NPASS Compound

Structure

Physi-Chem Properties

Molecular Weight:	220.07
Volume:	220.974
LogP:	2.679
LogD:	2.893
LogS:	-2.712
# Rotatable Bonds:	3
TPSA:	51.83
# H-Bond Aceptor:	4
# H-Bond Donor:	1
# Rings:	2
# Heavy Atoms:	4

MedChem Properties

QED Drug-Likeness Score:	0.864
Synthetic Accessibility Score:	2.959
Fsp3:	0.167
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Accepted
GSK Rule:	Accepted
BMS Rule:	0
Golden Triangle Rule:	Accepted
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-4.713
MDCK Permeability:	1.7110287444666028e-05
Pgp-inhibitor:	0.284
Pgp-substrate:	0.001
Human Intestinal Absorption (HIA):	0.01
20% Bioavailability (F20%):	0.002
30% Bioavailability (F30%):	0.002

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.079
Plasma Protein Binding (PPB):	88.7629623413086%
Volume Distribution (VD):	1.005
Pgp-substrate:	15.744402885437012%

ADMET: Metabolism

CYP1A2-inhibitor:	0.965
CYP1A2-substrate:	0.914
CYP2C19-inhibitor:	0.094
CYP2C19-substrate:	0.797
CYP2C9-inhibitor:	0.275
CYP2C9-substrate:	0.884
CYP2D6-inhibitor:	0.32
CYP2D6-substrate:	0.875
CYP3A4-inhibitor:	0.103
CYP3A4-substrate:	0.242

ADMET: Excretion

Clearance (CL):	10.957
Half-life (T1/2):	0.725

ADMET: Toxicity

hERG Blockers:	0.003
Human Hepatotoxicity (H-HT):	0.558
Drug-inuced Liver Injury (DILI):	0.968
AMES Toxicity:	0.14
Rat Oral Acute Toxicity:	0.944
Maximum Recommended Daily Dose:	0.35
Skin Sensitization:	0.656
Carcinogencity:	0.803
Eye Corrosion:	0.114
Eye Irritation:	0.781
Respiratory Toxicity:	0.612

Download Data

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

Natural Product: NPC160425

Natural Product ID:	NPC160425
*Common Name:**	(Z)-3-Ethylidene-6,7-Dimethoxyphthalide
IUPAC Name:	(3Z)-3-ethylidene-6,7-dimethoxy-2-benzofuran-1-one
Synonyms:
Standard InCHIKey:	TWRVIBBQOKJIPK-YWEYNIOJSA-N
Standard InCHI:	InChI=1S/C12H12O4/c1-4-8-7-5-6-9(14-2)11(15-3)10(7)12(13)16-8/h4-6H,1-3H3/b8-4-
SMILES:	C/C=C1/c2ccc(c(c2C(=O)O1)OC)OC
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL508455
PubChem CID:	25135577
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0004191] Isocoumarans [CHEMONTID:0003409] Isobenzofuranones

*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
NPO9098.1	Pittosporum illicioides	Under-species	n.a.	n.a.	n.a.	n.a.	n.a.	PMID[18817445]
NPO1592	Citrullus colocynthis	Species	Cucurbitaceae	Eukaryota	Fruits	n.a.	n.a.	PMID[30183289]
NPO1592	Citrullus colocynthis	Species	Cucurbitaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO1592	Citrullus colocynthis	Species	Cucurbitaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO1592	Citrullus colocynthis	Species	Cucurbitaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO9098	Pittosporum illicioides	Species	Pittosporaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO10206	Anthemis fuscata	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO10606	Pteris japonica	Species	Pteridaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO1592	Citrullus colocynthis	Species	Cucurbitaceae	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	2

Activity Type	# Activity
NON-MOLECULAR	2

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT20529	NON-MOLECULAR	NON-PROTEIN TARGET	n.a.	IC50	>	50000.0	nM	PMID[475890]
NPT20529	NON-MOLECULAR	NON-PROTEIN TARGET	n.a.	IC50	=	33900.0	nM	PMID[475890]

