NPASS Compound

Structure

CID243412 OpenBabel06191716042D 32 38 0 0 1 0 0 0 0 0999 V2000 2.0301 1.9650 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6952 1.3151 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9239 -0.6027 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3874 -0.2041 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5029 -1.8688 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3886 -0.6324 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 4.0380 -1.1615 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.1479 -0.1744 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9410 -1.4894 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.4057 -1.5191 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 3.5306 -0.4340 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 3.7211 -0.6070 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1822 -1.9474 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 3.4024 -0.1893 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 3.1300 -0.2357 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 3.0900 -0.5091 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 1.8889 -2.0067 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9231 -0.2338 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6649 -1.5785 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 1.1467 -0.6620 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 2.6820 -0.6917 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 1.1296 -1.5488 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -1.1311 0.6931 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 4.2482 0.1590 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.1990 -2.8149 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 3.8149 0.6440 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.8721 -2.8743 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.9399 0.6338 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.4649 0.4142 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.6199 -0.9414 0.0000 S 0 0 0 0 0 0 0 0 0 0 0 0 -1.2790 -0.3427 0.0000 S 0 0 0 0 0 0 0 0 0 0 0 0 -0.0000 -0.0000 0.0000 S 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 0 0 0 2 29 1 0 0 0 0 3 8 1 0 0 0 0 6 4 1 6 0 0 0 6 8 1 0 0 0 0 6 10 1 0 0 0 0 7 5 1 6 0 0 0 7 11 1 0 0 0 0 7 12 1 0 0 0 0 8 23 2 0 0 0 0 9 3 1 1 0 0 0 9 13 1 0 0 0 0 9 31 1 0 0 0 0 10 13 1 0 0 0 0 10 22 1 6 0 0 0 11 14 1 0 0 0 0 11 21 1 6 0 0 0 12 24 2 0 0 0 0 13 25 1 1 0 0 0 14 15 1 0 0 0 0 14 26 1 6 0 0 0 15 16 1 0 0 0 0 15 29 1 6 0 0 0 16 12 1 1 0 0 0 16 30 1 0 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 5 1 6 0 0 0 19 21 1 0 0 0 0 19 30 1 0 0 0 0 20 4 1 1 0 0 0 20 22 1 0 0 0 0 20 32 1 0 0 0 0 31 32 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	498.06
Volume:	423.087
LogP:	0.567
LogD:	0.168
LogS:	-2.167
# Rotatable Bonds:	2
TPSA:	124.45
# H-Bond Aceptor:	9
# H-Bond Donor:	2
# Rings:	7
# Heavy Atoms:	12

MedChem Properties

QED Drug-Likeness Score:	0.477
Synthetic Accessibility Score:	7.608
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:	-5.043
MDCK Permeability:	9.869152563624084e-06
Pgp-inhibitor:	0.379
Pgp-substrate:	0.334
Human Intestinal Absorption (HIA):	0.225
20% Bioavailability (F20%):	0.012
30% Bioavailability (F30%):	0.121

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.013
Plasma Protein Binding (PPB):	64.91498565673828%
Volume Distribution (VD):	0.862
Pgp-substrate:	33.25189208984375%

ADMET: Metabolism

CYP1A2-inhibitor:	0.006
CYP1A2-substrate:	0.089
CYP2C19-inhibitor:	0.088
CYP2C19-substrate:	0.911
CYP2C9-inhibitor:	0.837
CYP2C9-substrate:	0.083
CYP2D6-inhibitor:	0.007
CYP2D6-substrate:	0.051
CYP3A4-inhibitor:	0.182
CYP3A4-substrate:	0.973

ADMET: Excretion

Clearance (CL):	7.098
Half-life (T1/2):	0.689

ADMET: Toxicity

hERG Blockers:	0.004
Human Hepatotoxicity (H-HT):	0.499
Drug-inuced Liver Injury (DILI):	0.998
AMES Toxicity:	0.009
Rat Oral Acute Toxicity:	0.958
Maximum Recommended Daily Dose:	0.037
Skin Sensitization:	0.317
Carcinogencity:	0.741
Eye Corrosion:	0.003
Eye Irritation:	0.006
Respiratory Toxicity:	0.008

Download Data

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

Natural Product: NPC243412

Natural Product ID:	NPC243412
*Common Name:**	Epicoccin S
IUPAC Name:	n.a.
Synonyms:	Epicoccin S
Standard InCHIKey:	CTXSGNLLULNYBQ-IPDYFERDSA-N
Standard InCHI:	InChI=1S/C20H22N2O7S3/c1-2-29-15-14(26)11-7-5-19(30-16(15)12(7)24)17(27)22-10-6-4-20(22,18(28)21(11)19)32-31-9(13(10)25)3-8(6)23/h6-7,9-11,13-16,25-26H,2-5H2,1H3/t6-,7+,9+,10-,11-,13-,14+,15+,16+,19+,20+/m0/s1
SMILES:	CCO[C@@H]1[C@@H]([C@@H]2[C@H]3C[C@]4(C(=O)N5[C@H]6[C@H]7C[C@]5(C(=O)N24)SS[C@H](CC7=O)[C@@H]6O)S[C@@H]1C3=O)O
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL1172227
PubChem CID:	46873163
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]
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]
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]

☑ 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
NON-MOLECULAR	1

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT20529	NON-MOLECULAR	NON-PROTEIN TARGET	n.a.	IC50	=	4950.0	nM	PMID[500756]

☑ 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 NPC243412 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	408
0.1-0.2	5069
0.2-0.3	21844
0.3-0.4	12924
0.4-0.5	2319
0.5-0.6	105
0.6-0.7	11
0.7-0.8	8
0.8-0.85	2
0.85-0.9	3
0.9-0.95	3
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
0.9265	High Similarity	NPC469800
0.8731	High Similarity	NPC8325
0.8657	High Similarity	NPC220396
0.8593	High Similarity	NPC25327
0.8571	High Similarity	NPC211848
0.8045	Intermediate Similarity	NPC28542
0.7941	Intermediate Similarity	NPC266910
0.7687	Intermediate Similarity	NPC309731
0.732	Intermediate Similarity	NPC276822
0.7319	Intermediate Similarity	NPC271115
0.6471	Remote Similarity	NPC41162
0.6456	Remote Similarity	NPC88943
0.6296	Remote Similarity	NPC956
0.6169	Remote Similarity	NPC247902
0.6169	Remote Similarity	NPC262880
0.6023	Remote Similarity	NPC475342
0.5732	Remote Similarity	NPC97580
0.5649	Remote Similarity	NPC476155
0.5649	Remote Similarity	NPC17581
0.5613	Remote Similarity	NPC470788

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 NPC243412 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	165
0.1-0.2	2004
0.2-0.3	4985
0.3-0.4	1734
0.4-0.5	225
0.5-0.6	36
0.6-0.7	1
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
0.6196	Remote Similarity	NPD5193	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