NPASS Compound

Structure

Physi-Chem Properties

Molecular Weight:	196.07
Volume:	197.575
LogP:	2.819
LogD:	1.543
LogS:	-2.896
# Rotatable Bonds:	2
TPSA:	66.76
# H-Bond Aceptor:	4
# H-Bond Donor:	2
# Rings:	1
# Heavy Atoms:	4

MedChem Properties

QED Drug-Likeness Score:	0.755
Synthetic Accessibility Score:	2.109
Fsp3:	0.3
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Accepted
GSK Rule:	Accepted
BMS Rule:	0
Golden Triangle Rule:	Rejected
Chelating Alert:	1
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-5.001
MDCK Permeability:	7.571265996375587e-06
Pgp-inhibitor:	0.001
Pgp-substrate:	0.017
Human Intestinal Absorption (HIA):	0.013
20% Bioavailability (F20%):	0.006
30% Bioavailability (F30%):	0.003

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.143
Plasma Protein Binding (PPB):	91.71375274658203%
Volume Distribution (VD):	0.481
Pgp-substrate:	6.202428340911865%

ADMET: Metabolism

CYP1A2-inhibitor:	0.082
CYP1A2-substrate:	0.884
CYP2C19-inhibitor:	0.032
CYP2C19-substrate:	0.068
CYP2C9-inhibitor:	0.038
CYP2C9-substrate:	0.135
CYP2D6-inhibitor:	0.022
CYP2D6-substrate:	0.15
CYP3A4-inhibitor:	0.02
CYP3A4-substrate:	0.105

ADMET: Excretion

Clearance (CL):	5.453
Half-life (T1/2):	0.884

ADMET: Toxicity

hERG Blockers:	0.024
Human Hepatotoxicity (H-HT):	0.367
Drug-inuced Liver Injury (DILI):	0.858
AMES Toxicity:	0.013
Rat Oral Acute Toxicity:	0.69
Maximum Recommended Daily Dose:	0.024
Skin Sensitization:	0.194
Carcinogencity:	0.092
Eye Corrosion:	0.01
Eye Irritation:	0.944
Respiratory Toxicity:	0.745

Download Data

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

Natural Product: NPC165172

Natural Product ID:	NPC165172
*Common Name:**	2-Hydroxy-4-Methoxy-3,6-Dimethylbenzoic Acid
IUPAC Name:	2-hydroxy-4-methoxy-3,6-dimethylbenzoic acid
Synonyms:
Standard InCHIKey:	BMRVNZZVDSVOQG-UHFFFAOYSA-N
Standard InCHI:	InChI=1S/C10H12O4/c1-5-4-7(14-3)6(2)9(11)8(5)10(12)13/h4,11H,1-3H3,(H,12,13)
SMILES:	COc1cc(C)c(c(c1C)O)C(=O)O
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL2227774
PubChem CID:	3083580
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0002448] Benzenoids [CHEMONTID:0002279] Benzene and substituted derivatives [CHEMONTID:0000176] Benzoic acids and derivatives [CHEMONTID:0002344] Methoxybenzoic acids and derivatives [CHEMONTID:0002346] P-methoxybenzoic acids and derivatives

*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
NPO20034	Hyattella intestinalis	Species	Spongiidae	Eukaryota	n.a.	Inner Gneerings, a group of shoals off Mooloolaba (Australia)	2005-JUL	PMID[17125226]
NPO29118	Euonymus alatus	Species	Celastraceae	Eukaryota	leaves and twigs	n.a.	n.a.	PMID[21435874]
NPO29118	Euonymus alatus	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO2602	Usnea longissima	Species	Parmeliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO23042	Rhizocarpon geographicum	Species	Rhizocarpaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO29118	Euonymus alatus	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO7458	Evernia prunastri	Species	Parmeliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO2602	Usnea longissima	Species	Parmeliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO29118	Euonymus alatus	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO29118	Euonymus alatus	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO17038	Linum sativum	Species	Linaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO20034	Hyattella intestinalis	Species	Spongiidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO22985	Thamnosma montana	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO24220	Inocybe umbrina	Species	Inocybaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO23042	Rhizocarpon geographicum	Species	Rhizocarpaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO16394	Coniocarpon cinnabarinum	Species	Arthoniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO23347	Piper fadyenii	Species	Piperaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO2602	Usnea longissima	Species	Parmeliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO7458	Evernia prunastri	Species	Parmeliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO29118	Euonymus alatus	Species	Celastraceae	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	6
Others	18

