NPASS Compound

Structure

CID25327 OpenBabel06191715352D 32 37 0 0 1 0 0 0 0 0999 V2000 4.8422 0.9223 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7237 -3.9696 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3774 -1.5177 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9857 -2.1350 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7508 -2.0226 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9363 -0.5047 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6263 -1.5173 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.1094 -1.2168 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 3.5020 -2.0229 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8126 -1.4229 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3776 -0.5063 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.4556 -2.6409 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 2.6265 -0.5059 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.5793 -1.7227 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 3.5024 -0.0007 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.7524 -2.4348 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.0004 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0008 -2.0222 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8751 -1.5170 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.8758 -0.5052 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.8753 -0.5056 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -0.8760 -1.5166 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 3.5018 -2.9940 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.5797 -0.6907 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 3.5027 0.9728 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.9853 -3.1670 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.0001 0.9735 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.0011 -2.9957 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 5.2531 -0.0011 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.7061 -3.6714 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.8755 -0.5059 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 29 1 0 0 0 0 2 30 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 29 1 1 0 0 0 12 16 1 0 0 0 0 12 30 1 1 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 25 1 1 0 0 0 16 26 1 1 0 0 0 17 21 1 0 0 0 0 17 27 2 0 0 0 0 18 19 1 0 0 0 0 18 22 1 0 0 0 0 18 28 2 0 0 0 0 19 21 1 0 0 0 0 19 31 1 6 0 0 0 20 17 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:	484.1
Volume:	421.925
LogP:	-0.219
LogD:	0.541
LogS:	-3.195
# Rotatable Bonds:	2
TPSA:	133.68
# H-Bond Aceptor:	10
# H-Bond Donor:	2
# Rings:	7
# Heavy Atoms:	12

MedChem Properties

QED Drug-Likeness Score:	0.466
Synthetic Accessibility Score:	7.08
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:	-4.965
MDCK Permeability:	1.2440372302080505e-05
Pgp-inhibitor:	0.784
Pgp-substrate:	0.408
Human Intestinal Absorption (HIA):	0.83
20% Bioavailability (F20%):	0.096
30% Bioavailability (F30%):	0.972

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.016
Plasma Protein Binding (PPB):	42.96498107910156%
Volume Distribution (VD):	0.395
Pgp-substrate:	48.78329849243164%

ADMET: Metabolism

CYP1A2-inhibitor:	0.002
CYP1A2-substrate:	0.109
CYP2C19-inhibitor:	0.026
CYP2C19-substrate:	0.911
CYP2C9-inhibitor:	0.204
CYP2C9-substrate:	0.045
CYP2D6-inhibitor:	0.002
CYP2D6-substrate:	0.044
CYP3A4-inhibitor:	0.031
CYP3A4-substrate:	0.969

ADMET: Excretion

Clearance (CL):	7.286
Half-life (T1/2):	0.759

ADMET: Toxicity

hERG Blockers:	0.005
Human Hepatotoxicity (H-HT):	0.527
Drug-inuced Liver Injury (DILI):	0.997
AMES Toxicity:	0.011
Rat Oral Acute Toxicity:	0.944
Maximum Recommended Daily Dose:	0.021
Skin Sensitization:	0.424
Carcinogencity:	0.897
Eye Corrosion:	0.003
Eye Irritation:	0.006
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: NPC25327

Natural Product ID:	NPC25327
*Common Name:**	Rostratin C
IUPAC Name:	n.a.
Synonyms:	Rostratin C
Standard InCHIKey:	WZZFRBNMRXVFNQ-UDLXUQTMSA-N
Standard InCHI:	InChI=1S/C20H24N2O8S2/c1-29-11-3-9(23)7-5-19-18(28)22-14-8(10(24)4-12(30-2)16(14)26)6-20(22,32-31-19)17(27)21(19)13(7)15(11)25/h7-8,11-16,25-26H,3-6H2,1-2H3/t7-,8-,11+,12+,13-,14-,15+,16+,19-,20-/m1/s1
SMILES:	CO[C@H]1CC(=O)[C@H]2C[C@@]34C(=O)N5[C@@H]6[C@H](C[C@]5(C(=O)N3[C@H]2[C@H]1O)SS4)C(=O)C[C@@H]([C@@H]6O)OC
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL457599
PubChem CID:	11248709
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	=	1600.0	nM	PMID[519474]