☑ 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 NPC160425 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	385
0.1-0.2	1764
0.2-0.3	4783
0.3-0.4	10621
0.4-0.5	7103
0.5-0.6	3650
0.6-0.7	7803
0.7-0.8	6246
0.8-0.85	308
0.85-0.9	28
0.9-0.95	4
0.95-1	2

Similarity Score	Similarity Level	Natural Product ID
0.9847	High Similarity	NPC233780
0.9485	High Similarity	NPC258307
0.9281	High Similarity	NPC85734
0.9281	High Similarity	NPC32058
0.9275	High Similarity	NPC27106
0.8889	High Similarity	NPC96501
0.8841	High Similarity	NPC46947
0.8828	High Similarity	NPC473732
0.8767	High Similarity	NPC475116
0.8716	High Similarity	NPC301897
0.8652	High Similarity	NPC90411
0.8649	High Similarity	NPC79998
0.8649	High Similarity	NPC199926
0.8647	High Similarity	NPC154275
0.8623	High Similarity	NPC143649
0.8601	High Similarity	NPC470932
0.8591	High Similarity	NPC150227
0.8543	High Similarity	NPC78944
0.8533	High Similarity	NPC84935
0.8533	High Similarity	NPC77679
0.8533	High Similarity	NPC190020
0.8529	High Similarity	NPC473271
0.8529	High Similarity	NPC299010
0.8514	High Similarity	NPC295646
0.85	High Similarity	NPC62907
0.8489	Intermediate Similarity	NPC470844
0.8487	Intermediate Similarity	NPC15212
0.8478	Intermediate Similarity	NPC288743
0.8472	Intermediate Similarity	NPC184702
0.8462	Intermediate Similarity	NPC297985
0.8456	Intermediate Similarity	NPC281477
0.8446	Intermediate Similarity	NPC240768
0.8446	Intermediate Similarity	NPC200773
0.8429	Intermediate Similarity	NPC77955
0.8429	Intermediate Similarity	NPC209229
0.8421	Intermediate Similarity	NPC47623
0.8421	Intermediate Similarity	NPC200594
0.8414	Intermediate Similarity	NPC224687
0.84	Intermediate Similarity	NPC82592
0.84	Intermediate Similarity	NPC16082
0.8394	Intermediate Similarity	NPC285776
0.838	Intermediate Similarity	NPC134969
0.838	Intermediate Similarity	NPC471819
0.8378	Intermediate Similarity	NPC179178
0.8369	Intermediate Similarity	NPC157944
0.8369	Intermediate Similarity	NPC474274
0.8369	Intermediate Similarity	NPC135837
0.8358	Intermediate Similarity	NPC470163
0.8358	Intermediate Similarity	NPC470162
0.8357	Intermediate Similarity	NPC180905
0.8357	Intermediate Similarity	NPC182496
0.8356	Intermediate Similarity	NPC260946
0.8345	Intermediate Similarity	NPC23955
0.8344	Intermediate Similarity	NPC227062
0.8344	Intermediate Similarity	NPC115123
0.8344	Intermediate Similarity	NPC239113
0.8344	Intermediate Similarity	NPC54928
0.8322	Intermediate Similarity	NPC50823
0.8322	Intermediate Similarity	NPC104353
0.8312	Intermediate Similarity	NPC144843
0.831	Intermediate Similarity	NPC44573
0.8299	Intermediate Similarity	NPC117463
0.8298	Intermediate Similarity	NPC326847
0.8289	Intermediate Similarity	NPC143328
0.8289	Intermediate Similarity	NPC19600