Activity Type	# Activity
Organism	24

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT2701	Organism	Pythium debaryanum	Pythium debaryanum	ED50	=	73.8	ug ml-1	PMID[452646]
NPT961	Organism	Pythium aphanidermatum	Pythium aphanidermatum	ED50	=	71.11	ug ml-1	PMID[452646]
NPT2702	Organism	Fusarium udum	Fusarium udum	ED50	=	106.13	ug ml-1	PMID[452646]
NPT2703	Organism	Rhizoctonia bataticola	Rhizoctonia bataticola	ED50	=	74.48	ug ml-1	PMID[452646]
NPT529	Organism	Rhizoctonia solani	Rhizoctonia solani	ED50	=	50.65	ug ml-1	PMID[452646]
NPT722	Organism	Athelia rolfsii	Athelia rolfsii	ED50	=	115.56	ug ml-1	PMID[452646]
NPT2701	Organism	Pythium debaryanum	Pythium debaryanum	Inhibition	=	33.0	%	PMID[452646]
NPT2701	Organism	Pythium debaryanum	Pythium debaryanum	Inhibition	=	61.4	%	PMID[452646]
NPT2701	Organism	Pythium debaryanum	Pythium debaryanum	Inhibition	=	83.83	%	PMID[452646]
NPT961	Organism	Pythium aphanidermatum	Pythium aphanidermatum	Inhibition	=	28.36	%	PMID[452646]
NPT961	Organism	Pythium aphanidermatum	Pythium aphanidermatum	Inhibition	=	67.66	%	PMID[452646]
NPT961	Organism	Pythium aphanidermatum	Pythium aphanidermatum	Inhibition	=	79.33	%	PMID[452646]
NPT2702	Organism	Fusarium udum	Fusarium udum	Inhibition	=	23.66	%	PMID[452646]
NPT2702	Organism	Fusarium udum	Fusarium udum	Inhibition	=	46.46	%	PMID[452646]
NPT2702	Organism	Fusarium udum	Fusarium udum	Inhibition	=	58.0	%	PMID[452646]
NPT2703	Organism	Rhizoctonia bataticola	Rhizoctonia bataticola	Inhibition	=	39.4	%	PMID[452646]
NPT2703	Organism	Rhizoctonia bataticola	Rhizoctonia bataticola	Inhibition	=	56.4	%	PMID[452646]
NPT2703	Organism	Rhizoctonia bataticola	Rhizoctonia bataticola	Inhibition	=	68.0	%	PMID[452646]
NPT529	Organism	Rhizoctonia solani	Rhizoctonia solani	Inhibition	=	50.0	%	PMID[452646]
NPT529	Organism	Rhizoctonia solani	Rhizoctonia solani	Inhibition	=	70.6	%	PMID[452646]
NPT529	Organism	Rhizoctonia solani	Rhizoctonia solani	Inhibition	=	82.0	%	PMID[452646]
NPT722	Organism	Athelia rolfsii	Athelia rolfsii	Inhibition	=	28.36	%	PMID[452646]
NPT722	Organism	Athelia rolfsii	Athelia rolfsii	Inhibition	=	44.3	%	PMID[452646]
NPT722	Organism	Athelia rolfsii	Athelia rolfsii	Inhibition	=	53.0	%	PMID[452646]

☑ 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 NPC165172 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	352
0.1-0.2	1691
0.2-0.3	4048
0.3-0.4	9623
0.4-0.5	8733
0.5-0.6	3627
0.6-0.7	6131
0.7-0.8	6216
0.8-0.85	1704
0.85-0.9	452
0.9-0.95	110
0.95-1	10