☑ 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 NPC25327 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	307
0.1-0.2	4008
0.2-0.3	19940
0.3-0.4	13044
0.4-0.5	4896
0.5-0.6	459
0.6-0.7	25
0.7-0.8	4
0.8-0.85	8
0.85-0.9	4
0.9-0.95	0
0.95-1	2

Similarity Score	Similarity Level	Natural Product ID
0.9187	High Similarity	NPC8325
0.8814	High Similarity	NPC309731
0.8593	High Similarity	NPC243412
0.8571	High Similarity	NPC469800
0.8361	Intermediate Similarity	NPC271115
0.832	Intermediate Similarity	NPC266910
0.8293	Intermediate Similarity	NPC28542
0.8248	Intermediate Similarity	NPC276822
0.7939	Intermediate Similarity	NPC220396
0.7846	Intermediate Similarity	NPC211848
0.7133	Intermediate Similarity	NPC88943
0.7055	Intermediate Similarity	NPC956
0.6957	Remote Similarity	NPC262880
0.6957	Remote Similarity	NPC247902
0.6573	Remote Similarity	NPC41162
0.6242	Remote Similarity	NPC82129
0.6129	Remote Similarity	NPC322966
0.6047	Remote Similarity	NPC134504
0.6047	Remote Similarity	NPC47076
0.6043	Remote Similarity	NPC272166
0.6026	Remote Similarity	NPC474210
0.5988	Remote Similarity	NPC475342
0.5935	Remote Similarity	NPC477401
0.5935	Remote Similarity	NPC277918
0.5935	Remote Similarity	NPC477399
0.5926	Remote Similarity	NPC241394
0.5921	Remote Similarity	NPC477400
0.592	Remote Similarity	NPC168017
0.5894	Remote Similarity	NPC120420
0.5855	Remote Similarity	NPC99864
0.5852	Remote Similarity	NPC128303
0.585	Remote Similarity	NPC309525
0.5827	Remote Similarity	NPC178632
0.5789	Remote Similarity	NPC313348
0.5789	Remote Similarity	NPC475987
0.5781	Remote Similarity	NPC476019
0.5714	Remote Similarity	NPC473477
0.5714	Remote Similarity	NPC220111
0.5694	Remote Similarity	NPC476155
0.5694	Remote Similarity	NPC17581
0.5685	Remote Similarity	NPC160688
0.5676	Remote Similarity	NPC470650
0.5676	Remote Similarity	NPC470654
0.5676	Remote Similarity	NPC470653
0.5676	Remote Similarity	NPC97580
0.5667	Remote Similarity	NPC212106
0.5664	Remote Similarity	NPC66007
0.5663	Remote Similarity	NPC477398
0.5655	Remote Similarity	NPC470788
0.5605	Remote Similarity	NPC473955

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 NPC25327 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	138
0.1-0.2	1810
0.2-0.3	4777
0.3-0.4	2031
0.4-0.5	321
0.5-0.6	70
0.6-0.7	3
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
0.6939	Remote Similarity	NPD5193	Discontinued
0.6124	Remote Similarity	NPD3714	Approved
0.6124	Remote Similarity	NPD3713	Approved
0.6124	Remote Similarity	NPD3715	Approved
0.6043	Remote Similarity	NPD1000	Clinical (unspecified phase)
0.6032	Remote Similarity	NPD2682	Approved
0.5926	Remote Similarity	NPD6920	Discontinued
0.5855	Remote Similarity	NPD8415	Approved
0.5817	Remote Similarity	NPD8387	Clinical (unspecified phase)
0.5766	Remote Similarity	NPD8307	Discontinued
0.5766	Remote Similarity	NPD8140	Approved
0.5616	Remote Similarity	NPD8346	Approved
0.5616	Remote Similarity	NPD8345	Approved
0.5616	Remote Similarity	NPD8347	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