NPASS Compound

Structure

NPC8325 OpenBabel07101719152D 32 36 0 0 1 0 0 0 0 0999 V2000 -0.5352 -2.5181 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4538 2.3090 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6722 -1.5181 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6831 1.3090 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9890 -1.8271 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 1.6180 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9401 -1.5181 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.9511 1.3090 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.8061 -2.0181 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8171 1.8090 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6722 -0.5181 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 2.6831 0.3090 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.9401 -0.5181 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.9511 0.3090 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.8061 -0.0181 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 1.8171 -0.1910 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.4067 -0.9135 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5823 0.7045 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4013 -1.0181 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.5878 0.8090 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.9890 -0.2091 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 -3.8061 -3.0181 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.8171 2.8090 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.5382 -0.0181 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 3.5491 -0.1910 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.8061 0.9819 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.8171 -1.1910 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.1810 -1.7226 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.1701 1.5135 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.5352 -1.5181 0.0000 S 0 0 0 0 0 0 0 0 0 0 0 0 -1.4538 1.3090 0.0000 S 0 0 0 0 0 0 0 0 0 0 0 0 1 31 1 0 0 0 0 2 32 1 0 0 0 0 3 9 1 0 0 0 0 3 11 1 0 0 0 0 4 10 1 0 0 0 0 4 12 1 0 0 0 0 5 19 1 0 0 0 0 6 20 1 0 0 0 0 7 5 1 1 0 0 0 7 9 1 0 0 0 0 7 13 1 0 0 0 0 8 6 1 1 0 0 0 8 10 1 0 0 0 0 8 14 1 0 0 0 0 9 23 2 0 0 0 0 10 24 2 0 0 0 0 11 15 1 0 0 0 0 11 25 1 6 0 0 0 12 16 1 0 0 0 0 12 26 1 6 0 0 0 13 15 1 0 0 0 0 13 21 1 1 0 0 0 14 16 1 0 0 0 0 14 22 1 1 0 0 0 15 27 1 6 0 0 0 16 28 1 6 0 0 0 17 19 1 0 0 0 0 17 22 1 0 0 0 0 17 29 2 0 0 0 0 18 20 1 0 0 0 0 18 21 1 0 0 0 0 18 30 2 0 0 0 0 19 21 1 0 0 0 0 19 31 1 1 0 0 0 20 22 1 0 0 0 0 20 32 1 1 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	486.11
Volume:	430.481
LogP:	-0.367
LogD:	-0.126
LogS:	-2.145
# Rotatable Bonds:	2
TPSA:	155.68
# H-Bond Aceptor:	10
# H-Bond Donor:	4
# Rings:	5
# Heavy Atoms:	12

MedChem Properties

QED Drug-Likeness Score:	0.342
Synthetic Accessibility Score:	5.586
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:	-5.707
MDCK Permeability:	3.494246584523353e-06
Pgp-inhibitor:	0.264
Pgp-substrate:	0.992
Human Intestinal Absorption (HIA):	0.521
20% Bioavailability (F20%):	0.007
30% Bioavailability (F30%):	0.137

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.019
Plasma Protein Binding (PPB):	61.856117248535156%
Volume Distribution (VD):	0.373
Pgp-substrate:	46.215187072753906%

ADMET: Metabolism

CYP1A2-inhibitor:	0.001
CYP1A2-substrate:	0.083
CYP2C19-inhibitor:	0.014
CYP2C19-substrate:	0.871
CYP2C9-inhibitor:	0.026
CYP2C9-substrate:	0.115
CYP2D6-inhibitor:	0.001
CYP2D6-substrate:	0.048
CYP3A4-inhibitor:	0.016
CYP3A4-substrate:	0.971

ADMET: Excretion

Clearance (CL):	3.128
Half-life (T1/2):	0.888

ADMET: Toxicity

hERG Blockers:	0.001
Human Hepatotoxicity (H-HT):	0.292
Drug-inuced Liver Injury (DILI):	0.987
AMES Toxicity:	0.005
Rat Oral Acute Toxicity:	0.781
Maximum Recommended Daily Dose:	0.017
Skin Sensitization:	0.236
Carcinogencity:	0.19
Eye Corrosion:	0.003
Eye Irritation:	0.007
Respiratory Toxicity:	0.004