0.8288	Intermediate Similarity	NPC296575
0.8288	Intermediate Similarity	NPC136278
0.8288	Intermediate Similarity	NPC474446
0.8286	Intermediate Similarity	NPC155098
0.8286	Intermediate Similarity	NPC311339
0.8278	Intermediate Similarity	NPC38898
0.8276	Intermediate Similarity	NPC9966
0.8276	Intermediate Similarity	NPC70853
0.8267	Intermediate Similarity	NPC292460
0.8264	Intermediate Similarity	NPC58229
0.8255	Intermediate Similarity	NPC216917
0.8252	Intermediate Similarity	NPC275356
0.8243	Intermediate Similarity	NPC183236
0.8243	Intermediate Similarity	NPC476058
0.8239	Intermediate Similarity	NPC14022
0.8231	Intermediate Similarity	NPC40818
0.8231	Intermediate Similarity	NPC24257
0.8231	Intermediate Similarity	NPC106461
0.8231	Intermediate Similarity	NPC231013
0.8231	Intermediate Similarity	NPC215932
0.8231	Intermediate Similarity	NPC153620
0.8231	Intermediate Similarity	NPC138978
0.8231	Intermediate Similarity	NPC110639
0.8231	Intermediate Similarity	NPC14958
0.8227	Intermediate Similarity	NPC211386
0.8224	Intermediate Similarity	NPC474983
0.8219	Intermediate Similarity	NPC280404
0.8219	Intermediate Similarity	NPC213900
0.8219	Intermediate Similarity	NPC86373
0.8219	Intermediate Similarity	NPC277426
0.8219	Intermediate Similarity	NPC210425
0.8219	Intermediate Similarity	NPC113089
0.8214	Intermediate Similarity	NPC283823
0.8214	Intermediate Similarity	NPC159418
0.8212	Intermediate Similarity	NPC244371
0.8212	Intermediate Similarity	NPC186507
0.8207	Intermediate Similarity	NPC474385
0.8207	Intermediate Similarity	NPC124467
0.8207	Intermediate Similarity	NPC214919
0.8207	Intermediate Similarity	NPC29536
0.82	Intermediate Similarity	NPC198615
0.82	Intermediate Similarity	NPC474170
0.82	Intermediate Similarity	NPC228662
0.82	Intermediate Similarity	NPC474388
0.82	Intermediate Similarity	NPC215921
0.82	Intermediate Similarity	NPC70016
0.82	Intermediate Similarity	NPC118332
0.82	Intermediate Similarity	NPC204350
0.82	Intermediate Similarity	NPC472535
0.8194	Intermediate Similarity	NPC207418
0.8194	Intermediate Similarity	NPC22324
0.8194	Intermediate Similarity	NPC51681
0.8188	Intermediate Similarity	NPC300983
0.8188	Intermediate Similarity	NPC198927
0.8188	Intermediate Similarity	NPC153547
0.8188	Intermediate Similarity	NPC474648
0.8182	Intermediate Similarity	NPC470962
0.8182	Intermediate Similarity	NPC197666
0.8182	Intermediate Similarity	NPC126739
0.8176	Intermediate Similarity	NPC85233
0.8176	Intermediate Similarity	NPC474999
0.8176	Intermediate Similarity	NPC205522
0.8163	Intermediate Similarity	NPC165512
0.8163	Intermediate Similarity	NPC472917
0.8163	Intermediate Similarity	NPC30890
0.8163	Intermediate Similarity	NPC213482
0.8158	Intermediate Similarity	NPC471800
0.8158	Intermediate Similarity	NPC276059
