NPASS Compound

Structure

CID271115 OpenBabel06191716072D 28 33 0 0 1 0 0 0 0 0999 V2000 3.2286 -2.1068 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1396 0.7252 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2286 -1.1051 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1396 -0.2765 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5407 -2.4164 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4518 1.0348 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4935 -2.1068 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.4045 0.7252 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 2.3610 -2.6077 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.2720 1.2261 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 2.3610 -0.6042 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.2720 -0.7774 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 1.4935 -1.1051 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.4045 -0.2765 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.0443 -1.5013 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1333 0.1196 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0481 -1.6060 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.8630 0.2243 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.5407 -0.7955 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -1.4518 -0.5861 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 2.3610 -3.6095 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.2720 2.2278 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.3610 0.3975 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.2720 -1.7792 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.6331 -2.3117 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.7221 0.9300 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.3627 -0.8146 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 3 1 0 0 0 0 1 9 1 0 0 0 0 2 4 1 0 0 0 0 2 10 1 0 0 0 0 3 11 1 0 0 0 0 4 12 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 21 1 6 0 0 0 10 22 1 6 0 0 0 11 13 1 0 0 0 0 11 23 1 1 0 0 0 12 14 1 0 0 0 0 12 24 1 1 0 0 0 13 19 1 6 0 0 0 14 20 1 6 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 5 1 6 0 0 0 17 19 1 0 0 0 0 17 27 1 0 0 0 0 18 6 1 6 0 0 0 18 20 1 0 0 0 0 18 28 1 0 0 0 0 27 28 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	428.11
Volume:	375.025
LogP:	0.03
LogD:	0.806
LogS:	-3.603
# Rotatable Bonds:	0
TPSA:	121.54
# H-Bond Aceptor:	8
# H-Bond Donor:	4
# Rings:	7
# Heavy Atoms:	10

MedChem Properties

QED Drug-Likeness Score:	0.372
Synthetic Accessibility Score:	6.925
Fsp3:	0.889
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:	-5.788
MDCK Permeability:	1.144861653301632e-05
Pgp-inhibitor:	0.034
Pgp-substrate:	0.013
Human Intestinal Absorption (HIA):	0.929
20% Bioavailability (F20%):	0.012
30% Bioavailability (F30%):	0.955

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.084
Plasma Protein Binding (PPB):	42.84748840332031%
Volume Distribution (VD):	0.739
Pgp-substrate:	58.92274475097656%

ADMET: Metabolism

CYP1A2-inhibitor:	0.011
CYP1A2-substrate:	0.088
CYP2C19-inhibitor:	0.081
CYP2C19-substrate:	0.891
CYP2C9-inhibitor:	0.549
CYP2C9-substrate:	0.16
CYP2D6-inhibitor:	0.002
CYP2D6-substrate:	0.049
CYP3A4-inhibitor:	0.056
CYP3A4-substrate:	0.976

ADMET: Excretion

Clearance (CL):	11.069
Half-life (T1/2):	0.445

ADMET: Toxicity

hERG Blockers:	0.012
Human Hepatotoxicity (H-HT):	0.391
Drug-inuced Liver Injury (DILI):	0.987
AMES Toxicity:	0.012
Rat Oral Acute Toxicity:	0.077
Maximum Recommended Daily Dose:	0.925
Skin Sensitization:	0.795
Carcinogencity:	0.84
Eye Corrosion:	0.003
Eye Irritation:	0.013
Respiratory Toxicity:	0.036

Download Data

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

Natural Product: NPC271115

Natural Product ID:	NPC271115
*Common Name:**	Rostratin A
IUPAC Name:	n.a.
Synonyms:	Rostratin A
Standard InCHIKey:	UJDXMQJEYGMBMN-FQPNBHNHSA-N
Standard InCHI:	InChI=1S/C18H24N2O6S2/c21-9-1-3-11(23)13-7(9)5-17-15(25)20-14-8(10(22)2-4-12(14)24)6-18(20,28-27-17)16(26)19(13)17/h7-14,21-24H,1-6H2/t7-,8-,9+,10+,11+,12+,13+,14+,17-,18-/m1/s1
SMILES:	C1C[C@@H]([C@@H]2[C@H](C[C@@]34C(=O)N5[C@H]6[C@H](C[C@]5(C(=O)N23)SS4)[C@H](CC[C@@H]6O)O)[C@H]1O)O
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL462959
PubChem CID:	11293291
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]
NPO18557	Epicoccum nigrum	Species	Didymellaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[17711348]
NPO30056	Exserohilum rostratum	Species	Pleosporaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[18774863]
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]
NPO33508	Phoma sp. OUCMDZ-1847	Species	Didymellaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[24370114]
NPO30056	Exserohilum rostratum	Species	Pleosporaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[25537529]
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]
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]
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]

