NPASS Compound

Structure

CID221111 OpenBabel06191716012D 23 26 0 0 1 0 0 0 0 0999 V2000 0.3090 -2.5691 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.2812 0.1910 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.7812 -0.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6831 0.6910 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5491 -1.8090 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4152 -1.3090 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4152 1.6910 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5491 1.1910 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 -1.8171 0.1910 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 -2.6831 -1.3090 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9511 -1.3090 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6831 -0.3090 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.9511 -0.3090 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.4152 -0.3090 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -5.2812 1.1910 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 0.5878 -0.8090 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2812 0.1910 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5491 0.1910 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -6.1472 1.6910 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.5878 -0.8090 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.0000 -0.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 11 1 0 0 0 0 2 19 1 0 0 0 0 3 19 1 0 0 0 0 5 6 1 0 0 0 0 5 12 1 0 0 0 0 6 16 1 0 0 0 0 7 8 1 0 0 0 0 7 17 1 0 0 0 0 8 20 1 0 0 0 0 9 12 2 0 0 0 0 9 13 1 0 0 0 0 10 14 1 0 0 0 0 11 13 2 0 0 0 0 11 18 1 0 0 0 0 12 14 1 0 0 0 0 13 15 1 0 0 0 0 14 20 1 6 0 0 0 15 10 1 1 0 0 0 15 23 1 0 0 0 0 16 19 1 0 0 0 0 16 20 1 6 0 0 0 17 19 1 0 0 0 0 17 21 1 6 0 0 0 18 22 2 0 0 0 0 18 23 1 0 0 0 0 20 4 1 6 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	316.2
Volume:	338.712
LogP:	4.178
LogD:	3.747
LogS:	-3.753
# Rotatable Bonds:	0
TPSA:	53.6
# H-Bond Aceptor:	3
# H-Bond Donor:	2
# Rings:	4
# Heavy Atoms:	3

MedChem Properties

QED Drug-Likeness Score:	0.743
Synthetic Accessibility Score:	4.574
Fsp3:	0.7
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected
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:	-4.772
MDCK Permeability:	2.3443801183020696e-05
Pgp-inhibitor:	0.178
Pgp-substrate:	0.587
Human Intestinal Absorption (HIA):	0.005
20% Bioavailability (F20%):	0.004
30% Bioavailability (F30%):	0.015

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.119
Plasma Protein Binding (PPB):	97.19204711914062%
Volume Distribution (VD):	2.048
Pgp-substrate:	3.373703718185425%

ADMET: Metabolism

CYP1A2-inhibitor:	0.159
CYP1A2-substrate:	0.34
CYP2C19-inhibitor:	0.036
CYP2C19-substrate:	0.744
CYP2C9-inhibitor:	0.295
CYP2C9-substrate:	0.578
CYP2D6-inhibitor:	0.017
CYP2D6-substrate:	0.643
CYP3A4-inhibitor:	0.074
CYP3A4-substrate:	0.245

ADMET: Excretion

Clearance (CL):	13.813
Half-life (T1/2):	0.153

ADMET: Toxicity

hERG Blockers:	0.019
Human Hepatotoxicity (H-HT):	0.682
Drug-inuced Liver Injury (DILI):	0.102
AMES Toxicity:	0.037
Rat Oral Acute Toxicity:	0.961
Maximum Recommended Daily Dose:	0.956
Skin Sensitization:	0.674
Carcinogencity:	0.537
Eye Corrosion:	0.008
Eye Irritation:	0.171
Respiratory Toxicity:	0.977

Download Data

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

Natural Product: NPC221111

Natural Product ID:	NPC221111
*Common Name:**	Helioscopinolide A
IUPAC Name:	(3R,4aS,10aR,11aR,11bS)-3-hydroxy-4,4,8,11b-tetramethyl-2,3,4a,5,6,10a,11,11a-octahydro-1H-naphtho[2,1-f][1]benzofuran-9-one
Synonyms:
Standard InCHIKey:	KZIADLALQLRZIQ-RXFYRGCNSA-N
Standard InCHI:	InChI=1S/C20H28O3/c1-11-13-9-12-5-6-16-19(2,3)17(21)7-8-20(16,4)14(12)10-15(13)23-18(11)22/h9,14-17,21H,5-8,10H2,1-4H3/t14-,15-,16-,17-,20+/m1/s1
SMILES:	O=C1O[C@H]2C(=C1C)C=C1[C@@H](C2)[C@]2(C)CC[C@H](C([C@H]2CC1)(C)C)O
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL469645
PubChem CID:	10245246
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001283] Terpene lactones [CHEMONTID:0001538] Diterpene lactones

