NPASS Compound

Structure

CID28542 OpenBabel06191715352D 30 34 0 0 1 0 0 0 0 0999 V2000 2.6515 -1.0749 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9665 2.0469 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0531 -0.0010 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8603 -0.5034 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0533 0.9718 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2887 -1.2906 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5267 -0.4867 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9250 1.2736 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3688 -0.0007 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.4969 0.4867 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 4.2111 -0.4870 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4644 0.3852 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2115 1.4581 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.3211 -1.1891 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 3.3690 0.9722 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.9253 -0.3004 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.8418 -0.4863 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8422 1.4588 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6844 -0.0003 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.0002 0.9728 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 1.6846 0.9725 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -0.0000 -0.0000 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 4.2109 -1.4907 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.0638 1.2105 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 4.2117 2.4618 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.7218 -2.0144 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.8416 -1.4900 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.8424 2.4625 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.6842 -0.9730 0.0000 S 0 0 0 0 0 0 0 0 0 0 0 0 0.0004 1.9450 0.0000 S 0 0 0 0 0 0 0 0 0 0 0 0 1 29 1 0 0 0 0 2 30 1 0 0 0 0 3 5 1 0 0 0 0 3 11 1 0 0 0 0 4 6 1 0 0 0 0 4 12 1 0 0 0 0 5 13 1 0 0 0 0 6 14 1 0 0 0 0 7 19 1 0 0 0 0 8 20 1 0 0 0 0 9 7 1 6 0 0 0 9 11 1 0 0 0 0 9 15 1 0 0 0 0 10 8 1 6 0 0 0 10 12 1 0 0 0 0 10 16 1 0 0 0 0 11 23 2 0 0 0 0 12 24 2 0 0 0 0 13 15 1 0 0 0 0 13 25 1 1 0 0 0 14 16 1 0 0 0 0 14 26 1 1 0 0 0 15 21 1 6 0 0 0 16 22 1 6 0 0 0 17 19 1 0 0 0 0 17 22 1 0 0 0 0 17 27 2 0 0 0 0 18 20 1 0 0 0 0 18 21 1 0 0 0 0 18 28 2 0 0 0 0 19 21 1 0 0 0 0 19 29 1 6 0 0 0 20 22 1 0 0 0 0 20 30 1 6 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	454.12
Volume:	412.901
LogP:	-0.24
LogD:	0.594
LogS:	-2.759
# Rotatable Bonds:	2
TPSA:	115.22
# H-Bond Aceptor:	8
# H-Bond Donor:	2
# Rings:	5
# Heavy Atoms:	10

MedChem Properties

QED Drug-Likeness Score:	0.599
Synthetic Accessibility Score:	5.386
Fsp3:	0.8
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:	-5.016
MDCK Permeability:	1.8411494238534942e-05
Pgp-inhibitor:	0.372
Pgp-substrate:	0.579
Human Intestinal Absorption (HIA):	0.223
20% Bioavailability (F20%):	0.006
30% Bioavailability (F30%):	0.011

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.013
Plasma Protein Binding (PPB):	72.08219146728516%
Volume Distribution (VD):	0.547
Pgp-substrate:	38.2628059387207%

ADMET: Metabolism

CYP1A2-inhibitor:	0.001
CYP1A2-substrate:	0.135
CYP2C19-inhibitor:	0.029
CYP2C19-substrate:	0.903
CYP2C9-inhibitor:	0.249
CYP2C9-substrate:	0.119
CYP2D6-inhibitor:	0.001
CYP2D6-substrate:	0.052
CYP3A4-inhibitor:	0.074
CYP3A4-substrate:	0.977

ADMET: Excretion

Clearance (CL):	7.093
Half-life (T1/2):	0.908

ADMET: Toxicity

hERG Blockers:	0.001
Human Hepatotoxicity (H-HT):	0.245
Drug-inuced Liver Injury (DILI):	0.982
AMES Toxicity:	0.006
Rat Oral Acute Toxicity:	0.872
Maximum Recommended Daily Dose:	0.866
Skin Sensitization:	0.402
Carcinogencity:	0.655
Eye Corrosion:	0.003
Eye Irritation:	0.007
Respiratory Toxicity:	0.003