0.8158	Intermediate Similarity	NPC20541
0.8158	Intermediate Similarity	NPC34725
0.8158	Intermediate Similarity	NPC122623
0.8158	Intermediate Similarity	NPC241774
0.8158	Intermediate Similarity	NPC16286
0.8156	Intermediate Similarity	NPC37065
0.8156	Intermediate Similarity	NPC45404
0.8151	Intermediate Similarity	NPC51106
0.8151	Intermediate Similarity	NPC474036
0.8151	Intermediate Similarity	NPC472006
0.8151	Intermediate Similarity	NPC18211
0.8151	Intermediate Similarity	NPC143092
0.8146	Intermediate Similarity	NPC153008
0.8146	Intermediate Similarity	NPC271681
0.8146	Intermediate Similarity	NPC308555
0.8146	Intermediate Similarity	NPC199773
0.8146	Intermediate Similarity	NPC148497
0.8143	Intermediate Similarity	NPC111888
0.8141	Intermediate Similarity	NPC477689
0.8138	Intermediate Similarity	NPC1704
0.8138	Intermediate Similarity	NPC67650
0.8138	Intermediate Similarity	NPC475730
0.8138	Intermediate Similarity	NPC130485
0.8133	Intermediate Similarity	NPC469670
0.8133	Intermediate Similarity	NPC31132
0.8133	Intermediate Similarity	NPC29056
0.8133	Intermediate Similarity	NPC103509
0.8133	Intermediate Similarity	NPC119929
0.8133	Intermediate Similarity	NPC469619
0.8133	Intermediate Similarity	NPC177839
0.8125	Intermediate Similarity	NPC223336
0.8121	Intermediate Similarity	NPC55327
0.8121	Intermediate Similarity	NPC10304
0.8121	Intermediate Similarity	NPC63256
0.8117	Intermediate Similarity	NPC45846
0.8117	Intermediate Similarity	NPC238381
0.8117	Intermediate Similarity	NPC125713
0.8117	Intermediate Similarity	NPC325122
0.8112	Intermediate Similarity	NPC125417
0.8112	Intermediate Similarity	NPC25305
0.8112	Intermediate Similarity	NPC110899
0.8112	Intermediate Similarity	NPC95679
0.8112	Intermediate Similarity	NPC112068
0.8108	Intermediate Similarity	NPC310259
0.8108	Intermediate Similarity	NPC226987
0.8108	Intermediate Similarity	NPC283002
0.8108	Intermediate Similarity	NPC107625
0.8108	Intermediate Similarity	NPC216314
0.8108	Intermediate Similarity	NPC120924
0.8108	Intermediate Similarity	NPC143903
0.8108	Intermediate Similarity	NPC472033
0.8108	Intermediate Similarity	NPC302408
0.8108	Intermediate Similarity	NPC195919
0.8105	Intermediate Similarity	NPC257277
0.8105	Intermediate Similarity	NPC197751
0.8099	Intermediate Similarity	NPC72796
0.8099	Intermediate Similarity	NPC44245
0.8095	Intermediate Similarity	NPC257025
0.8095	Intermediate Similarity	NPC182842
0.8095	Intermediate Similarity	NPC293201
0.8095	Intermediate Similarity	NPC229787
0.8092	Intermediate Similarity	NPC478213
0.8092	Intermediate Similarity	NPC279930
0.8092	Intermediate Similarity	NPC144801
0.8092	Intermediate Similarity	NPC116850
0.8092	Intermediate Similarity	NPC291510
0.8092	Intermediate Similarity	NPC197188