*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
NPO28245	Strychnos nux-vomica	Species	Loganiaceae	Eukaryota	n.a.	seed	n.a.	PMID[10.1016/j.tet.2012.03.006]
NPO28245	Strychnos nux-vomica	Species	Loganiaceae	Eukaryota	n.a.	seed	n.a.	DOI[10.1016/j.tet.2012.03.006]
NPO11807	Euphorbia pubescens	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[15165162]
NPO28245	Strychnos nux-vomica	Species	Loganiaceae	Eukaryota	n.a.	seed	n.a.	PMID[16317898]
NPO16205	Euphorbia fischeriana	Species	Euphorbiaceae	Eukaryota	roots	n.a.	n.a.	PMID[16792421]
NPO28245	Strychnos nux-vomica	Species	Loganiaceae	Eukaryota	n.a.	seed	n.a.	PMID[17449162]
NPO12682	Euphorbia helioscopia	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[18321057]
NPO12682	Euphorbia helioscopia	Species	Euphorbiaceae	Eukaryota	n.a.	whole plant	n.a.	PMID[19099222]
NPO28245	Strychnos nux-vomica	Species	Loganiaceae	Eukaryota	n.a.	seed	n.a.	PMID[19235686]
NPO28245	Strychnos nux-vomica	Species	Loganiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[19666019]
NPO25837	Euphorbia micractina	Species	Euphorbiaceae	Eukaryota	Roots	Zhang County, Gansu Province, China	2002-Sep	PMID[19702283]
NPO16205	Euphorbia fischeriana	Species	Euphorbiaceae	Eukaryota	n.a.	whole plant	n.a.	PMID[21534540]
NPO16205	Euphorbia fischeriana	Species	Euphorbiaceae	Eukaryota	whole plants	Panshi, Jilin Province, China	2009-JUN	PMID[21534540]
NPO25837	Euphorbia micractina	Species	Euphorbiaceae	Eukaryota	n.a.	root	n.a.	PMID[21534583]
NPO28245	Strychnos nux-vomica	Species	Loganiaceae	Eukaryota	n.a.	seed	n.a.	PMID[22707864]
NPO28245	Strychnos nux-vomica	Species	Loganiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[23088673]
NPO25837	Euphorbia micractina	Species	Euphorbiaceae	Eukaryota	Roots	n.a.	n.a.	PMID[23691978]
NPO28245	Strychnos nux-vomica	Species	Loganiaceae	Eukaryota	n.a.	seed	n.a.	PMID[2393954]
NPO299	Euphorbia ebracteolata	Species	Euphorbiaceae	Eukaryota	roots	n.a.	n.a.	PMID[24660966]
NPO16205	Euphorbia fischeriana	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[25453801]
NPO28245	Strychnos nux-vomica	Species	Loganiaceae	Eukaryota	n.a.	seed	n.a.	PMID[25594733]
NPO16205	Euphorbia fischeriana	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[26702644]
NPO16205	Euphorbia fischeriana	Species	Euphorbiaceae	Eukaryota	Roots	n.a.	n.a.	PMID[28383891]
NPO299	Euphorbia ebracteolata	Species	Euphorbiaceae	Eukaryota	Roots	n.a.	n.a.	PMID[29148766]
NPO12682	Euphorbia helioscopia	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[30724086]
NPO299	Euphorbia ebracteolata	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[31184480]
NPO12682	Euphorbia helioscopia	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[31550154]
NPO28245	Strychnos nux-vomica	Species	Loganiaceae	Eukaryota	n.a.	seed	n.a.	PMID[7912074]
NPO17794	Streptomyces violaceusniger	Species	Streptomycetaceae	Bacteria	n.a.	n.a.	n.a.	PMID[8557611]
NPO28245	Strychnos nux-vomica	Species	Loganiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO16205	Euphorbia fischeriana	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO11807	Euphorbia pubescens	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO8770	Euphorbia wallichii	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO12682	Euphorbia helioscopia	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO8770	Euphorbia wallichii	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO299	Euphorbia ebracteolata	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO16205	Euphorbia fischeriana	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO11807	Euphorbia pubescens	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO12682	Euphorbia helioscopia	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO28245	Strychnos nux-vomica	Species	Loganiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO12190	Carduus acanthoides	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO299	Euphorbia ebracteolata	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO12682	Euphorbia helioscopia	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO28245	Strychnos nux-vomica	Species	Loganiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO299	Euphorbia ebracteolata	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO16205	Euphorbia fischeriana	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO28142	Anthoceros agrestis	Species	Anthocerotaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO21065	Euphorbia calyptrata	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO8770	Euphorbia wallichii	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO16205	Euphorbia fischeriana	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO1891	Chorilaena quercifolia	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO8081	Crataegus flava	Species	Rosaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO28332	Lecidea tumida	Species	Lecideaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO28157	Vriesea regina	Species	Bromeliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO28299	Leucaena diversifolia	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO28245	Strychnos nux-vomica	Species	Loganiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO12190	Carduus acanthoides	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO299	Euphorbia ebracteolata	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO27863	Diospyros nigra	Species	Ebenaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO5402	Hypogymnia billardieri	Species	Parmeliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO27972	Clitocybe phosphorea	Species	Tricholomataceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO16779.1	Amaranthus hybridus subsp. cruentus	Subspecies	Amaranthaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO12682	Euphorbia helioscopia	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO28007	Cakile maritima	Species	Brassicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO17794	Streptomyces violaceusniger	Species	Streptomycetaceae	Bacteria	n.a.	n.a.	n.a.	Database[UNPD]
NPO25837	Euphorbia micractina	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO6223	Ceiba insignis	Species	Malvaceae	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
GI50	3
IC50	2