Download Data

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

Natural Product: NPC28542

Natural Product ID:	NPC28542
*Common Name:**	Epicoccin G
IUPAC Name:	n.a.
Synonyms:	Ent-Epicoccin G; Epicoccin G
Standard InCHIKey:	FZVZQZDYZWKKHU-RIJSRGPQSA-N
Standard InCHI:	InChI=1S/C20H26N2O6S2/c1-29-19-7-9-11(23)3-5-13(25)15(9)21(19)18(28)20(30-2)8-10-12(24)4-6-14(26)16(10)22(20)17(19)27/h9-10,13-16,25-26H,3-8H2,1-2H3/t9-,10-,13-,14-,15-,16-,19+,20+/m0/s1
SMILES:	CS[C@@]12C[C@@H]3[C@H](N1C(=O)[C@]1(N(C2=O)[C@@H]2[C@@H](O)CCC(=O)[C@@H]2C1)SC)[C@@H](O)CCC3=O
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL1079829
PubChem CID:	44614134
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000264] Organic acids and derivatives [CHEMONTID:0000265] Carboxylic acids and derivatives [CHEMONTID:0000013] Amino acids, peptides, and analogues [CHEMONTID:0000347] Amino acids and derivatives [CHEMONTID:0000060] Alpha amino acids and derivatives

*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
NPO18557	Epicoccum nigrum	Species	Didymellaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[17711348]
NPO18557	Epicoccum nigrum	Species	Didymellaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[19919067]
NPO18557	Epicoccum nigrum	Species	Didymellaceae	Eukaryota	n.a.	The fungus is isolated from the leaves of L. rhodostegia, collected in June 2007 at Nanning, Guangxi Province, China	2007-JUN	PMID[20550196]
NPO28219	Euphorbia peplus	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[21612217]
NPO18557	Epicoccum nigrum	Species	Didymellaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[24328302]
NPO28219	Euphorbia peplus	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[27203291]
NPO18557	Epicoccum nigrum	Species	Didymellaceae	Eukaryota	n.a.	n.a.	n.a.	Database[Title]
NPO28129	Reticulitermes virginicus	Species	Termitoidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO23676	Fleroya rubrostipulata	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO28219	Euphorbia peplus	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO18557	Epicoccum nigrum	Species	Didymellaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO28114	Peltophorum adnatum	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO23882	Cremastosperma microcarpum	Species	Annonaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO27974	Swertia leduci	Species	Gentianaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO28310	Phacelocarpus labillardieri	Species	Phacelocarpaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO28982	Calliandra confusa	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]

☑ 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
EC50	1
IC50	1
Others	1

Activity Type	# Activity
NON-MOLECULAR	1
Organism	1
Others	1

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT24	Organism	Human immunodeficiency virus 1	Human immunodeficiency virus 1	EC50	=	13500.0	nM	PMID[490190]
NPT27	Others	Unspecified		CC50	>	100000.0	nM	PMID[490190]
NPT20529	NON-MOLECULAR	NON-PROTEIN TARGET	n.a.	IC50	=	3070.0	nM	PMID[490191]