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 NPC160425 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	332
0.1-0.2	981
0.2-0.3	1920
0.3-0.4	2649
0.4-0.5	1671
0.5-0.6	1031
0.6-0.7	438
0.7-0.8	121
0.8-0.85	7
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.8478	Intermediate Similarity	NPD447	Suspended
0.8252	Intermediate Similarity	NPD970	Clinical (unspecified phase)
0.8077	Intermediate Similarity	NPD6232	Discontinued
0.8041	Intermediate Similarity	NPD2533	Approved
0.8041	Intermediate Similarity	NPD2532	Approved
0.8041	Intermediate Similarity	NPD2534	Approved
0.8039	Intermediate Similarity	NPD3817	Phase 2
0.8	Intermediate Similarity	NPD919	Approved
0.7958	Intermediate Similarity	NPD1933	Approved
0.7949	Intermediate Similarity	NPD5494	Approved
0.7925	Intermediate Similarity	NPD7473	Discontinued
0.7871	Intermediate Similarity	NPD3882	Suspended
0.7857	Intermediate Similarity	NPD2801	Approved
0.7815	Intermediate Similarity	NPD920	Approved
0.7815	Intermediate Similarity	NPD6980	Clinical (unspecified phase)
0.7792	Intermediate Similarity	NPD1934	Approved
0.7785	Intermediate Similarity	NPD1247	Approved
0.7742	Intermediate Similarity	NPD1465	Phase 2
0.774	Intermediate Similarity	NPD2935	Discontinued
0.7737	Intermediate Similarity	NPD3705	Approved
0.7733	Intermediate Similarity	NPD1511	Approved
0.7714	Intermediate Similarity	NPD1019	Discontinued
0.7708	Intermediate Similarity	NPD1899	Clinical (unspecified phase)
0.7708	Intermediate Similarity	NPD230	Phase 1
0.7688	Intermediate Similarity	NPD3926	Phase 2
0.7681	Intermediate Similarity	NPD9717	Approved
0.7671	Intermediate Similarity	NPD3748	Approved
0.7632	Intermediate Similarity	NPD1512	Approved
0.7628	Intermediate Similarity	NPD7819	Suspended
0.7616	Intermediate Similarity	NPD6799	Approved
0.7616	Intermediate Similarity	NPD6143	Clinical (unspecified phase)
0.7606	Intermediate Similarity	NPD6832	Phase 2
0.7584	Intermediate Similarity	NPD1243	Approved
0.7568	Intermediate Similarity	NPD2346	Discontinued
0.7566	Intermediate Similarity	NPD642	Clinical (unspecified phase)
0.7564	Intermediate Similarity	NPD37	Approved
0.7546	Intermediate Similarity	NPD3818	Discontinued
0.7532	Intermediate Similarity	NPD4965	Approved
0.7532	Intermediate Similarity	NPD4966	Approved
0.7532	Intermediate Similarity	NPD4967	Phase 2
0.7516	Intermediate Similarity	NPD2393	Clinical (unspecified phase)
0.75	Intermediate Similarity	NPD5844	Phase 1
0.75	Intermediate Similarity	NPD411	Approved
0.75	Intermediate Similarity	NPD6385	Approved
0.75	Intermediate Similarity	NPD6386	Approved
0.7484	Intermediate Similarity	NPD3226	Approved
0.7438	Intermediate Similarity	NPD6234	Discontinued
0.7436	Intermediate Similarity	NPD6599	Discontinued
0.7434	Intermediate Similarity	NPD643	Clinical (unspecified phase)
0.7432	Intermediate Similarity	NPD651	Clinical (unspecified phase)
0.7432	Intermediate Similarity	NPD2799	Discontinued
0.7426	Intermediate Similarity	NPD9493	Approved
0.7421	Intermediate Similarity	NPD4868	Clinical (unspecified phase)
0.7417	Intermediate Similarity	NPD3750	Approved
0.7417	Intermediate Similarity	NPD1878	Clinical (unspecified phase)
0.7413	Intermediate Similarity	NPD9494	Approved
0.7397	Intermediate Similarity	NPD1240	Approved
0.7394	Intermediate Similarity	NPD1203	Approved
0.7391	Intermediate Similarity	NPD5691	Approved
0.7383	Intermediate Similarity	NPD1551	Phase 2
0.7383	Intermediate Similarity	NPD2796	Approved
0.7379	Intermediate Similarity	NPD3764	Approved
0.7379	Intermediate Similarity	NPD1699	Clinical (unspecified phase)