Activity Type	# Activity
Cell Line	5

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT165	Cell Line	HeLa	Homo sapiens	IC50	=	110.0	nM	PMID[454403]
NPT82	Cell Line	MDA-MB-231	Homo sapiens	IC50	=	2100.0	nM	PMID[454403]
NPT83	Cell Line	MCF7	Homo sapiens	GI50	=	67500.0	nM	PMID[454404]
NPT397	Cell Line	NCI-H460	Homo sapiens	GI50	=	72780.0	nM	PMID[454404]
NPT395	Cell Line	SF-268	Homo sapiens	GI50	>	100000.0	nM	PMID[454404]

☑ 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 NPC221111 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	179
0.1-0.2	967
0.2-0.3	3717
0.3-0.4	8080
0.4-0.5	14621
0.5-0.6	7295
0.6-0.7	5423
0.7-0.8	2152
0.8-0.85	203
0.85-0.9	40
0.9-0.95	15
0.95-1	5

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC280149
0.9535	High Similarity	NPC310479
0.9318	High Similarity	NPC205034
0.9318	High Similarity	NPC152778
0.9318	High Similarity	NPC162615
0.931	High Similarity	NPC182136
0.907	High Similarity	NPC131813
0.9011	High Similarity	NPC16967
0.9011	High Similarity	NPC473153
0.9	High Similarity	NPC191521
0.8876	High Similarity	NPC78973
0.8817	High Similarity	NPC474440
0.8791	High Similarity	NPC470255
0.8778	High Similarity	NPC472811
0.8778	High Similarity	NPC72845
0.8764	High Similarity	NPC50488
0.8764	High Similarity	NPC474396
0.875	High Similarity	NPC473891
0.8721	High Similarity	NPC311070
0.8681	High Similarity	NPC53555
0.8681	High Similarity	NPC139692
0.8681	High Similarity	NPC472812
0.8636	High Similarity	NPC329692
0.8621	High Similarity	NPC96055
0.8617	High Similarity	NPC92275
0.8602	High Similarity	NPC190713
0.8588	High Similarity	NPC268827
0.8587	High Similarity	NPC57117
0.8571	High Similarity	NPC329842
0.8526	High Similarity	NPC474012
0.8526	High Similarity	NPC476299
0.8523	High Similarity	NPC474013
0.8511	High Similarity	NPC141401
0.8495	Intermediate Similarity	NPC276110
0.8488	Intermediate Similarity	NPC159148
0.8488	Intermediate Similarity	NPC142163
0.8469	Intermediate Similarity	NPC81630
0.8454	Intermediate Similarity	NPC45897
0.8452	Intermediate Similarity	NPC189206
0.8427	Intermediate Similarity	NPC471219
0.8421	Intermediate Similarity	NPC278673
0.8409	Intermediate Similarity	NPC32223
0.8404	Intermediate Similarity	NPC134072
0.8404	Intermediate Similarity	NPC472363
0.8404	Intermediate Similarity	NPC242848
0.8404	Intermediate Similarity	NPC234993
0.8404	Intermediate Similarity	NPC165632
0.8404	Intermediate Similarity	NPC260796
0.8404	Intermediate Similarity	NPC472362
0.8404	Intermediate Similarity	NPC154526
0.8391	Intermediate Similarity	NPC471218
0.8387	Intermediate Similarity	NPC105490
0.8372	Intermediate Similarity	NPC281880
0.837	Intermediate Similarity	NPC212948
0.8353	Intermediate Similarity	NPC184737
0.8352	Intermediate Similarity	NPC262858
0.8352	Intermediate Similarity	NPC146554
0.8352	Intermediate Similarity	NPC472240
0.8352	Intermediate Similarity	NPC473647
