NPASS Compound

Structure

NPC473900 OpenBabel07101718322D 28 33 0 0 0 0 0 0 0 0999 V2000 -3.1277 -1.5827 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0685 -1.5827 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9345 -3.0827 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3956 -2.5827 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5296 -4.0827 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2024 -4.0827 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9945 -0.1045 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2709 -5.6654 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5981 -5.6654 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0685 -2.5827 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5296 -3.0827 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2024 -1.0827 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2024 -3.0827 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9345 -4.0827 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0685 -4.5827 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2617 -3.0827 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3956 -4.5827 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3364 -2.5827 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3364 -1.5827 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2617 -4.0827 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4067 -0.9135 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3849 -1.1215 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.1277 -2.5827 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 3.6776 -4.7518 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.2764 -5.5608 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.6036 -5.5608 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.0048 -4.7518 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 23 1 0 0 0 0 2 10 2 0 0 0 0 2 12 1 0 0 0 0 3 10 1 0 0 0 0 3 14 2 0 0 0 0 4 11 2 0 0 0 0 4 16 1 0 0 0 0 5 11 1 0 0 0 0 5 17 2 0 0 0 0 6 13 1 0 0 0 0 6 15 2 0 0 0 0 7 12 1 0 0 0 0 7 24 1 0 0 0 0 8 25 1 0 0 0 0 8 26 1 0 0 0 0 9 27 1 0 0 0 0 9 28 1 0 0 0 0 10 13 1 0 0 0 0 11 18 1 0 0 0 0 12 19 2 0 0 0 0 13 18 2 0 0 0 0 14 15 1 0 0 0 0 14 25 1 0 0 0 0 15 26 1 0 0 0 0 16 20 2 0 0 0 0 16 23 1 0 0 0 0 17 20 1 0 0 0 0 17 27 1 0 0 0 0 18 19 1 0 0 0 0 19 21 1 0 0 0 0 20 28 1 0 0 0 0 21 22 2 0 0 0 0 21 24 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	378.07
Volume:	358.237
LogP:	4.119
LogD:	3.195
LogS:	-6.948
# Rotatable Bonds:	2
TPSA:	72.45
# H-Bond Aceptor:	7
# H-Bond Donor:	0
# Rings:	6
# Heavy Atoms:	7

MedChem Properties

QED Drug-Likeness Score:	0.631
Synthetic Accessibility Score:	2.794
Fsp3:	0.19
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:	-5.2
MDCK Permeability:	6.976720032980666e-05
Pgp-inhibitor:	0.078
Pgp-substrate:	0.001
Human Intestinal Absorption (HIA):	0.001
20% Bioavailability (F20%):	0.004
30% Bioavailability (F30%):	0.005

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.049
Plasma Protein Binding (PPB):	93.20337677001953%
Volume Distribution (VD):	0.857
Pgp-substrate:	1.1443294286727905%

ADMET: Metabolism

CYP1A2-inhibitor:	0.97
CYP1A2-substrate:	0.201
CYP2C19-inhibitor:	0.98
CYP2C19-substrate:	0.096
CYP2C9-inhibitor:	0.775
CYP2C9-substrate:	0.932
CYP2D6-inhibitor:	0.944
CYP2D6-substrate:	0.932
CYP3A4-inhibitor:	0.93
CYP3A4-substrate:	0.107

ADMET: Excretion

Clearance (CL):	14.178
Half-life (T1/2):	0.134

ADMET: Toxicity

hERG Blockers:	0.089
Human Hepatotoxicity (H-HT):	0.084
Drug-inuced Liver Injury (DILI):	0.902
AMES Toxicity:	0.782
Rat Oral Acute Toxicity:	0.021
Maximum Recommended Daily Dose:	0.914
Skin Sensitization:	0.344
Carcinogencity:	0.942
Eye Corrosion:	0.003
Eye Irritation:	0.152
Respiratory Toxicity:	0.624