0.7375	Intermediate Similarity	NPD3749	Approved
0.7371	Intermediate Similarity	NPD4420	Approved
0.7362	Intermediate Similarity	NPD5242	Approved
0.7358	Intermediate Similarity	NPD5353	Approved
0.7358	Intermediate Similarity	NPD5402	Approved
0.7357	Intermediate Similarity	NPD1281	Approved
0.7351	Intermediate Similarity	NPD2800	Approved
0.7346	Intermediate Similarity	NPD7199	Phase 2
0.7338	Intermediate Similarity	NPD17	Approved
0.7321	Intermediate Similarity	NPD4338	Clinical (unspecified phase)
0.7317	Intermediate Similarity	NPD6166	Phase 2
0.7317	Intermediate Similarity	NPD6168	Clinical (unspecified phase)
0.7317	Intermediate Similarity	NPD6167	Clinical (unspecified phase)
0.7315	Intermediate Similarity	NPD1510	Phase 2
0.7301	Intermediate Similarity	NPD5710	Approved
0.7301	Intermediate Similarity	NPD5711	Approved
0.7297	Intermediate Similarity	NPD1607	Approved
0.7296	Intermediate Similarity	NPD7096	Clinical (unspecified phase)
0.7289	Intermediate Similarity	NPD7054	Approved
0.7267	Intermediate Similarity	NPD8397	Clinical (unspecified phase)
0.726	Intermediate Similarity	NPD2313	Discontinued
0.7256	Intermediate Similarity	NPD7184	Clinical (unspecified phase)
0.7246	Intermediate Similarity	NPD7074	Phase 3
0.7246	Intermediate Similarity	NPD5536	Phase 2
0.7246	Intermediate Similarity	NPD7472	Approved
0.7237	Intermediate Similarity	NPD2654	Approved
0.7233	Intermediate Similarity	NPD6801	Discontinued
0.7226	Intermediate Similarity	NPD4378	Clinical (unspecified phase)
0.7226	Intermediate Similarity	NPD5401	Approved
0.7219	Intermediate Similarity	NPD1471	Phase 3
0.7219	Intermediate Similarity	NPD1552	Clinical (unspecified phase)
0.7219	Intermediate Similarity	NPD1550	Clinical (unspecified phase)
0.7214	Intermediate Similarity	NPD4626	Approved
0.7207	Intermediate Similarity	NPD5005	Approved
0.7207	Intermediate Similarity	NPD5006	Approved
0.7203	Intermediate Similarity	NPD1876	Approved
0.7203	Intermediate Similarity	NPD1283	Approved
0.7194	Intermediate Similarity	NPD9545	Approved
0.719	Intermediate Similarity	NPD4628	Phase 3
0.7183	Intermediate Similarity	NPD1608	Approved
0.7179	Intermediate Similarity	NPD1940	Clinical (unspecified phase)
0.7171	Intermediate Similarity	NPD1549	Phase 2
0.7162	Intermediate Similarity	NPD943	Approved
0.7162	Intermediate Similarity	NPD2979	Phase 3
0.716	Intermediate Similarity	NPD7075	Discontinued
0.7152	Intermediate Similarity	NPD2438	Suspended
0.7143	Intermediate Similarity	NPD9268	Approved
0.7143	Intermediate Similarity	NPD1358	Approved
0.7143	Intermediate Similarity	NPD1296	Phase 2
0.7143	Intermediate Similarity	NPD6859	Clinical (unspecified phase)
0.7134	Intermediate Similarity	NPD5403	Approved
0.7126	Intermediate Similarity	NPD7228	Approved
0.7118	Intermediate Similarity	NPD7808	Phase 3
0.7115	Intermediate Similarity	NPD3146	Approved
0.7115	Intermediate Similarity	NPD3688	Clinical (unspecified phase)
0.7113	Intermediate Similarity	NPD1547	Clinical (unspecified phase)
0.7108	Intermediate Similarity	NPD2403	Approved
0.7107	Intermediate Similarity	NPD4380	Phase 2
0.7105	Intermediate Similarity	NPD2344	Approved
0.7103	Intermediate Similarity	NPD2798	Approved
0.7101	Intermediate Similarity	NPD6797	Phase 2
0.7099	Intermediate Similarity	NPD7768	Phase 2
0.7099	Intermediate Similarity	NPD9261	Approved
0.708	Intermediate Similarity	NPD1241	Discontinued
0.708	Intermediate Similarity	NPD5283	Phase 1
0.7078	Intermediate Similarity	NPD4109	Clinical (unspecified phase)