0.8351	Intermediate Similarity	NPC31058
0.8351	Intermediate Similarity	NPC114540
0.8351	Intermediate Similarity	NPC469606
0.8351	Intermediate Similarity	NPC273005
0.8351	Intermediate Similarity	NPC32577
0.8351	Intermediate Similarity	NPC155332
0.8333	Intermediate Similarity	NPC117685
0.8333	Intermediate Similarity	NPC201406
0.8333	Intermediate Similarity	NPC312561
0.8316	Intermediate Similarity	NPC51499
0.8316	Intermediate Similarity	NPC132753
0.8316	Intermediate Similarity	NPC253826
0.8316	Intermediate Similarity	NPC224356
0.8316	Intermediate Similarity	NPC99726
0.8316	Intermediate Similarity	NPC121402
0.8316	Intermediate Similarity	NPC151681
0.8316	Intermediate Similarity	NPC73911
0.8316	Intermediate Similarity	NPC175351
0.8315	Intermediate Similarity	NPC471795
0.8315	Intermediate Similarity	NPC109528
0.8315	Intermediate Similarity	NPC86316
0.8315	Intermediate Similarity	NPC106416
0.8298	Intermediate Similarity	NPC183012
0.8298	Intermediate Similarity	NPC209355
0.8298	Intermediate Similarity	NPC472441
0.8295	Intermediate Similarity	NPC472377
0.8295	Intermediate Similarity	NPC42476
0.8295	Intermediate Similarity	NPC474789
0.8295	Intermediate Similarity	NPC52108
0.8295	Intermediate Similarity	NPC57370
0.8283	Intermediate Similarity	NPC469607
0.828	Intermediate Similarity	NPC214697
0.828	Intermediate Similarity	NPC7349
0.828	Intermediate Similarity	NPC38232
0.8276	Intermediate Similarity	NPC170303
0.8265	Intermediate Similarity	NPC23584
0.8256	Intermediate Similarity	NPC100906
0.8247	Intermediate Similarity	NPC303559
0.8242	Intermediate Similarity	NPC24816
0.8242	Intermediate Similarity	NPC472809
0.8242	Intermediate Similarity	NPC472810
0.8235	Intermediate Similarity	NPC283619
0.8229	Intermediate Similarity	NPC278386
0.8229	Intermediate Similarity	NPC218107
0.8229	Intermediate Similarity	NPC124512
0.8229	Intermediate Similarity	NPC159763
0.8229	Intermediate Similarity	NPC325229
0.8229	Intermediate Similarity	NPC108368
0.8229	Intermediate Similarity	NPC473154
0.8229	Intermediate Similarity	NPC275086
0.8229	Intermediate Similarity	NPC57079
0.8222	Intermediate Similarity	NPC474970
0.8202	Intermediate Similarity	NPC302360
0.8191	Intermediate Similarity	NPC201725
0.8191	Intermediate Similarity	NPC119562
0.8191	Intermediate Similarity	NPC104925
0.8191	Intermediate Similarity	NPC298973
0.8191	Intermediate Similarity	NPC469697
0.8191	Intermediate Similarity	NPC279410
0.8182	Intermediate Similarity	NPC256112
0.8172	Intermediate Similarity	NPC477574
0.8172	Intermediate Similarity	NPC233345
0.8172	Intermediate Similarity	NPC234335
0.8172	Intermediate Similarity	NPC186363
0.8172	Intermediate Similarity	NPC472814
0.8172	Intermediate Similarity	NPC177037
0.8163	Intermediate Similarity	NPC273668
0.8163	Intermediate Similarity	NPC11956
0.8163	Intermediate Similarity	NPC476081
0.8161	Intermediate Similarity	NPC10636
