NPASS Compound

Structure

CID266910 OpenBabel06191716072D 30 35 0 0 1 0 0 0 0 0999 V2000 -3.0314 1.9782 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8868 -0.6809 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5077 2.2689 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3631 -0.9716 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4023 1.9782 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 2.2577 -0.6809 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.2168 2.4485 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0722 -1.1512 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0314 1.0376 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 3.8868 0.2597 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.4023 1.0376 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 2.2577 0.2597 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.2168 0.5673 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 3.0722 0.7300 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.9806 1.4096 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1252 -0.1123 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0451 1.5079 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.8103 -0.2106 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.5077 0.7470 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 1.3631 0.5503 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -2.2168 3.3891 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 3.0722 -2.0918 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.2168 -0.3733 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 3.0722 1.6705 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.5334 2.1705 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.6780 -0.8733 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.8460 0.5673 0.0000 S 0 0 0 0 0 0 0 0 0 0 0 0 4.7014 0.7300 0.0000 S 0 0 0 0 0 0 0 0 0 0 0 0 -0.3405 0.7648 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 7 1 0 0 0 0 1 9 1 0 0 0 0 2 8 1 0 0 0 0 2 10 1 0 0 0 0 5 3 1 1 0 0 0 5 7 1 0 0 0 0 5 11 1 0 0 0 0 6 4 1 1 0 0 0 6 8 1 0 0 0 0 6 12 1 0 0 0 0 7 21 2 0 0 0 0 8 22 2 0 0 0 0 9 13 1 0 0 0 0 9 27 1 6 0 0 0 10 14 1 0 0 0 0 10 28 1 6 0 0 0 11 13 1 0 0 0 0 11 19 1 1 0 0 0 12 14 1 0 0 0 0 12 20 1 1 0 0 0 13 23 1 1 0 0 0 14 24 1 1 0 0 0 15 17 1 0 0 0 0 15 20 1 0 0 0 0 15 25 2 0 0 0 0 16 18 1 0 0 0 0 16 19 1 0 0 0 0 16 26 2 0 0 0 0 17 3 1 6 0 0 0 17 19 1 0 0 0 0 17 29 1 0 0 0 0 18 4 1 6 0 0 0 18 20 1 0 0 0 0 18 30 1 0 0 0 0 29 30 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	488.02
Volume:	406.771
LogP:	0.359
LogD:	0.341
LogS:	-3.371
# Rotatable Bonds:	0
TPSA:	115.22
# H-Bond Aceptor:	8
# H-Bond Donor:	2
# Rings:	7
# Heavy Atoms:	12

MedChem Properties

QED Drug-Likeness Score:	0.266
Synthetic Accessibility Score:	7.429
Fsp3:	0.778
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:	-5.388
MDCK Permeability:	5.2245632105041295e-06
Pgp-inhibitor:	0.005
Pgp-substrate:	0.315
Human Intestinal Absorption (HIA):	0.361
20% Bioavailability (F20%):	0.095
30% Bioavailability (F30%):	0.956

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.001
Plasma Protein Binding (PPB):	89.14366149902344%
Volume Distribution (VD):	0.427
Pgp-substrate:	11.130573272705078%

ADMET: Metabolism

CYP1A2-inhibitor:	0.003
CYP1A2-substrate:	0.074
CYP2C19-inhibitor:	0.048
CYP2C19-substrate:	0.879
CYP2C9-inhibitor:	0.685
CYP2C9-substrate:	0.098
CYP2D6-inhibitor:	0.001
CYP2D6-substrate:	0.041
CYP3A4-inhibitor:	0.084
CYP3A4-substrate:	0.968

ADMET: Excretion

Clearance (CL):	7.491
Half-life (T1/2):	0.857

ADMET: Toxicity

hERG Blockers:	0.007
Human Hepatotoxicity (H-HT):	0.809
Drug-inuced Liver Injury (DILI):	0.998
AMES Toxicity:	0.009
Rat Oral Acute Toxicity:	0.909
Maximum Recommended Daily Dose:	0.192
Skin Sensitization:	0.131
Carcinogencity:	0.915
Eye Corrosion:	0.003
Eye Irritation:	0.005
Respiratory Toxicity:	0.002