☑ 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 NPC28542 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	169
0.1-0.2	4396
0.2-0.3	21181
0.3-0.4	13769
0.4-0.5	2868
0.5-0.6	274
0.6-0.7	18
0.7-0.8	11
0.8-0.85	6
0.85-0.9	2
0.9-0.95	2
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
0.9386	High Similarity	NPC211848
0.9182	High Similarity	NPC309731
0.9068	High Similarity	NPC8325
0.8983	High Similarity	NPC220396
0.8793	High Similarity	NPC266910
0.8293	Intermediate Similarity	NPC25327
0.8154	Intermediate Similarity	NPC469800
0.8051	Intermediate Similarity	NPC271115
0.8045	Intermediate Similarity	NPC243412
0.7795	Intermediate Similarity	NPC41162
0.7194	Intermediate Similarity	NPC276822
0.7154	Intermediate Similarity	NPC262880
0.7154	Intermediate Similarity	NPC247902
0.6617	Remote Similarity	NPC97580
0.6412	Remote Similarity	NPC476155
0.6412	Remote Similarity	NPC17581
0.6364	Remote Similarity	NPC88943
0.6316	Remote Similarity	NPC475342
0.6198	Remote Similarity	NPC47076
0.6198	Remote Similarity	NPC134504
0.619	Remote Similarity	NPC241394
0.619	Remote Similarity	NPC956
0.6165	Remote Similarity	NPC470300
0.6154	Remote Similarity	NPC322966
0.6119	Remote Similarity	NPC470788
0.6111	Remote Similarity	NPC128303
0.6068	Remote Similarity	NPC168017
0.5966	Remote Similarity	NPC178632
0.5948	Remote Similarity	NPC277918
0.594	Remote Similarity	NPC272166
0.5882	Remote Similarity	NPC475340
0.5872	Remote Similarity	NPC29326
0.5827	Remote Similarity	NPC470592
0.5785	Remote Similarity	NPC476019
0.5785	Remote Similarity	NPC312637
0.5778	Remote Similarity	NPC66007
0.576	Remote Similarity	NPC292819
0.5745	Remote Similarity	NPC309525
0.5726	Remote Similarity	NPC117829
0.5714	Remote Similarity	NPC220111
0.5714	Remote Similarity	NPC82129
0.5703	Remote Similarity	NPC287638
0.5703	Remote Similarity	NPC194750
0.5703	Remote Similarity	NPC233274
0.5685	Remote Similarity	NPC475987
0.5685	Remote Similarity	NPC313348
0.5603	Remote Similarity	NPC470783

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 NPC28542 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	97
0.1-0.2	1432
0.2-0.3	4900
0.3-0.4	2219
0.4-0.5	409
0.5-0.6	87
0.6-0.7	6
0.7-0.8	0
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
0.6609	Remote Similarity	NPD2682	Approved
0.6555	Remote Similarity	NPD3713	Approved
0.6555	Remote Similarity	NPD3715	Approved
0.6555	Remote Similarity	NPD3714	Approved
0.619	Remote Similarity	NPD5193	Discontinued
0.6063	Remote Similarity	NPD6920	Discontinued
0.594	Remote Similarity	NPD1000	Clinical (unspecified phase)
0.5935	Remote Similarity	NPD1784	Approved
0.5897	Remote Similarity	NPD3723	Clinical (unspecified phase)
0.584	Remote Similarity	NPD3102	Approved
0.584	Remote Similarity	NPD3104	Approved
0.584	Remote Similarity	NPD3103	Approved
0.584	Remote Similarity	NPD3101	Approved
0.5804	Remote Similarity	NPD7751	Phase 1
0.5745	Remote Similarity	NPD8041	Phase 2
0.5704	Remote Similarity	NPD7915	Approved
0.5704	Remote Similarity	NPD7916	Approved
0.5669	Remote Similarity	NPD5359	Clinical (unspecified phase)
0.5656	Remote Similarity	NPD4780	Clinical (unspecified phase)
0.5652	Remote Similarity	NPD7517	Approved
0.5652	Remote Similarity	NPD7519	Approved
0.5652	Remote Similarity	NPD7518	Approved
0.5645	Remote Similarity	NPD2636	Clinical (unspecified phase)
0.5645	Remote Similarity	NPD2637	Approved
0.5639	Remote Similarity	NPD4260	Discontinued
0.5603	Remote Similarity	NPD7763	Phase 2
0.5603	Remote Similarity	NPD7762	Phase 2
0.56	Remote Similarity	NPD7841	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