Download Data

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

Natural Product: NPC473900

Natural Product ID:	NPC473900
*Common Name:**	5-(7-Methoxy-1,3-Benzodioxol-5-Yl)-8H-[2]Benzofuro[5,6-F][1,3]Benzodioxol-6-One
IUPAC Name:	5-(7-methoxy-1,3-benzodioxol-5-yl)-8H-[2]benzofuro[5,6-f][1,3]benzodioxol-6-one
Synonyms:	koelreuterin-1
Standard InCHIKey:	HTPDVTGSLPGCBF-UHFFFAOYSA-N
Standard InCHI:	InChI=1S/C21H14O7/c1-23-16-4-11(5-17-20(16)28-9-27-17)18-13-6-15-14(25-8-26-15)3-10(13)2-12-7-24-21(22)19(12)18/h2-6H,7-9H2,1H3
SMILES:	COc1cc(cc2c1OCO2)c1c2C(=O)OCc2cc2c1cc1OCOc1c2
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL454590
PubChem CID:	10317484
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0001392] Lignans, neolignans and related compounds [CHEMONTID:0001610] Arylnaphthalene lignans

*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
NPO4224	Koelreuteria henryi	Species	Sapindaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[7714533]
NPO4224	Koelreuteria henryi	Species	Sapindaceae	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
ED50	8
IC50	2

Activity Type	# Activity
Cell Line	8
Others	2

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT762	Cell Line	A-431	Homo sapiens	ED50	=	1.8	10'-1 ug/ml	PMID[548135]
NPT376	Cell Line	A498	Homo sapiens	ED50	=	7.8	10'-2 ug/ml	PMID[548135]
NPT81	Cell Line	A549	Homo sapiens	ED50	=	4.9	10'-2 ug/ml	PMID[548135]
NPT139	Cell Line	HT-29	Homo sapiens	ED50	=	2.9	10'-1 ug/ml	PMID[548135]
NPT83	Cell Line	MCF7	Homo sapiens	ED50	=	9.7	ug ml-1	PMID[548135]
NPT306	Cell Line	PC-3	Homo sapiens	ED50	=	1.5	10'-1 ug/ml	PMID[548135]
NPT373	Cell Line	SK-MEL-5	Homo sapiens	ED50	=	3.5	10'-3 ug/ml	PMID[548135]
NPT146	Cell Line	SK-OV-3	Homo sapiens	ED50	=	6.7	10'-3 ug/ml	PMID[548135]
NPT2	Others	Unspecified		IC50	=	5000.0	nM	PMID[548135]
NPT2	Others	Unspecified		IC50	=	20000.0	nM	PMID[548135]

☑ 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 NPC473900 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	430
0.1-0.2	1908
0.2-0.3	4061
0.3-0.4	10922
0.4-0.5	7711
0.5-0.6	3904
0.6-0.7	8204
0.7-0.8	5360
0.8-0.85	135
0.85-0.9	45
0.9-0.95	13
0.95-1	4