0.8152	Intermediate Similarity	NPC470734
0.8152	Intermediate Similarity	NPC5509
0.8152	Intermediate Similarity	NPC16265
0.8144	Intermediate Similarity	NPC251680
0.8144	Intermediate Similarity	NPC474190
0.8144	Intermediate Similarity	NPC266955
0.8144	Intermediate Similarity	NPC38855
0.8132	Intermediate Similarity	NPC166857
0.8125	Intermediate Similarity	NPC208094
0.8125	Intermediate Similarity	NPC474343
0.8125	Intermediate Similarity	NPC231751
0.8111	Intermediate Similarity	NPC30984
0.8111	Intermediate Similarity	NPC65661
0.8111	Intermediate Similarity	NPC473251
0.8111	Intermediate Similarity	NPC476602
0.8111	Intermediate Similarity	NPC42586
0.8111	Intermediate Similarity	NPC35933
0.8105	Intermediate Similarity	NPC474909
0.8105	Intermediate Similarity	NPC295347
0.81	Intermediate Similarity	NPC478052
0.81	Intermediate Similarity	NPC471206
0.81	Intermediate Similarity	NPC478208
0.81	Intermediate Similarity	NPC34768
0.81	Intermediate Similarity	NPC266570
0.809	Intermediate Similarity	NPC79945
0.809	Intermediate Similarity	NPC474193
0.809	Intermediate Similarity	NPC12283
0.809	Intermediate Similarity	NPC476927
0.8085	Intermediate Similarity	NPC115021
0.8085	Intermediate Similarity	NPC472303
0.8085	Intermediate Similarity	NPC472640
0.8085	Intermediate Similarity	NPC472641
0.8081	Intermediate Similarity	NPC297617
0.8081	Intermediate Similarity	NPC120321
0.8081	Intermediate Similarity	NPC112009
0.8068	Intermediate Similarity	NPC475944
0.8065	Intermediate Similarity	NPC281942
0.8065	Intermediate Similarity	NPC51486
0.8065	Intermediate Similarity	NPC220454
0.8065	Intermediate Similarity	NPC472642
0.8065	Intermediate Similarity	NPC232426
0.8065	Intermediate Similarity	NPC8062
0.8065	Intermediate Similarity	NPC212679
0.8065	Intermediate Similarity	NPC38952
0.8065	Intermediate Similarity	NPC469595
0.8061	Intermediate Similarity	NPC471412
0.8061	Intermediate Similarity	NPC11974
0.8061	Intermediate Similarity	NPC115899
0.8061	Intermediate Similarity	NPC247701
0.8061	Intermediate Similarity	NPC473160
0.8061	Intermediate Similarity	NPC25177
0.8061	Intermediate Similarity	NPC268829
0.8061	Intermediate Similarity	NPC222875
0.8061	Intermediate Similarity	NPC295110
0.8046	Intermediate Similarity	NPC242767
0.8043	Intermediate Similarity	NPC93411
0.8043	Intermediate Similarity	NPC472378
0.8043	Intermediate Similarity	NPC473879
0.8043	Intermediate Similarity	NPC472302
0.8041	Intermediate Similarity	NPC478056
0.8041	Intermediate Similarity	NPC181147
0.8023	Intermediate Similarity	NPC54996
0.8022	Intermediate Similarity	NPC82979
0.8022	Intermediate Similarity	NPC325594
0.8021	Intermediate Similarity	NPC88009
0.8021	Intermediate Similarity	NPC162346
0.802	Intermediate Similarity	NPC110496
0.802	Intermediate Similarity	NPC179380
0.8	Intermediate Similarity	NPC38830
0.8	Intermediate Similarity	NPC476186
0.8	Intermediate Similarity	NPC477129