Similarity Score	Similarity Level	Natural Product ID
0.9699	High Similarity	NPC158481
0.9624	High Similarity	NPC182496
0.9624	High Similarity	NPC180905
0.9568	High Similarity	NPC225173
0.9568	High Similarity	NPC163846
0.95	High Similarity	NPC125801
0.9481	High Similarity	NPC135837
0.942	High Similarity	NPC94076
0.942	High Similarity	NPC182255
0.9416	High Similarity	NPC99441
0.9366	High Similarity	NPC233267
0.9366	High Similarity	NPC291049
0.9353	High Similarity	NPC84266
0.9348	High Similarity	NPC67650
0.9348	High Similarity	NPC1704
0.9348	High Similarity	NPC37530
0.9338	High Similarity	NPC194579
0.9323	High Similarity	NPC189823
0.9323	High Similarity	NPC219892
0.9301	High Similarity	NPC119929
0.9296	High Similarity	NPC37139
0.9296	High Similarity	NPC105415
0.9281	High Similarity	NPC250755
0.9265	High Similarity	NPC50455
0.9248	High Similarity	NPC296158
0.9236	High Similarity	NPC133856
0.922	High Similarity	NPC473692
0.922	High Similarity	NPC75694
0.9214	High Similarity	NPC51106
0.9214	High Similarity	NPC472006
0.9214	High Similarity	NPC159721
0.9214	High Similarity	NPC469542
0.9209	High Similarity	NPC90411
0.9209	High Similarity	NPC475730
0.9185	High Similarity	NPC153783
0.9172	High Similarity	NPC175978
0.9172	High Similarity	NPC271681
0.9172	High Similarity	NPC273483
0.9167	High Similarity	NPC150928
0.9167	High Similarity	NPC158866
0.9161	High Similarity	NPC2569
0.9161	High Similarity	NPC172329
0.9155	High Similarity	NPC260946
0.9149	High Similarity	NPC151607
0.9149	High Similarity	NPC42540
0.9143	High Similarity	NPC474385
0.9118	High Similarity	NPC175943
0.911	High Similarity	NPC472799
0.9098	High Similarity	NPC293453
0.9091	High Similarity	NPC289042
0.9091	High Similarity	NPC312929
0.9091	High Similarity	NPC56433
0.9091	High Similarity	NPC22005
0.9091	High Similarity	NPC123202
0.9091	High Similarity	NPC190648
0.9091	High Similarity	NPC137296
0.9091	High Similarity	NPC245584
0.9091	High Similarity	NPC8817
0.9091	High Similarity	NPC126767
0.9091	High Similarity	NPC118027
0.9091	High Similarity	NPC34802
0.9091	High Similarity	NPC7943
0.9085	High Similarity	NPC28632
0.9085	High Similarity	NPC134621
0.9078	High Similarity	NPC471731
0.9071	High Similarity	NPC220106
0.9065	High Similarity	NPC88269
0.9065	High Similarity	NPC275356
0.9058	High Similarity	NPC70380
0.9051	High Similarity	NPC278375
0.9048	High Similarity	NPC89625
0.9048	High Similarity	NPC149618
0.9044	High Similarity	NPC180261
0.9044	High Similarity	NPC48036
0.9044	High Similarity	NPC37299
0.9041	High Similarity	NPC217447
0.9034	High Similarity	NPC325983
0.903	High Similarity	NPC230818
0.9028	High Similarity	NPC256672
0.9028	High Similarity	NPC27221
0.9028	High Similarity	NPC7025
0.9021	High Similarity	NPC470357
0.9021	High Similarity	NPC138978
0.9021	High Similarity	NPC267509
0.9021	High Similarity	NPC237208
0.9021	High Similarity	NPC107625
0.9014	High Similarity	NPC86373
0.9014	High Similarity	NPC277426
0.9014	High Similarity	NPC66404
0.9014	High Similarity	NPC19896
0.9014	High Similarity	NPC95123
0.9014	High Similarity	NPC280404
0.9014	High Similarity	NPC210425
0.9007	High Similarity	NPC105648
0.9007	High Similarity	NPC469579
0.9007	High Similarity	NPC471733
0.9007	High Similarity	NPC82913
0.9	High Similarity	NPC472601
0.9	High Similarity	NPC168471
