD1638	Discovery
0.5909	Remote Similarity	NPD4898	Clinical (unspecified phase)
0.5848	Remote Similarity	NPD7853	Phase 2
0.5833	Remote Similarity	NPD7180	Phase 3
0.574	Remote Similarity	NPD1867	Approved
0.574	Remote Similarity	NPD7284	Clinical (unspecified phase)
0.5708	Remote Similarity	NPD2081	Clinical (unspecified phase)
0.5701	Remote Similarity	NPD3945	Discontinued
0.5686	Remote Similarity	NPD5512	Phase 3
0.5674	Remote Similarity	NPD6169	Phase 1
0.5658	Remote Similarity	NPD4394	Clinical (unspecified phase)
0.5656	Remote Similarity	NPD6247	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