NPASS Compound

Structure

NPC21449 OpenBabel07101719152D 32 33 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 -3.0529 -2.9740 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0529 -2.9871 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 -1.1241 -2.6165 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 -0.4078 -1.9187 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 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 1 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 -0.0131 -0.9999 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 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 16 1 0 0 0 0 5 19 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 15 1 0 0 0 0 11 22 1 0 0 0 0 12 16 2 0 0 0 0 12 20 1 0 0 0 0 13 21 1 0 0 0 0 13 23 1 0 0 0 0 14 20 2 0 0 0 0 14 32 1 0 0 0 0 15 1 1 6 0 0 0 15 24 1 0 0 0 0 17 3 1 1 0 0 0 17 21 1 0 0 0 0 17 25 1 0 0 0 0 18 4 1 1 0 0 0 18 24 1 0 0 0 0 18 25 1 0 0 0 0 19 26 2 0 0 0 0 19 32 1 0 0 0 0 20 26 1 0 0 0 0 21 27 1 1 0 0 0 22 16 1 6 0 0 0 22 31 1 0 0 0 0 23 28 2 0 0 0 0 23 31 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:	463.24
Volume:	481.481
LogP:	2.791
LogD:	1.747
LogS:	-3.586
# 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:	0.496
Synthetic Accessibility Score:	4.971
Fsp3:	0.64
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:	-4.785
MDCK Permeability:	1.948735734913498e-05
Pgp-inhibitor:	0.008
Pgp-substrate:	0.992
Human Intestinal Absorption (HIA):	0.02
20% Bioavailability (F20%):	0.966
30% Bioavailability (F30%):	0.986

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.391
Plasma Protein Binding (PPB):	87.62430572509766%
Volume Distribution (VD):	0.648
Pgp-substrate:	7.256498336791992%

ADMET: Metabolism

CYP1A2-inhibitor:	0.103
CYP1A2-substrate:	0.341
CYP2C19-inhibitor:	0.1
CYP2C19-substrate:	0.329
CYP2C9-inhibitor:	0.029
CYP2C9-substrate:	0.262
CYP2D6-inhibitor:	0.008
CYP2D6-substrate:	0.383
CYP3A4-inhibitor:	0.558
CYP3A4-substrate:	0.465

ADMET: Excretion

Clearance (CL):	11.271
Half-life (T1/2):	0.704

ADMET: Toxicity

hERG Blockers:	0.047
Human Hepatotoxicity (H-HT):	0.943
Drug-inuced Liver Injury (DILI):	0.934
AMES Toxicity:	0.031
Rat Oral Acute Toxicity:	0.848
Maximum Recommended Daily Dose:	0.364
Skin Sensitization:	0.343
Carcinogencity:	0.599
Eye Corrosion:	0.254
Eye Irritation:	0.018
Respiratory Toxicity:	0.96

Download Data

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

Natural Product: NPC21449

Natural Product ID:	NPC21449
*Common Name:**	Epothilone C2
IUPAC Name:	(4S,5S,7R,8S,9S,13Z,16S)-4,8-dihydroxy-5,7,9-trimethyl-16-[(E)-1-(2-methyl-1,3-thiazol-4-yl)prop-1-en-2-yl]-1-oxacyclohexadec-13-ene-2,6-dione
Synonyms:	Epothilone C2
Standard InCHIKey:	GGEZPMGQYPDHAV-PPIKOIBXSA-N
Standard InCHI:	InChI=1S/C25H37NO5S/c1-15-10-8-6-7-9-11-22(16(2)12-20-14-32-19(5)26-20)31-23(28)13-21(27)17(3)25(30)18(4)24(15)29/h7,9,12,14-15,17-18,21-22,24,27,29H,6,8,10-11,13H2,1-5H3/b9-7-,16-12+/t15-,17-,18+,21-,22-,24-/m0/s1
SMILES:	C[C@H]1CCC/C=CC[C@@H](/C(=C/c2csc(C)n2)/C)OC(=O)C[C@@H]([C@H](C)C(=O)[C@H](C)[C@H]1O)O
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL517398
PubChem CID:	9912250
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[493599]