0.9	High Similarity	NPC472600
0.8993	High Similarity	NPC212693
0.8993	High Similarity	NPC191835
0.8993	High Similarity	NPC94248
0.8986	High Similarity	NPC146211
0.8986	High Similarity	NPC235115
0.8971	High Similarity	NPC27490
0.8966	High Similarity	NPC329933
0.8966	High Similarity	NPC198927
0.8966	High Similarity	NPC288036
0.8966	High Similarity	NPC97029
0.8966	High Similarity	NPC65589
0.8966	High Similarity	NPC158338
0.8966	High Similarity	NPC97028
0.8966	High Similarity	NPC100985
0.8963	High Similarity	NPC307732
0.8963	High Similarity	NPC84772
0.8963	High Similarity	NPC42292
0.8958	High Similarity	NPC53362
0.8958	High Similarity	NPC166583
0.8958	High Similarity	NPC14098
0.8951	High Similarity	NPC32470
0.8951	High Similarity	NPC312789
0.8951	High Similarity	NPC29577
0.8951	High Similarity	NPC472034
0.8936	High Similarity	NPC472605
0.8936	High Similarity	NPC472604
0.8936	High Similarity	NPC472603
0.8929	High Similarity	NPC105456
0.8929	High Similarity	NPC139634
0.8929	High Similarity	NPC268052
0.8929	High Similarity	NPC32360
0.8929	High Similarity	NPC92655
0.8926	High Similarity	NPC263483
0.8913	High Similarity	NPC290803
0.8904	High Similarity	NPC290954
0.8904	High Similarity	NPC470568
0.8904	High Similarity	NPC179178
0.8904	High Similarity	NPC255641
0.8904	High Similarity	NPC147735
0.8904	High Similarity	NPC294646
0.8904	High Similarity	NPC202595
0.8897	High Similarity	NPC324482
0.8897	High Similarity	NPC153417
0.8889	High Similarity	NPC473927
0.8889	High Similarity	NPC69235
0.8889	High Similarity	NPC212379
0.8889	High Similarity	NPC472033
0.8881	High Similarity	NPC305518
0.8881	High Similarity	NPC128428
0.8881	High Similarity	NPC475201
0.8873	High Similarity	NPC49108
0.8873	High Similarity	NPC322112
0.8872	High Similarity	NPC201728
0.8872	High Similarity	NPC262671
0.8865	High Similarity	NPC472366
0.8859	High Similarity	NPC4547
0.8857	High Similarity	NPC478200
0.8857	High Similarity	NPC33144
0.8857	High Similarity	NPC472602
0.8849	High Similarity	NPC118919
0.8849	High Similarity	NPC242712
0.8849	High Similarity	NPC291454
0.8849	High Similarity	NPC84699
0.8844	High Similarity	NPC478148
0.8844	High Similarity	NPC232645
0.8844	High Similarity	NPC149526
0.8844	High Similarity	NPC470569
0.8844	High Similarity	NPC474417
0.8844	High Similarity	NPC72958
0.8841	High Similarity	NPC474394
0.8841	High Similarity	NPC475645
0.8836	High Similarity	NPC77325
0.8836	High Similarity	NPC270160
0.8836	High Similarity	NPC237440
0.8836	High Similarity	NPC4423
0.8828	High Similarity	NPC210320
0.8828	High Similarity	NPC471734
0.8828	High Similarity	NPC472036
0.8824	High Similarity	NPC62219
0.8811	High Similarity	NPC310340
0.8811	High Similarity	NPC472610
0.8808	High Similarity	NPC243701
0.8808	High Similarity	NPC143050
0.8803	High Similarity	NPC149533
0.8803	High Similarity	NPC16455
0.8803	High Similarity	NPC478217
0.8803	High Similarity	NPC53649
0.8803	High Similarity	NPC158634
0.8803	High Similarity	NPC307990
0.8803	High Similarity	NPC313123
0.8803	High Similarity	NPC275734
0.8794	High Similarity	NPC247409
0.8794	High Similarity	NPC57380
0.8794	High Similarity	NPC471819
0.8794	High Similarity	NPC52358
0.8786	High Similarity	NPC71256
0.8786	High Similarity	NPC245058
0.8784	High Similarity	NPC40356
0.8784	High Similarity	NPC87708
0.8784	High Similarity	NPC154683