☑ 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	=	9000.0	nM	PMID[551410]

☑ 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 NPC271115 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	286
0.1-0.2	4723
0.2-0.3	21411
0.3-0.4	11690
0.4-0.5	4211
0.5-0.6	339
0.6-0.7	18
0.7-0.8	14
0.8-0.85	3
0.85-0.9	1
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
0.875	High Similarity	NPC309731
0.8361	Intermediate Similarity	NPC25327
0.8235	Intermediate Similarity	NPC266910
0.8051	Intermediate Similarity	NPC28542
0.792	Intermediate Similarity	NPC8325
0.784	Intermediate Similarity	NPC220396
0.7669	Intermediate Similarity	NPC469800
0.76	Intermediate Similarity	NPC211848
0.7372	Intermediate Similarity	NPC276822
0.7319	Intermediate Similarity	NPC243412
0.6818	Remote Similarity	NPC262880
0.6818	Remote Similarity	NPC247902
0.6763	Remote Similarity	NPC88943
0.6696	Remote Similarity	NPC168017
0.6579	Remote Similarity	NPC178632
0.6573	Remote Similarity	NPC956
0.6371	Remote Similarity	NPC241394
0.6304	Remote Similarity	NPC41162
0.629	Remote Similarity	NPC128303
0.6231	Remote Similarity	NPC272166
0.6207	Remote Similarity	NPC322966
0.6197	Remote Similarity	NPC82129
0.6195	Remote Similarity	NPC124359
0.6075	Remote Similarity	NPC29326
0.5984	Remote Similarity	NPC47076
0.5984	Remote Similarity	NPC134504
0.5942	Remote Similarity	NPC97580
0.5929	Remote Similarity	NPC212106
0.5926	Remote Similarity	NPC470788
0.5887	Remote Similarity	NPC220111
0.587	Remote Similarity	NPC473477
0.5862	Remote Similarity	NPC474210
0.5862	Remote Similarity	NPC277918
0.5852	Remote Similarity	NPC476155
0.5852	Remote Similarity	NPC17581
0.5821	Remote Similarity	NPC66007
0.5789	Remote Similarity	NPC470783
0.5766	Remote Similarity	NPC470593
0.5766	Remote Similarity	NPC470594
0.5753	Remote Similarity	NPC477400
0.5748	Remote Similarity	NPC194750
0.5748	Remote Similarity	NPC287638
0.5748	Remote Similarity	NPC233274
0.5732	Remote Similarity	NPC475342
0.5724	Remote Similarity	NPC313348
0.5724	Remote Similarity	NPC475987
0.5702	Remote Similarity	NPC476019
0.568	Remote Similarity	NPC292819
0.5667	Remote Similarity	NPC477399
0.5667	Remote Similarity	NPC477401
0.5659	Remote Similarity	NPC323720
0.5634	Remote Similarity	NPC470537
0.5625	Remote Similarity	NPC470592
0.5612	Remote Similarity	NPC238323

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 NPC271115 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	122
0.1-0.2	1744
0.2-0.3	4882
0.3-0.4	2017
0.4-0.5	315
0.5-0.6	58
0.6-0.7	12
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
0.6573	Remote Similarity	NPD5193	Discontinued
0.6522	Remote Similarity	NPD2682	Approved
0.6471	Remote Similarity	NPD3713	Approved
0.6471	Remote Similarity	NPD3715	Approved
0.6471	Remote Similarity	NPD3714	Approved
0.6281	Remote Similarity	NPD3104	Approved
0.6281	Remote Similarity	NPD3102	Approved
0.6281	Remote Similarity	NPD3103	Approved
0.6281	Remote Similarity	NPD3101	Approved
0.6231	Remote Similarity	NPD1000	Clinical (unspecified phase)
0.595	Remote Similarity	NPD2636	Clinical (unspecified phase)
0.595	Remote Similarity	NPD2637	Approved
0.5948	Remote Similarity	NPD3723	Clinical (unspecified phase)
0.5736	Remote Similarity	NPD6920	Discontinued
0.5672	Remote Similarity	NPD8298	Phase 2
0.5645	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