Similarity Score	Similarity Level	Natural Product ID
0.9799	High Similarity	NPC234730
0.9605	High Similarity	NPC474043
0.9539	High Similarity	NPC19600
0.9355	High Similarity	NPC15212
0.9346	High Similarity	NPC239113
0.9346	High Similarity	NPC115123
0.9342	High Similarity	NPC54179
0.9329	High Similarity	NPC181464
0.9267	High Similarity	NPC262455
0.9267	High Similarity	NPC177476
0.9267	High Similarity	NPC24193
0.9241	High Similarity	NPC174734
0.9241	High Similarity	NPC474042
0.9172	High Similarity	NPC198796
0.9167	High Similarity	NPC78944
0.9139	High Similarity	NPC127827
0.9133	High Similarity	NPC104024
0.9133	High Similarity	NPC65574
0.9133	High Similarity	NPC304687
0.9133	High Similarity	NPC80230
0.9133	High Similarity	NPC101755
0.9125	High Similarity	NPC117911
0.9103	High Similarity	NPC125713
0.9079	High Similarity	NPC475722
0.9051	High Similarity	NPC116838
0.9051	High Similarity	NPC22130
0.8987	High Similarity	NPC209411
0.8987	High Similarity	NPC239890
0.8954	High Similarity	NPC149505
0.8947	High Similarity	NPC40654
0.8947	High Similarity	NPC262804
0.8896	High Similarity	NPC210642
0.8896	High Similarity	NPC13985
0.8882	High Similarity	NPC471923
0.8868	High Similarity	NPC258322
0.8868	High Similarity	NPC191352
0.8848	High Similarity	NPC196771
0.8841	High Similarity	NPC184624
0.8839	High Similarity	NPC118332
0.8827	High Similarity	NPC473531
0.8827	High Similarity	NPC475453
0.8816	High Similarity	NPC193779
0.8808	High Similarity	NPC191158
0.8808	High Similarity	NPC177644
0.8808	High Similarity	NPC218841
0.8808	High Similarity	NPC92693
0.8726	High Similarity	NPC103197
0.8726	High Similarity	NPC273578
0.8726	High Similarity	NPC30009
0.8718	High Similarity	NPC104353
0.8688	High Similarity	NPC470637
0.8688	High Similarity	NPC96593
0.8684	High Similarity	NPC475000
0.8683	High Similarity	NPC35266
0.8675	High Similarity	NPC176586
0.8675	High Similarity	NPC210354
0.8675	High Similarity	NPC40237
0.8675	High Similarity	NPC151423
0.8667	High Similarity	NPC471921
0.8667	High Similarity	NPC114550
0.8667	High Similarity	NPC473697
0.8667	High Similarity	NPC312006
0.8667	High Similarity	NPC474075
0.8667	High Similarity	NPC471922
0.8667	High Similarity	NPC129930
0.8667	High Similarity	NPC20114
0.8667	High Similarity	NPC471920
0.8667	High Similarity	NPC292712
0.8634	High Similarity	NPC319749
0.8634	High Similarity	NPC288149
0.8616	High Similarity	NPC109765
0.8616	High Similarity	NPC237946
0.8616	High Similarity	NPC32373
0.8616	High Similarity	NPC301897
0.8609	High Similarity	NPC162851
0.8609	High Similarity	NPC246474
0.8609	High Similarity	NPC218092
0.8608	High Similarity	NPC348849
0.8608	High Similarity	NPC178195
0.8598	High Similarity	NPC79322
0.858	High Similarity	NPC280778
0.858	High Similarity	NPC61141
0.8571	High Similarity	NPC474770
0.8571	High Similarity	NPC65784
0.8562	High Similarity	NPC163527
0.8562	High Similarity	NPC202495
0.8562	High Similarity	NPC19947
0.8562	High Similarity	NPC143328
0.8562	High Similarity	NPC207584
0.8562	High Similarity	NPC181168
0.8562	High Similarity	NPC115281
0.8535	High Similarity	NPC303519
0.8509	High Similarity	NPC325122
0.848	Intermediate Similarity	NPC114120
0.848	Intermediate Similarity	NPC167045
0.8476	Intermediate Similarity	NPC477884
0.8457	Intermediate Similarity	NPC268718
0.8457	Intermediate Similarity	NPC119910
0.8457	Intermediate Similarity	NPC150943
0.8457	Intermediate Similarity	NPC91634
0.8428	Intermediate Similarity	NPC245948
0.8424	Intermediate Similarity	NPC83049
0.8424	Intermediate Similarity	NPC118162
0.8424	Intermediate Similarity	NPC320471
0.8418	Intermediate Similarity	NPC164082
0.8412	Intermediate Similarity	NPC161609
0.8412	Intermediate Similarity	NPC275690
0.8405	Intermediate Similarity	NPC100465