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 NPC165172 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	319
0.1-0.2	1044
0.2-0.3	1744
0.3-0.4	2636
0.4-0.5	1745
0.5-0.6	1076
0.6-0.7	398
0.7-0.8	152
0.8-0.85	28
0.85-0.9	5
0.9-0.95	3
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.9343	High Similarity	NPD970	Clinical (unspecified phase)
0.922	High Similarity	NPD2534	Approved
0.922	High Similarity	NPD2532	Approved
0.922	High Similarity	NPD2533	Approved
0.8705	High Similarity	NPD1607	Approved
0.8693	High Similarity	NPD6232	Discontinued
0.86	High Similarity	NPD7819	Suspended
0.8561	High Similarity	NPD1240	Approved
0.8526	High Similarity	NPD7473	Discontinued
0.8451	Intermediate Similarity	NPD1509	Clinical (unspecified phase)
0.8451	Intermediate Similarity	NPD1510	Phase 2
0.8392	Intermediate Similarity	NPD2935	Discontinued
0.8333	Intermediate Similarity	NPD5711	Approved
0.8333	Intermediate Similarity	NPD5710	Approved
0.8311	Intermediate Similarity	NPD4378	Clinical (unspecified phase)
0.8269	Intermediate Similarity	NPD6959	Discontinued
0.8264	Intermediate Similarity	NPD1551	Phase 2
0.8207	Intermediate Similarity	NPD1552	Clinical (unspecified phase)
0.8207	Intermediate Similarity	NPD1550	Clinical (unspecified phase)
0.8163	Intermediate Similarity	NPD3750	Approved
0.8151	Intermediate Similarity	NPD1549	Phase 2
0.8117	Intermediate Similarity	NPD2393	Clinical (unspecified phase)
0.8105	Intermediate Similarity	NPD7411	Suspended
0.8095	Intermediate Similarity	NPD2800	Approved
0.8095	Intermediate Similarity	NPD1243	Approved
0.8092	Intermediate Similarity	NPD3226	Approved
0.8077	Intermediate Similarity	NPD7075	Discontinued
0.8056	Intermediate Similarity	NPD6651	Approved
0.8041	Intermediate Similarity	NPD6398	Clinical (unspecified phase)
0.8041	Intermediate Similarity	NPD1878	Clinical (unspecified phase)
0.8039	Intermediate Similarity	NPD6599	Discontinued
0.8015	Intermediate Similarity	NPD4626	Approved
0.8013	Intermediate Similarity	NPD7768	Phase 2
0.8	Intermediate Similarity	NPD7096	Clinical (unspecified phase)
0.8	Intermediate Similarity	NPD1511	Approved
0.8	Intermediate Similarity	NPD7390	Discontinued
0.7986	Intermediate Similarity	NPD1283	Approved
0.7986	Intermediate Similarity	NPD230	Phase 1
0.7963	Intermediate Similarity	NPD5844	Phase 1
0.7962	Intermediate Similarity	NPD3749	Approved
0.7959	Intermediate Similarity	NPD2346	Discontinued
0.7949	Intermediate Similarity	NPD8443	Clinical (unspecified phase)
0.7947	Intermediate Similarity	NPD7410	Clinical (unspecified phase)
0.7935	Intermediate Similarity	NPD1934	Approved
0.7922	Intermediate Similarity	NPD4380	Phase 2
0.7902	Intermediate Similarity	NPD411	Approved
0.7895	Intermediate Similarity	NPD1512	Approved
0.7891	Intermediate Similarity	NPD5405	Approved
0.7891	Intermediate Similarity	NPD5404	Approved
0.7891	Intermediate Similarity	NPD5408	Approved
0.7891	Intermediate Similarity	NPD5406	Approved
0.7888	Intermediate Similarity	NPD7852	Clinical (unspecified phase)
0.7881	Intermediate Similarity	NPD6799	Approved
0.7852	Intermediate Similarity	NPD9493	Approved
0.7843	Intermediate Similarity	NPD920	Approved
0.7842	Intermediate Similarity	NPD9717	Approved
0.7823	Intermediate Similarity	NPD3748	Approved
0.7821	Intermediate Similarity	NPD6801	Discontinued
0.7815	Intermediate Similarity	NPD643	Clinical (unspecified phase)
0.7778	Intermediate Similarity	NPD6859	Clinical (unspecified phase)
0.7771	Intermediate Similarity	NPD2801	Approved
0.7771	Intermediate Similarity	NPD1465	Phase 2
0.777	Intermediate Similarity	NPD6099	Approved
0.777	Intermediate Similarity	NPD2796	Approved