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 NPC221111 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	155
0.1-0.2	1133
0.2-0.3	3481
0.3-0.4	2729
0.4-0.5	1150
0.5-0.6	237
0.6-0.7	213
0.7-0.8	51
0.8-0.85	1
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.8229	Intermediate Similarity	NPD7638	Approved
0.8229	Intermediate Similarity	NPD4225	Approved
0.8144	Intermediate Similarity	NPD7640	Approved
0.8144	Intermediate Similarity	NPD7639	Approved
0.7778	Intermediate Similarity	NPD4752	Clinical (unspecified phase)
0.7634	Intermediate Similarity	NPD3618	Phase 1
0.7629	Intermediate Similarity	NPD7748	Approved
0.7604	Intermediate Similarity	NPD7515	Phase 2
0.7451	Intermediate Similarity	NPD7632	Discontinued
0.7419	Intermediate Similarity	NPD6400	Clinical (unspecified phase)
0.74	Intermediate Similarity	NPD7902	Approved
0.7396	Intermediate Similarity	NPD5328	Approved
0.7391	Intermediate Similarity	NPD3667	Approved
0.7364	Intermediate Similarity	NPD7115	Discovery
0.7358	Intermediate Similarity	NPD4061	Clinical (unspecified phase)
0.7347	Intermediate Similarity	NPD6399	Phase 3
0.734	Intermediate Similarity	NPD1694	Approved
0.7303	Intermediate Similarity	NPD3701	Clinical (unspecified phase)
0.7264	Intermediate Similarity	NPD6686	Approved
0.7263	Intermediate Similarity	NPD6409	Approved
0.7263	Intermediate Similarity	NPD5330	Approved
0.7263	Intermediate Similarity	NPD6684	Approved
0.7263	Intermediate Similarity	NPD5279	Phase 3
0.7263	Intermediate Similarity	NPD7334	Approved
0.7263	Intermediate Similarity	NPD7521	Approved
0.7263	Intermediate Similarity	NPD7146	Approved
0.7253	Intermediate Similarity	NPD7645	Phase 2
0.7245	Intermediate Similarity	NPD6411	Approved
0.7245	Intermediate Similarity	NPD6079	Approved
0.7245	Intermediate Similarity	NPD7637	Suspended
0.7238	Intermediate Similarity	NPD7128	Approved
0.7238	Intermediate Similarity	NPD6402	Approved
0.7238	Intermediate Similarity	NPD6675	Approved
0.7238	Intermediate Similarity	NPD5739	Approved
0.7234	Intermediate Similarity	NPD3666	Approved
0.7234	Intermediate Similarity	NPD4786	Approved
0.7234	Intermediate Similarity	NPD3665	Phase 1
0.7234	Intermediate Similarity	NPD3133	Approved
0.7216	Intermediate Similarity	NPD6051	Approved
0.7191	Intermediate Similarity	NPD6942	Approved
0.7191	Intermediate Similarity	NPD8264	Approved
0.7191	Intermediate Similarity	NPD7339	Approved
0.7172	Intermediate Similarity	NPD4202	Approved
0.717	Intermediate Similarity	NPD5697	Approved
0.717	Intermediate Similarity	NPD5701	Approved
0.713	Intermediate Similarity	NPD5955	Clinical (unspecified phase)
0.7113	Intermediate Similarity	NPD6903	Approved
0.7113	Intermediate Similarity	NPD7513	Clinical (unspecified phase)
0.7103	Intermediate Similarity	NPD6881	Approved
0.7103	Intermediate Similarity	NPD6011	Approved
0.7103	Intermediate Similarity	NPD7320	Approved
0.7103	Intermediate Similarity	NPD6899	Approved
0.71	Intermediate Similarity	NPD7901	Clinical (unspecified phase)
0.71	Intermediate Similarity	NPD7900	Approved
0.7079	Intermediate Similarity	NPD6926	Approved
0.7079	Intermediate Similarity	NPD6924	Approved
0.7059	Intermediate Similarity	NPD6084	Phase 2
0.7059	Intermediate Similarity	NPD6083	Phase 2