Download Data

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

Natural Product: NPC266910

Natural Product ID:	NPC266910
*Common Name:**	Rostratin D
IUPAC Name:	n.a.
Synonyms:	Rostratin D
Standard InCHIKey:	GCSPJPVOPHGWRM-XPMVLQEKSA-N
Standard InCHI:	InChI=1S/C18H20N2O6S4/c21-7-1-9(27)13(23)11-5(7)3-17-15(25)20-12-6(8(22)2-10(28)14(12)24)4-18(20,30-29-17)16(26)19(11)17/h5-6,9-14,23-24,27-28H,1-4H2/t5-,6-,9-,10-,11-,12-,13+,14+,17-,18-/m1/s1
SMILES:	O=C1C[C@@H](S)[C@@H]([C@H]2[C@@H]1C[C@@]13N2C(=O)[C@@]2(SS1)N(C3=O)[C@@H]1[C@H](C2)C(=O)C[C@H]([C@@H]1O)S)O
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL515973
PubChem CID:	11488689
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0002389] Diazinanes [CHEMONTID:0000189] Piperazines [CHEMONTID:0001731] Dioxopiperazines [CHEMONTID:0003684] 2,5-dioxopiperazines [CHEMONTID:0001732] Thiodioxopiperazines [CHEMONTID:0001790] Epipolythiodioxopiperazines

*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
NPO30056	Exserohilum rostratum	Species	Pleosporaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[15332857]
NPO30056	Exserohilum rostratum	Species	Pleosporaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[18774863]
NPO30056	Exserohilum rostratum	Species	Pleosporaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[25537529]

☑ 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
NPT393	Cell Line	HCT-116	Homo sapiens	IC50	=	35000.0	nM	PMID[535968]

☑ 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 NPC266910 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	326
0.1-0.2	7225
0.2-0.3	21511
0.3-0.4	11027
0.4-0.5	2410
0.5-0.6	167
0.6-0.7	11
0.7-0.8	10
0.8-0.85	5
0.85-0.9	3
0.9-0.95	1
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
0.9369	High Similarity	NPC309731
0.916	High Similarity	NPC220396
0.8908	High Similarity	NPC211848
0.8793	High Similarity	NPC28542
0.8321	Intermediate Similarity	NPC469800
0.832	Intermediate Similarity	NPC25327
0.8235	Intermediate Similarity	NPC271115
0.8031	Intermediate Similarity	NPC8325
0.7941	Intermediate Similarity	NPC243412
0.7357	Intermediate Similarity	NPC276822
0.7328	Intermediate Similarity	NPC247902
0.7328	Intermediate Similarity	NPC262880
0.6912	Remote Similarity	NPC41162
0.6301	Remote Similarity	NPC88943
0.6271	Remote Similarity	NPC168017
0.6167	Remote Similarity	NPC178632
0.6133	Remote Similarity	NPC956
0.5882	Remote Similarity	NPC272166
0.5878	Remote Similarity	NPC241394
0.5873	Remote Similarity	NPC134504
0.5873	Remote Similarity	NPC47076
0.5845	Remote Similarity	NPC97580
0.582	Remote Similarity	NPC322966
0.5802	Remote Similarity	NPC128303
0.5798	Remote Similarity	NPC124359
0.5781	Remote Similarity	NPC220111
0.5772	Remote Similarity	NPC82129
0.5743	Remote Similarity	NPC475987
0.5743	Remote Similarity	NPC313348
0.5664	Remote Similarity	NPC29326
0.5652	Remote Similarity	NPC475342
0.5643	Remote Similarity	NPC17581
0.5643	Remote Similarity	NPC476155
0.562	Remote Similarity	NPC277918
0.5612	Remote Similarity	NPC66007
0.56	Remote Similarity	NPC312637

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 NPC266910 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	120
0.1-0.2	1983
0.2-0.3	5034
0.3-0.4	1708
0.4-0.5	270
0.5-0.6	33
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
0.625	Remote Similarity	NPD2682	Approved
0.621	Remote Similarity	NPD3715	Approved
0.621	Remote Similarity	NPD3713	Approved
0.621	Remote Similarity	NPD3714	Approved
0.6133	Remote Similarity	NPD5193	Discontinued
0.5882	Remote Similarity	NPD1000	Clinical (unspecified phase)
0.5878	Remote Similarity	NPD6920	Discontinued
0.5659	Remote Similarity	NPD3103	Approved
0.5659	Remote Similarity	NPD3102	Approved
0.5659	Remote Similarity	NPD3104	Approved
0.5659	Remote Similarity	NPD3101	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