0.8405	Intermediate Similarity	NPC115624
0.8405	Intermediate Similarity	NPC152424
0.8387	Intermediate Similarity	NPC474158
0.8382	Intermediate Similarity	NPC286301
0.8382	Intermediate Similarity	NPC313063
0.8377	Intermediate Similarity	NPC474288
0.8373	Intermediate Similarity	NPC311912
0.8365	Intermediate Similarity	NPC220577
0.8354	Intermediate Similarity	NPC261322
0.8354	Intermediate Similarity	NPC300983
0.8343	Intermediate Similarity	NPC193377
0.8333	Intermediate Similarity	NPC87295
0.8323	Intermediate Similarity	NPC88557
0.8323	Intermediate Similarity	NPC254163
0.8303	Intermediate Similarity	NPC116759
0.8303	Intermediate Similarity	NPC14294
0.8302	Intermediate Similarity	NPC32079
0.8302	Intermediate Similarity	NPC477700
0.8291	Intermediate Similarity	NPC474965
0.8291	Intermediate Similarity	NPC85141
0.8291	Intermediate Similarity	NPC216223
0.8291	Intermediate Similarity	NPC293757
0.8291	Intermediate Similarity	NPC477695
0.8291	Intermediate Similarity	NPC668
0.8291	Intermediate Similarity	NPC174512
0.8291	Intermediate Similarity	NPC477698
0.8291	Intermediate Similarity	NPC145569
0.8284	Intermediate Similarity	NPC72455
0.8278	Intermediate Similarity	NPC72796
0.8278	Intermediate Similarity	NPC44245
0.8278	Intermediate Similarity	NPC211386
0.8272	Intermediate Similarity	NPC261484
0.8272	Intermediate Similarity	NPC477380
0.8263	Intermediate Similarity	NPC471180
0.8258	Intermediate Similarity	NPC137920
0.8258	Intermediate Similarity	NPC125134
0.8258	Intermediate Similarity	NPC86455
0.8253	Intermediate Similarity	NPC222531
0.8242	Intermediate Similarity	NPC19948
0.8242	Intermediate Similarity	NPC76687
0.8225	Intermediate Similarity	NPC178737
0.8224	Intermediate Similarity	NPC11453
0.8224	Intermediate Similarity	NPC230968
0.8224	Intermediate Similarity	NPC102260
0.8221	Intermediate Similarity	NPC82733
0.8221	Intermediate Similarity	NPC76458
0.8221	Intermediate Similarity	NPC477885
0.8214	Intermediate Similarity	NPC41853
0.8212	Intermediate Similarity	NPC110958
0.8212	Intermediate Similarity	NPC19890
0.821	Intermediate Similarity	NPC202249
0.821	Intermediate Similarity	NPC188962
0.821	Intermediate Similarity	NPC478238
0.821	Intermediate Similarity	NPC42871
0.8205	Intermediate Similarity	NPC18211
0.8204	Intermediate Similarity	NPC306475
0.8199	Intermediate Similarity	NPC144162
0.8199	Intermediate Similarity	NPC477377
0.8199	Intermediate Similarity	NPC308555
0.8193	Intermediate Similarity	NPC475865
0.8187	Intermediate Similarity	NPC474975
0.8176	Intermediate Similarity	NPC477881
0.8171	Intermediate Similarity	NPC15764
0.8171	Intermediate Similarity	NPC68619
0.816	Intermediate Similarity	NPC155063
0.8155	Intermediate Similarity	NPC167479
0.8155	Intermediate Similarity	NPC185498
0.8146	Intermediate Similarity	NPC205915
0.8137	Intermediate Similarity	NPC477378
0.8137	Intermediate Similarity	NPC474414
0.8137	Intermediate Similarity	NPC475229
0.8137	Intermediate Similarity	NPC477699
0.8137	Intermediate Similarity	NPC56184
0.8133	Intermediate Similarity	NPC108767
0.8129	Intermediate Similarity	NPC66804
0.8125	Intermediate Similarity	NPC316989
0.8121	Intermediate Similarity	NPC139876
0.8118	Intermediate Similarity	NPC475964
0.8118	Intermediate Similarity	NPC471181
0.8117	Intermediate Similarity	NPC470962
0.8113	Intermediate Similarity	NPC252281
0.8113	Intermediate Similarity	NPC477375
0.8113	Intermediate Similarity	NPC198129
0.8113	Intermediate Similarity	NPC327352
0.811	Intermediate Similarity	NPC310206
0.8101	Intermediate Similarity	NPC321696
0.8101	Intermediate Similarity	NPC321958
0.8101	Intermediate Similarity	NPC224687
0.8101	Intermediate Similarity	NPC3982
0.8092	Intermediate Similarity	NPC31530
0.8089	Intermediate Similarity	NPC143092
0.8089	Intermediate Similarity	NPC166884