0.7041	Intermediate Similarity	NPD5764	Clinical (unspecified phase)
0.7041	Intermediate Similarity	NPD6101	Approved
0.7037	Intermediate Similarity	NPD6372	Approved
0.7037	Intermediate Similarity	NPD6013	Approved
0.7037	Intermediate Similarity	NPD6012	Approved
0.7037	Intermediate Similarity	NPD6014	Approved
0.7037	Intermediate Similarity	NPD6373	Approved
0.701	Intermediate Similarity	NPD3573	Approved
0.7	Intermediate Similarity	NPD5779	Approved
0.7	Intermediate Similarity	NPD5778	Approved
0.6991	Remote Similarity	NPD7327	Approved
0.6991	Remote Similarity	NPD7328	Approved
0.6989	Remote Similarity	NPD7525	Registered
0.6979	Remote Similarity	NPD7520	Clinical (unspecified phase)
0.6972	Remote Similarity	NPD6883	Approved
0.6972	Remote Similarity	NPD7102	Approved
0.6972	Remote Similarity	NPD7290	Approved
0.6961	Remote Similarity	NPD5220	Clinical (unspecified phase)
0.6961	Remote Similarity	NPD5222	Approved
0.6961	Remote Similarity	NPD5221	Approved
0.6961	Remote Similarity	NPD4697	Phase 3
0.6957	Remote Similarity	NPD8033	Approved
0.6957	Remote Similarity	NPD7503	Approved
0.6947	Remote Similarity	NPD6695	Phase 3
0.6939	Remote Similarity	NPD6672	Approved
0.6939	Remote Similarity	NPD5737	Approved
0.693	Remote Similarity	NPD7516	Approved
0.6923	Remote Similarity	NPD6933	Approved
0.6923	Remote Similarity	NPD6648	Approved
0.6909	Remote Similarity	NPD6649	Approved
0.6909	Remote Similarity	NPD8130	Phase 1
0.6909	Remote Similarity	NPD6650	Approved
0.6909	Remote Similarity	NPD6617	Approved
0.6909	Remote Similarity	NPD6847	Approved
0.6909	Remote Similarity	NPD6401	Clinical (unspecified phase)
0.6909	Remote Similarity	NPD6869	Approved
0.69	Remote Similarity	NPD5693	Phase 1
0.6893	Remote Similarity	NPD5173	Approved
0.6893	Remote Similarity	NPD4755	Approved
0.6882	Remote Similarity	NPD6929	Approved
0.6875	Remote Similarity	NPD7338	Clinical (unspecified phase)
0.687	Remote Similarity	NPD8377	Approved
0.687	Remote Similarity	NPD8294	Approved
0.6869	Remote Similarity	NPD7285	Clinical (unspecified phase)
0.6863	Remote Similarity	NPD5695	Phase 3
0.6857	Remote Similarity	NPD5344	Discontinued
0.6854	Remote Similarity	NPD7151	Approved
0.6854	Remote Similarity	NPD7152	Approved
0.6854	Remote Similarity	NPD7150	Approved
0.6852	Remote Similarity	NPD5954	Clinical (unspecified phase)
0.6847	Remote Similarity	NPD8297	Approved
0.6847	Remote Similarity	NPD6882	Approved
0.6837	Remote Similarity	NPD4751	Clinical (unspecified phase)
0.6827	Remote Similarity	NPD5696	Approved
0.6818	Remote Similarity	NPD6923	Approved
0.6818	Remote Similarity	NPD6922	Approved
0.6813	Remote Similarity	NPD8039	Approved
0.681	Remote Similarity	NPD8379	Approved
0.681	Remote Similarity	NPD8296	Approved
0.681	Remote Similarity	NPD8378	Approved
0.681	Remote Similarity	NPD8380	Approved
0.681	Remote Similarity	NPD8335	Approved
0.6809	Remote Similarity	NPD4695	Discontinued
0.6809	Remote Similarity	NPD6930	Phase 2
0.6809	Remote Similarity	NPD6931	Approved
0.6809	Remote Similarity	NPD7509	Discontinued
0.6804	Remote Similarity	NPD1696	Phase 3
0.68	Remote Similarity	NPD7838	Discovery
0.6792	Remote Similarity	NPD5211	Phase 2
0.6774	Remote Similarity	NPD7322	Clinical (unspecified phase)
0.6762	Remote Similarity	NPD4700	Approved