0.7078	Intermediate Similarity	NPD4110	Phase 3
0.7063	Intermediate Similarity	NPD9269	Phase 2
0.7063	Intermediate Similarity	NPD7411	Suspended
0.7059	Intermediate Similarity	NPD6559	Discontinued
0.7059	Intermediate Similarity	NPD7251	Discontinued
0.7047	Intermediate Similarity	NPD4307	Phase 2
0.7045	Intermediate Similarity	NPD164	Approved
0.7034	Intermediate Similarity	NPD3267	Approved
0.7034	Intermediate Similarity	NPD3266	Approved
0.703	Intermediate Similarity	NPD6959	Discontinued
0.703	Intermediate Similarity	NPD8127	Discontinued
0.7021	Intermediate Similarity	NPD1651	Approved
0.7013	Intermediate Similarity	NPD7421	Clinical (unspecified phase)
0.7	Intermediate Similarity	NPD6355	Discontinued
0.6994	Remote Similarity	NPD8055	Clinical (unspecified phase)
0.6993	Remote Similarity	NPD422	Phase 1
0.6993	Remote Similarity	NPD2343	Clinical (unspecified phase)
0.6985	Remote Similarity	NPD2181	Clinical (unspecified phase)
0.6975	Remote Similarity	NPD1006	Clinical (unspecified phase)
0.6972	Remote Similarity	NPD1778	Approved
0.6963	Remote Similarity	NPD2182	Approved
0.6959	Remote Similarity	NPD7240	Approved
0.6959	Remote Similarity	NPD7685	Pre-registration
0.6957	Remote Similarity	NPD6873	Phase 2
0.6951	Remote Similarity	NPD4381	Clinical (unspecified phase)
0.6939	Remote Similarity	NPD3018	Phase 2
0.6934	Remote Similarity	NPD228	Approved
0.6929	Remote Similarity	NPD405	Clinical (unspecified phase)
0.6928	Remote Similarity	NPD5408	Approved
0.6928	Remote Similarity	NPD5404	Approved
0.6928	Remote Similarity	NPD5405	Approved
0.6928	Remote Similarity	NPD5406	Approved
0.6923	Remote Similarity	NPD2309	Approved
0.6923	Remote Similarity	NPD3496	Discontinued
0.6918	Remote Similarity	NPD2797	Approved
0.6918	Remote Similarity	NPD1470	Approved
0.6909	Remote Similarity	NPD5537	Clinical (unspecified phase)
0.6901	Remote Similarity	NPD7993	Clinical (unspecified phase)
0.6897	Remote Similarity	NPD4379	Clinical (unspecified phase)
0.6893	Remote Similarity	NPD7879	Clinical (unspecified phase)
0.6892	Remote Similarity	NPD1529	Clinical (unspecified phase)
0.6892	Remote Similarity	NPD1008	Clinical (unspecified phase)
0.6889	Remote Similarity	NPD9263	Approved
0.6889	Remote Similarity	NPD9264	Approved
0.6889	Remote Similarity	NPD9267	Approved
0.6886	Remote Similarity	NPD7229	Phase 3
0.6883	Remote Similarity	NPD6005	Phase 3
0.6883	Remote Similarity	NPD6004	Phase 3
0.6883	Remote Similarity	NPD6003	Clinical (unspecified phase)
0.6883	Remote Similarity	NPD6002	Phase 3
0.6883	Remote Similarity	NPD6006	Clinical (unspecified phase)
0.6879	Remote Similarity	NPD8313	Approved
0.6879	Remote Similarity	NPD8312	Approved
0.6875	Remote Similarity	NPD1201	Approved
0.6875	Remote Similarity	NPD1653	Approved
0.6875	Remote Similarity	NPD1611	Approved
0.6867	Remote Similarity	NPD8032	Phase 2
0.6863	Remote Similarity	NPD4308	Phase 3
0.6863	Remote Similarity	NPD1509	Clinical (unspecified phase)
0.6859	Remote Similarity	NPD7003	Approved
0.6859	Remote Similarity	NPD6398	Clinical (unspecified phase)
0.6855	Remote Similarity	NPD6273	Approved
0.6846	Remote Similarity	NPD3027	Phase 3
0.6838	Remote Similarity	NPD74	Approved
0.6838	Remote Similarity	NPD9266	Approved
0.6832	Remote Similarity	NPD5808	Clinical (unspecified phase)
0.6829	Remote Similarity	NPD4288	Approved
0.6829	Remote Similarity	NPD5977	Approved
0.6829	Remote Similarity	NPD8443	Clinical (unspecified phase)
0.6829	Remote Similarity	NPD5978	Approved
0.6828	Remote Similarity	NPD2981	Phase 2

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