Download Data

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

Natural Product: NPC8325

Natural Product ID:	NPC8325
*Common Name:**	Epicoccin H
IUPAC Name:	n.a.
Synonyms:	Epicoccin H
Standard InCHIKey:	KIFUAYSXLVXNEJ-ZHJPTRFQSA-N
Standard InCHI:	InChI=1S/C20H26N2O8S2/c1-31-19-5-7-9(23)3-11(25)15(27)13(7)21(19)18(30)20(32-2)6-8-10(24)4-12(26)16(28)14(8)22(20)17(19)29/h7-8,11-16,25-28H,3-6H2,1-2H3/t7-,8-,11-,12-,13-,14-,15-,16-,19+,20+/m0/s1
SMILES:	CS[C@]12C[C@H]3C(=O)C[C@@H]([C@@H]([C@H]3N2C(=O)[C@@]2(C[C@H]3C(=O)C[C@@H]([C@@H]([C@H]3N2C1=O)O)O)SC)O)O
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL1079828
PubChem CID:	44614254
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]
NPO18557	Epicoccum nigrum	Species	Didymellaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[24328302]
NPO18557	Epicoccum nigrum	Species	Didymellaceae	Eukaryota	n.a.	n.a.	n.a.	Database[Title]
NPO18557	Epicoccum nigrum	Species	Didymellaceae	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
Others	1

Activity Type	# Activity
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	=	42200.0	nM	PMID[490395]
NPT27	Others	Unspecified		CC50	>	100000.0	nM	PMID[490395]

☑ 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 NPC8325 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	254
0.1-0.2	4102
0.2-0.3	20785
0.3-0.4	13991
0.4-0.5	3303
0.5-0.6	229
0.6-0.7	14
0.7-0.8	8
0.8-0.85	2
0.85-0.9	5
0.9-0.95	3
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
0.9187	High Similarity	NPC25327
0.9068	High Similarity	NPC28542
0.8855	High Similarity	NPC469800
0.8731	High Similarity	NPC243412
0.856	High Similarity	NPC211848
0.8347	Intermediate Similarity	NPC309731
0.8217	Intermediate Similarity	NPC220396
0.8031	Intermediate Similarity	NPC266910
0.792	Intermediate Similarity	NPC271115
0.7857	Intermediate Similarity	NPC276822
0.7174	Intermediate Similarity	NPC41162
0.6667	Remote Similarity	NPC88943
0.66	Remote Similarity	NPC956
0.6596	Remote Similarity	NPC262880
0.6596	Remote Similarity	NPC247902
0.6392	Remote Similarity	NPC475342
0.6259	Remote Similarity	NPC17581
0.6259	Remote Similarity	NPC476155
0.6214	Remote Similarity	NPC470788
0.6111	Remote Similarity	NPC97580
0.6047	Remote Similarity	NPC134504
0.6047	Remote Similarity	NPC47076
0.6	Remote Similarity	NPC322966
0.5926	Remote Similarity	NPC241394
0.5852	Remote Similarity	NPC128303
0.5816	Remote Similarity	NPC272166
0.5806	Remote Similarity	NPC277918
0.5743	Remote Similarity	NPC309525
0.5732	Remote Similarity	NPC477401
0.5732	Remote Similarity	NPC477399
0.5714	Remote Similarity	NPC477400
0.5714	Remote Similarity	NPC474210
0.5714	Remote Similarity	NPC82129
0.5694	Remote Similarity	NPC470300
0.5685	Remote Similarity	NPC160688
0.5664	Remote Similarity	NPC66007

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 NPC8325 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	114
0.1-0.2	1647
0.2-0.3	4860
0.3-0.4	2085
0.4-0.5	366
0.5-0.6	76
0.6-0.7	2
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
0.649	Remote Similarity	NPD5193	Discontinued
0.6032	Remote Similarity	NPD2682	Approved
0.6	Remote Similarity	NPD3715	Approved
0.6	Remote Similarity	NPD3713	Approved
0.6	Remote Similarity	NPD3714	Approved
0.5816	Remote Similarity	NPD1000	Clinical (unspecified phase)
0.5693	Remote Similarity	NPD6920	Discontinued

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