0.6762	Remote Similarity	NPD5286	Approved
0.6762	Remote Similarity	NPD5285	Approved
0.6762	Remote Similarity	NPD4696	Approved
0.6759	Remote Similarity	NPD6008	Approved
0.6742	Remote Similarity	NPD7144	Approved
0.6742	Remote Similarity	NPD7143	Approved
0.6735	Remote Similarity	NPD4623	Approved
0.6735	Remote Similarity	NPD4519	Discontinued
0.6733	Remote Similarity	NPD8034	Phase 2
0.6733	Remote Similarity	NPD8035	Phase 2
0.6733	Remote Similarity	NPD5281	Approved
0.6733	Remote Similarity	NPD5284	Approved
0.6723	Remote Similarity	NPD7507	Approved
0.6702	Remote Similarity	NPD4195	Approved
0.6701	Remote Similarity	NPD3668	Phase 3
0.67	Remote Similarity	NPD4753	Phase 2
0.6699	Remote Similarity	NPD6356	Clinical (unspecified phase)
0.6698	Remote Similarity	NPD5223	Approved
0.6667	Remote Similarity	NPD6925	Approved
0.6667	Remote Similarity	NPD5776	Phase 2
0.6667	Remote Similarity	NPD4221	Approved
0.6667	Remote Similarity	NPD6868	Approved
0.6667	Remote Similarity	NPD7524	Approved
0.6667	Remote Similarity	NPD4223	Phase 3
0.6667	Remote Similarity	NPD5209	Approved
0.6667	Remote Similarity	NPD5290	Discontinued
0.6667	Remote Similarity	NPD5141	Approved
0.6667	Remote Similarity	NPD6274	Approved
0.6667	Remote Similarity	NPD7750	Discontinued
0.6637	Remote Similarity	NPD4632	Approved
0.6636	Remote Similarity	NPD4633	Approved
0.6636	Remote Similarity	NPD5224	Approved
0.6636	Remote Similarity	NPD5226	Approved
0.6636	Remote Similarity	NPD5225	Approved
0.6634	Remote Similarity	NPD5785	Approved
0.6634	Remote Similarity	NPD5207	Approved
0.6634	Remote Similarity	NPD5692	Phase 3
0.6632	Remote Similarity	NPD8259	Clinical (unspecified phase)
0.6632	Remote Similarity	NPD7514	Phase 3
0.6632	Remote Similarity	NPD7332	Phase 2
0.6628	Remote Similarity	NPD5325	Clinical (unspecified phase)
0.6609	Remote Similarity	NPD6317	Approved
0.6602	Remote Similarity	NPD6001	Approved
0.66	Remote Similarity	NPD5208	Approved
0.6596	Remote Similarity	NPD7145	Approved
0.6574	Remote Similarity	NPD5174	Approved
0.6574	Remote Similarity	NPD5175	Approved
0.6574	Remote Similarity	NPD4754	Approved
0.6569	Remote Similarity	NPD5694	Approved
0.6569	Remote Similarity	NPD6050	Approved
0.6566	Remote Similarity	NPD3574	Clinical (unspecified phase)
0.6566	Remote Similarity	NPD5280	Approved
0.6566	Remote Similarity	NPD4694	Approved
0.6562	Remote Similarity	NPD6902	Approved
0.6557	Remote Similarity	NPD7319	Approved
0.6552	Remote Similarity	NPD6335	Approved
0.6552	Remote Similarity	NPD6313	Approved
0.6552	Remote Similarity	NPD2685	Clinical (unspecified phase)
0.6552	Remote Similarity	NPD6314	Approved
0.6549	Remote Similarity	NPD6053	Discontinued
0.6542	Remote Similarity	NPD4159	Approved
0.6538	Remote Similarity	NPD1698	Clinical (unspecified phase)
0.6535	Remote Similarity	NPD6904	Approved
0.6535	Remote Similarity	NPD6673	Approved
0.6535	Remote Similarity	NPD6080	Approved
0.6531	Remote Similarity	NPD4197	Approved
0.6509	Remote Similarity	NPD8029	Clinical (unspecified phase)
0.6496	Remote Similarity	NPD7100	Approved
0.6496	Remote Similarity	NPD7101	Approved
0.6489	Remote Similarity	NPD6932	Approved
0.6471	Remote Similarity	NPD6698	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