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 NPC473900 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	379
0.1-0.2	994
0.2-0.3	1673
0.3-0.4	2842
0.4-0.5	1881
0.5-0.6	922
0.6-0.7	371
0.7-0.8	79
0.8-0.85	9
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.8616	High Similarity	NPD4967	Phase 2
0.8616	High Similarity	NPD4966	Approved
0.8616	High Similarity	NPD4965	Approved
0.8581	High Similarity	NPD6980	Clinical (unspecified phase)
0.8509	High Similarity	NPD6234	Discontinued
0.8428	Intermediate Similarity	NPD37	Approved
0.8242	Intermediate Similarity	NPD6232	Discontinued
0.8155	Intermediate Similarity	NPD7228	Approved
0.8153	Intermediate Similarity	NPD6143	Clinical (unspecified phase)
0.8107	Intermediate Similarity	NPD5844	Phase 1
0.8095	Intermediate Similarity	NPD7473	Discontinued
0.8072	Intermediate Similarity	NPD7199	Phase 2
0.7976	Intermediate Similarity	NPD7184	Clinical (unspecified phase)
0.7965	Intermediate Similarity	NPD7240	Approved
0.7829	Intermediate Similarity	NPD7090	Clinical (unspecified phase)
0.7692	Intermediate Similarity	NPD5494	Approved
0.7657	Intermediate Similarity	NPD6559	Discontinued
0.7654	Intermediate Similarity	NPD2534	Approved
0.7654	Intermediate Similarity	NPD2532	Approved
0.7654	Intermediate Similarity	NPD2533	Approved
0.7633	Intermediate Similarity	NPD919	Approved
0.7619	Intermediate Similarity	NPD4868	Clinical (unspecified phase)
0.7556	Intermediate Similarity	NPD8397	Clinical (unspecified phase)
0.7532	Intermediate Similarity	NPD3748	Approved
0.7529	Intermediate Similarity	NPD3818	Discontinued
0.75	Intermediate Similarity	NPD7819	Suspended
0.75	Intermediate Similarity	NPD1465	Phase 2
0.7486	Intermediate Similarity	NPD8055	Clinical (unspecified phase)
0.7484	Intermediate Similarity	NPD2438	Suspended
0.7467	Intermediate Similarity	NPD3705	Approved
0.7467	Intermediate Similarity	NPD1281	Approved
0.7456	Intermediate Similarity	NPD3817	Phase 2
0.7447	Intermediate Similarity	NPD7680	Approved
0.7394	Intermediate Similarity	NPD5006	Approved
0.7394	Intermediate Similarity	NPD5005	Approved
0.7389	Intermediate Similarity	NPD2979	Phase 3
0.7372	Intermediate Similarity	NPD3764	Approved
0.7356	Intermediate Similarity	NPD3926	Phase 2
0.7356	Intermediate Similarity	NPD5242	Approved
0.7342	Intermediate Similarity	NPD1933	Approved
0.7341	Intermediate Similarity	NPD6959	Discontinued
0.7341	Intermediate Similarity	NPD1247	Approved
0.7337	Intermediate Similarity	NPD1934	Approved
0.7326	Intermediate Similarity	NPD7237	Clinical (unspecified phase)
0.732	Intermediate Similarity	NPD1283	Approved
0.731	Intermediate Similarity	NPD3882	Suspended
0.731	Intermediate Similarity	NPD7768	Phase 2
0.7301	Intermediate Similarity	NPD3750	Approved
0.7299	Intermediate Similarity	NPD7229	Phase 3
0.7294	Intermediate Similarity	NPD2393	Clinical (unspecified phase)
0.7284	Intermediate Similarity	NPD970	Clinical (unspecified phase)
0.7273	Intermediate Similarity	NPD4420	Approved
0.7267	Intermediate Similarity	NPD3749	Approved
0.7262	Intermediate Similarity	NPD7458	Discontinued
0.7262	Intermediate Similarity	NPD5808	Clinical (unspecified phase)
0.7247	Intermediate Similarity	NPD7074	Phase 3
0.7246	Intermediate Similarity	NPD920	Approved
0.7239	Intermediate Similarity	NPD1243	Approved
0.7233	Intermediate Similarity	NPD230	Phase 1
0.7222	Intermediate Similarity	NPD4338	Clinical (unspecified phase)
0.7219	Intermediate Similarity	NPD6599	Discontinued