☑ 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 NPC21449 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	171
0.1-0.2	810
0.2-0.3	3843
0.3-0.4	25733
0.4-0.5	11824
0.5-0.6	239
0.6-0.7	30
0.7-0.8	8
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	NPC474079
1.0	High Similarity	NPC474080
1.0	High Similarity	NPC475683
1.0	High Similarity	NPC474102
1.0	High Similarity	NPC157194
0.9928	High Similarity	NPC474064
0.9928	High Similarity	NPC474103
0.9928	High Similarity	NPC474068
0.9928	High Similarity	NPC82436
0.9858	High Similarity	NPC163147
0.9858	High Similarity	NPC61667
0.9858	High Similarity	NPC32583
0.9858	High Similarity	NPC45576
0.9858	High Similarity	NPC474090
0.9858	High Similarity	NPC252616
0.9858	High Similarity	NPC109498
0.9789	High Similarity	NPC268063
0.9789	High Similarity	NPC224609
0.9787	High Similarity	NPC185665
0.9787	High Similarity	NPC474067
0.9787	High Similarity	NPC474094
0.9787	High Similarity	NPC475737
0.9718	High Similarity	NPC154873
0.9712	High Similarity	NPC474069
0.9586	High Similarity	NPC127775
0.958	High Similarity	NPC474515
0.958	High Similarity	NPC206724
0.9448	High Similarity	NPC212214
0.9448	High Similarity	NPC202591
0.9384	High Similarity	NPC21126
0.932	High Similarity	NPC52587
0.932	High Similarity	NPC474538
0.9257	High Similarity	NPC231110
0.9195	High Similarity	NPC312887
0.8662	High Similarity	NPC474070
0.8429	Intermediate Similarity	NPC475604
0.8214	Intermediate Similarity	NPC475568
0.7531	Intermediate Similarity	NPC315252
0.75	Intermediate Similarity	NPC190329
0.7372	Intermediate Similarity	NPC469801
0.7342	Intermediate Similarity	NPC319751
0.7205	Intermediate Similarity	NPC119481
0.7143	Intermediate Similarity	NPC473398
0.7126	Intermediate Similarity	NPC211555
0.7066	Intermediate Similarity	NPC186452
0.6919	Remote Similarity	NPC97078
0.6919	Remote Similarity	NPC470146
0.6919	Remote Similarity	NPC101980
0.6901	Remote Similarity	NPC12660
0.686	Remote Similarity	NPC54983
0.6532	Remote Similarity	NPC56058
0.6532	Remote Similarity	NPC522
0.6524	Remote Similarity	NPC165538
0.6505	Remote Similarity	NPC122427
0.6437	Remote Similarity	NPC210424
0.6417	Remote Similarity	NPC329961
0.6411	Remote Similarity	NPC469858
0.6379	Remote Similarity	NPC216720
0.6374	Remote Similarity	NPC14101
0.6313	Remote Similarity	NPC164006
0.6281	Remote Similarity	NPC475350
0.6281	Remote Similarity	NPC145178
0.6281	Remote Similarity	NPC14877
0.6257	Remote Similarity	NPC24990
0.6236	Remote Similarity	NPC475554
0.6209	Remote Similarity	NPC473704
0.6188	Remote Similarity	NPC251036
0.6154	Remote Similarity	NPC134480
0.6145	Remote Similarity	NPC473886
0.6141	Remote Similarity	NPC161242
0.6141	Remote Similarity	NPC132662
0.6059	Remote Similarity	NPC475390
0.6054	Remote Similarity	NPC476080
0.6054	Remote Similarity	NPC475534
0.6044	Remote Similarity	NPC476103
0.6031	Remote Similarity	NPC239660
0.6031	Remote Similarity	NPC106235
0.6	Remote Similarity	NPC475196
0.5989	Remote Similarity	NPC25316
0.5989	Remote Similarity	NPC263485
0.5989	Remote Similarity	NPC229160
0.5936	Remote Similarity	NPC475330
0.5926	Remote Similarity	NPC161143
0.5904	Remote Similarity	NPC174652
0.5848	Remote Similarity	NPC478251
0.5848	Remote Similarity	NPC478252
0.573	Remote Similarity	NPC30527
0.5679	Remote Similarity	NPC267605
0.5669	Remote Similarity	NPC201968
0.5641	Remote Similarity	NPC50694
0.5637	Remote Similarity	NPC75498
0.5621	Remote Similarity	NPC329305
0.5619	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 NPC21449 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	424
0.2-0.3	1538
0.3-0.4	5246
0.4-0.5	1704
0.5-0.6	96
0.6-0.7	5
0.7-0.8	0
0.8-0.85	1
0.85-0.9	2
0.9-0.95	1
0.95-1	1

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.9787	High Similarity	NPD6907	Phase 2
0.9384	High Similarity	NPD6910	Phase 3
0.9122	High Similarity	NPD6911	Discontinued
0.8896	High Similarity	NPD6916	Clinical (unspecified phase)
0.8312	Intermediate Similarity	NPD6915	Approved
0.7098	Intermediate Similarity	NPD7496	Phase 2
0.6464	Remote Similarity	NPD2957	Phase 2
0.6337	Remote Similarity	NPD5189	Clinical (unspecified phase)
0.6264	Remote Similarity	NPD5634	Approved
0.6235	Remote Similarity	NPD1083	Clinical (unspecified phase)
0.6031	Remote Similarity	NPD8339	Clinical (unspecified phase)
0.6011	Remote Similarity	NPD6870	Phase 1
0.599	Remote Similarity	NPD6348	Clinical (unspecified phase)
0.5855	Remote Similarity	NPD6349	Phase 1
0.5798	Remote Similarity	NPD6642	Approved
0.5798	Remote Similarity	NPD6641	Approved
0.5759	Remote Similarity	NPD7977	Clinical (unspecified phase)
0.5714	Remote Similarity	NPD4949	Discontinued
0.5707	Remote Similarity	NPD8071	Approved
0.5668	Remote Similarity	NPD6739	Clinical (unspecified phase)
0.5621	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