0.777	Intermediate Similarity	NPD6100	Approved
0.777	Intermediate Similarity	NPD1281	Approved
0.7737	Intermediate Similarity	NPD9545	Approved
0.7733	Intermediate Similarity	NPD7421	Clinical (unspecified phase)
0.7722	Intermediate Similarity	NPD3817	Phase 2
0.7712	Intermediate Similarity	NPD642	Clinical (unspecified phase)
0.7703	Intermediate Similarity	NPD2799	Discontinued
0.7703	Intermediate Similarity	NPD651	Clinical (unspecified phase)
0.7688	Intermediate Similarity	NPD919	Approved
0.7682	Intermediate Similarity	NPD7003	Approved
0.7682	Intermediate Similarity	NPD4628	Phase 3
0.7681	Intermediate Similarity	NPD5691	Approved
0.7676	Intermediate Similarity	NPD1203	Approved
0.7673	Intermediate Similarity	NPD3882	Suspended
0.7673	Intermediate Similarity	NPD4868	Clinical (unspecified phase)
0.7671	Intermediate Similarity	NPD943	Approved
0.7655	Intermediate Similarity	NPD1699	Clinical (unspecified phase)
0.7643	Intermediate Similarity	NPD1201	Approved
0.7643	Intermediate Similarity	NPD422	Phase 1
0.7619	Intermediate Similarity	NPD447	Suspended
0.7605	Intermediate Similarity	NPD6559	Discontinued
0.7589	Intermediate Similarity	NPD1608	Approved
0.7552	Intermediate Similarity	NPD1164	Approved
0.7552	Intermediate Similarity	NPD1470	Approved
0.7545	Intermediate Similarity	NPD5953	Discontinued
0.7516	Intermediate Similarity	NPD5808	Clinical (unspecified phase)
0.7516	Intermediate Similarity	NPD4381	Clinical (unspecified phase)
0.7514	Intermediate Similarity	NPD7879	Clinical (unspecified phase)
0.75	Intermediate Similarity	NPD2654	Approved
0.7484	Intermediate Similarity	NPD37	Approved
0.7466	Intermediate Similarity	NPD4625	Phase 3
0.7465	Intermediate Similarity	NPD9269	Phase 2
0.7455	Intermediate Similarity	NPD6168	Clinical (unspecified phase)
0.7455	Intermediate Similarity	NPD6166	Phase 2
0.7455	Intermediate Similarity	NPD6167	Clinical (unspecified phase)
0.7429	Intermediate Similarity	NPD9268	Approved
0.7429	Intermediate Similarity	NPD1651	Approved
0.7425	Intermediate Similarity	NPD7286	Phase 2
0.7425	Intermediate Similarity	NPD7804	Clinical (unspecified phase)
0.7423	Intermediate Similarity	NPD5494	Approved
0.7415	Intermediate Similarity	NPD2313	Discontinued
0.7415	Intermediate Similarity	NPD3764	Approved
0.7405	Intermediate Similarity	NPD7458	Discontinued
0.7389	Intermediate Similarity	NPD6980	Clinical (unspecified phase)
0.7381	Intermediate Similarity	NPD7074	Phase 3
0.7379	Intermediate Similarity	NPD6917	Clinical (unspecified phase)
0.7376	Intermediate Similarity	NPD17	Approved
0.7376	Intermediate Similarity	NPD1778	Approved
0.7372	Intermediate Similarity	NPD7004	Clinical (unspecified phase)
0.7368	Intermediate Similarity	NPD2344	Approved
0.7365	Intermediate Similarity	NPD3818	Discontinued
0.7362	Intermediate Similarity	NPD6234	Discontinued
0.7351	Intermediate Similarity	NPD4308	Phase 3
0.7346	Intermediate Similarity	NPD4967	Phase 2
0.7346	Intermediate Similarity	NPD4966	Approved
0.7346	Intermediate Similarity	NPD4965	Approved
0.7333	Intermediate Similarity	NPD7229	Phase 3
0.7321	Intermediate Similarity	NPD7054	Approved
0.7315	Intermediate Similarity	NPD2979	Phase 3
0.7299	Intermediate Similarity	NPD8397	Clinical (unspecified phase)
0.7297	Intermediate Similarity	NPD1296	Phase 2
0.7292	Intermediate Similarity	NPD4749	Approved
0.7284	Intermediate Similarity	NPD5402	Approved
0.7284	Intermediate Similarity	NPD4288	Approved
0.7279	Intermediate Similarity	NPD6832	Phase 2
0.7278	Intermediate Similarity	NPD7472	Approved
0.7278	Intermediate Similarity	NPD5403	Approved
0.7273	Intermediate Similarity	NPD1247	Approved
0.7267	Intermediate Similarity	NPD1899	Clinical (unspecified phase)