0.7219	Intermediate Similarity	NPD7028	Phase 2
0.7197	Intermediate Similarity	NPD5952	Clinical (unspecified phase)
0.7195	Intermediate Similarity	NPD7003	Approved
0.7195	Intermediate Similarity	NPD4628	Phase 3
0.7193	Intermediate Similarity	NPD7096	Clinical (unspecified phase)
0.7193	Intermediate Similarity	NPD2801	Approved
0.7191	Intermediate Similarity	NPD7054	Approved
0.7189	Intermediate Similarity	NPD7879	Clinical (unspecified phase)
0.7182	Intermediate Similarity	NPD8313	Approved
0.7182	Intermediate Similarity	NPD8312	Approved
0.7176	Intermediate Similarity	NPD7411	Suspended
0.7165	Intermediate Similarity	NPD8151	Discontinued
0.716	Intermediate Similarity	NPD3226	Approved
0.716	Intermediate Similarity	NPD2531	Phase 2
0.7152	Intermediate Similarity	NPD1651	Approved
0.7151	Intermediate Similarity	NPD5353	Approved
0.7151	Intermediate Similarity	NPD7472	Approved
0.7134	Intermediate Similarity	NPD7421	Clinical (unspecified phase)
0.7126	Intermediate Similarity	NPD642	Clinical (unspecified phase)
0.7119	Intermediate Similarity	NPD6166	Phase 2
0.7119	Intermediate Similarity	NPD6168	Clinical (unspecified phase)
0.7119	Intermediate Similarity	NPD6167	Clinical (unspecified phase)
0.7117	Intermediate Similarity	NPD2346	Discontinued
0.7111	Intermediate Similarity	NPD7993	Clinical (unspecified phase)
0.7108	Intermediate Similarity	NPD643	Clinical (unspecified phase)
0.7102	Intermediate Similarity	NPD5710	Approved
0.7102	Intermediate Similarity	NPD5711	Approved
0.7093	Intermediate Similarity	NPD8455	Phase 2
0.7083	Intermediate Similarity	NPD6273	Approved
0.7076	Intermediate Similarity	NPD6386	Approved
0.7076	Intermediate Similarity	NPD6385	Approved
0.7072	Intermediate Similarity	NPD7685	Pre-registration
0.7069	Intermediate Similarity	NPD7075	Discontinued
0.7066	Intermediate Similarity	NPD6799	Approved
0.7055	Intermediate Similarity	NPD2796	Approved
0.7039	Intermediate Similarity	NPD5691	Approved
0.7035	Intermediate Similarity	NPD6801	Discontinued
0.7033	Intermediate Similarity	NPD7808	Phase 3
0.703	Intermediate Similarity	NPD6674	Discontinued
0.7024	Intermediate Similarity	NPD7004	Clinical (unspecified phase)
0.7022	Intermediate Similarity	NPD7852	Clinical (unspecified phase)
0.7017	Intermediate Similarity	NPD6797	Phase 2
0.6994	Remote Similarity	NPD1509	Clinical (unspecified phase)
0.6988	Remote Similarity	NPD1878	Clinical (unspecified phase)
0.6988	Remote Similarity	NPD6398	Clinical (unspecified phase)
0.6978	Remote Similarity	NPD7251	Discontinued
0.6971	Remote Similarity	NPD4381	Clinical (unspecified phase)
0.6964	Remote Similarity	NPD1511	Approved
0.6954	Remote Similarity	NPD8443	Clinical (unspecified phase)
0.6951	Remote Similarity	NPD5405	Approved
0.6951	Remote Similarity	NPD5408	Approved
0.6951	Remote Similarity	NPD2935	Discontinued
0.6951	Remote Similarity	NPD5404	Approved
0.6951	Remote Similarity	NPD5406	Approved
0.6951	Remote Similarity	NPD1551	Phase 2
0.6949	Remote Similarity	NPD8127	Discontinued
0.6937	Remote Similarity	NPD6859	Clinical (unspecified phase)
0.6923	Remote Similarity	NPD4378	Clinical (unspecified phase)
0.6923	Remote Similarity	NPD7422	Clinical (unspecified phase)
0.6919	Remote Similarity	NPD4380	Phase 2
0.6909	Remote Similarity	NPD2343	Clinical (unspecified phase)
0.6906	Remote Similarity	NPD7804	Clinical (unspecified phase)
0.6894	Remote Similarity	NPD8032	Phase 2
0.689	Remote Similarity	NPD1510	Phase 2
0.6886	Remote Similarity	NPD4110	Phase 3
0.6886	Remote Similarity	NPD4109	Clinical (unspecified phase)
0.6884	Remote Similarity	NPD7827	Phase 1
0.6883	Remote Similarity	NPD17	Approved
0.6882	Remote Similarity	NPD1940	Clinical (unspecified phase)
0.6882	Remote Similarity	NPD1512	Approved
0.6879	Remote Similarity	NPD6873	Phase 2
0.6879	Remote Similarity	NPD1876	Approved
0.6875	Remote Similarity	NPD3027	Phase 3
0.6871	Remote Similarity	NPD1607	Approved
0.6864	Remote Similarity	NPD7390	Discontinued
0.6857	Remote Similarity	NPD5402	Approved
0.6852	Remote Similarity	NPD4307	Phase 2
0.6851	Remote Similarity	NPD7177	Discontinued
0.6851	Remote Similarity	NPD3751	Discontinued
0.6837	Remote Similarity	NPD7999	Approved
0.6834	Remote Similarity	NPD7782	Clinical (unspecified phase)
0.6834	Remote Similarity	NPD7783	Phase 2
0.6824	Remote Similarity	NPD5401	Approved
0.6824	Remote Similarity	NPD7410	Clinical (unspecified phase)
0.6821	Remote Similarity	NPD7435	Discontinued
0.6816	Remote Similarity	NPD3787	Discontinued
0.681	Remote Similarity	NPD447	Suspended
0.6807	Remote Similarity	NPD1552	Clinical (unspecified phase)
0.6807	Remote Similarity	NPD1550	Clinical (unspecified phase)
0.6802	Remote Similarity	NPD1653	Approved
0.6797	Remote Similarity	NPD5536	Phase 2
0.6793	Remote Similarity	NPD7038	Approved
0.6793	Remote Similarity	NPD7039	Approved
0.6788	Remote Similarity	NPD2799	Discontinued
0.678	Remote Similarity	NPD6971	Discontinued
0.6774	Remote Similarity	NPD4626	Approved
0.677	Remote Similarity	NPD4625	Phase 3
0.6766	Remote Similarity	NPD1549	Phase 2
0.6761	Remote Similarity	NPD4288	Approved
0.6758	Remote Similarity	NPD7893	Clinical (unspecified phase)
0.6755	Remote Similarity	NPD5283	Phase 1
0.6753	Remote Similarity	NPD6778	Approved
0.6753	Remote Similarity	NPD6776	Approved
0.6753	Remote Similarity	NPD6781	Approved
0.6753	Remote Similarity	NPD6780	Approved
0.6753	Remote Similarity	NPD6782	Approved
0.6753	Remote Similarity	NPD6777	Approved
0.6753	Remote Similarity	NPD6779	Approved
0.6752	Remote Similarity	NPD2981	Phase 2
0.6752	Remote Similarity	NPD3972	Approved
0.6752	Remote Similarity	NPD1608	Approved
0.6748	Remote Similarity	NPD1240	Approved
0.6746	Remote Similarity	NPD6190	Approved
0.6746	Remote Similarity	NPD5084	Clinical (unspecified phase)
0.6744	Remote Similarity	NPD5403	Approved
0.6728	Remote Similarity	NPD4907	Clinical (unspecified phase)
0.6728	Remote Similarity	NPD6798	Discontinued
0.6726	Remote Similarity	NPD2800	Approved
0.6723	Remote Similarity	NPD5019	Clinical (unspecified phase)
0.6709	Remote Similarity	NPD2982	Phase 2
0.6709	Remote Similarity	NPD2983	Phase 2
0.6708	Remote Similarity	NPD6832	Phase 2
0.6707	Remote Similarity	NPD1899	Clinical (unspecified phase)
0.6707	Remote Similarity	NPD7266	Discontinued
0.6704	Remote Similarity	NPD6746	Phase 2
0.6701	Remote Similarity	NPD7870	Phase 2
0.6701	Remote Similarity	NPD7871	Phase 2
0.6688	Remote Similarity	NPD1611	Approved
0.6687	Remote Similarity	NPD4308	Phase 3
0.6687	Remote Similarity	NPD6233	Phase 2
0.6686	Remote Similarity	NPD8166	Discontinued
0.6684	Remote Similarity	NPD6823	Phase 2
0.6667	Remote Similarity	NPD4357	Discontinued
0.6667	Remote Similarity	NPD5616	Clinical (unspecified phase)
0.6667	Remote Similarity	NPD5978	Approved
0.6667	Remote Similarity	NPD5977	Approved
0.665	Remote Similarity	NPD7698	Approved
0.665	Remote Similarity	NPD7696	Phase 3
0.665	Remote Similarity	NPD7697	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