0.7262	Intermediate Similarity	NPD7177	Discontinued
0.7261	Intermediate Similarity	NPD5401	Approved
0.726	Intermediate Similarity	NPD2798	Approved
0.726	Intermediate Similarity	NPD1019	Discontinued
0.7259	Intermediate Similarity	NPD9266	Approved
0.7259	Intermediate Similarity	NPD74	Approved
0.7251	Intermediate Similarity	NPD4338	Clinical (unspecified phase)
0.7251	Intermediate Similarity	NPD4419	Clinical (unspecified phase)
0.7235	Intermediate Similarity	NPD6797	Phase 2
0.7222	Intermediate Similarity	NPD3972	Approved
0.7214	Intermediate Similarity	NPD405	Clinical (unspecified phase)
0.7211	Intermediate Similarity	NPD9494	Approved
0.7209	Intermediate Similarity	NPD8313	Approved
0.7209	Intermediate Similarity	NPD8312	Approved
0.72	Intermediate Similarity	NPD4060	Phase 1
0.7197	Intermediate Similarity	NPD6143	Clinical (unspecified phase)
0.7193	Intermediate Similarity	NPD7251	Discontinued
0.7192	Intermediate Similarity	NPD2797	Approved
0.719	Intermediate Similarity	NPD2438	Suspended
0.7189	Intermediate Similarity	NPD8151	Discontinued
0.7185	Intermediate Similarity	NPD9264	Approved
0.7185	Intermediate Similarity	NPD9263	Approved
0.7185	Intermediate Similarity	NPD9267	Approved
0.7185	Intermediate Similarity	NPD9265	Clinical (unspecified phase)
0.7181	Intermediate Similarity	NPD6410	Clinical (unspecified phase)
0.7181	Intermediate Similarity	NPD4907	Clinical (unspecified phase)
0.7181	Intermediate Similarity	NPD3268	Approved
0.7179	Intermediate Similarity	NPD2309	Approved
0.7169	Intermediate Similarity	NPD7199	Phase 2
0.7153	Intermediate Similarity	NPD1610	Phase 2
0.7152	Intermediate Similarity	NPD5124	Phase 1
0.7152	Intermediate Similarity	NPD7422	Clinical (unspecified phase)
0.7152	Intermediate Similarity	NPD5123	Clinical (unspecified phase)
0.7151	Intermediate Similarity	NPD7808	Phase 3
0.7143	Intermediate Similarity	NPD1471	Phase 3
0.7135	Intermediate Similarity	NPD7993	Clinical (unspecified phase)
0.7124	Intermediate Similarity	NPD7033	Discontinued
0.7107	Intermediate Similarity	NPD6273	Approved
0.7104	Intermediate Similarity	NPD7435	Discontinued
0.7086	Intermediate Similarity	NPD4307	Phase 2
0.7086	Intermediate Similarity	NPD8150	Discontinued
0.7083	Intermediate Similarity	NPD3926	Phase 2
0.7083	Intermediate Similarity	NPD7184	Clinical (unspecified phase)
0.7078	Intermediate Similarity	NPD4476	Approved
0.7078	Intermediate Similarity	NPD4477	Approved
0.7078	Intermediate Similarity	NPD2531	Phase 2
0.7063	Intermediate Similarity	NPD4196	Clinical (unspecified phase)
0.7059	Intermediate Similarity	NPD7228	Approved
0.7055	Intermediate Similarity	NPD3600	Clinical (unspecified phase)
0.7047	Intermediate Similarity	NPD4908	Phase 1
0.7034	Intermediate Similarity	NPD1611	Approved
0.7033	Intermediate Similarity	NPD6780	Approved
0.7033	Intermediate Similarity	NPD6776	Approved
0.7033	Intermediate Similarity	NPD6777	Approved
0.7033	Intermediate Similarity	NPD6781	Approved
0.7033	Intermediate Similarity	NPD6778	Approved
0.7033	Intermediate Similarity	NPD6779	Approved
0.7033	Intermediate Similarity	NPD6782	Approved
0.7032	Intermediate Similarity	NPD6003	Clinical (unspecified phase)
0.7032	Intermediate Similarity	NPD6002	Phase 3
0.7032	Intermediate Similarity	NPD6006	Clinical (unspecified phase)
0.7032	Intermediate Similarity	NPD6004	Phase 3
0.7032	Intermediate Similarity	NPD6005	Phase 3
0.7007	Intermediate Similarity	NPD3225	Approved
0.7007	Intermediate Similarity	NPD1876	Approved
0.7007	Intermediate Similarity	NPD6696	Suspended
0.7006	Intermediate Similarity	NPD4287	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