NPASS Compound

Structure

Physi-Chem Properties

Molecular Weight:	194.06
Volume:	194.938
LogP:	2.383
LogD:	4.194
LogS:	-3.888
# Rotatable Bonds:	4
TPSA:	52.6
# H-Bond Aceptor:	4
# H-Bond Donor:	0
# Rings:	1
# Heavy Atoms:	4

MedChem Properties

QED Drug-Likeness Score:	0.665
Synthetic Accessibility Score:	1.34
Fsp3:	0.2
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Accepted
GSK Rule:	Accepted
BMS Rule:	0
Golden Triangle Rule:	Rejected
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-4.488
MDCK Permeability:	4.291050208848901e-05
Pgp-inhibitor:	0.021
Pgp-substrate:	0.0
Human Intestinal Absorption (HIA):	0.005
20% Bioavailability (F20%):	0.184
30% Bioavailability (F30%):	0.982

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.804
Plasma Protein Binding (PPB):	79.46733856201172%
Volume Distribution (VD):	0.87
Pgp-substrate:	11.969403266906738%

ADMET: Metabolism

CYP1A2-inhibitor:	0.977
CYP1A2-substrate:	0.924
CYP2C19-inhibitor:	0.885
CYP2C19-substrate:	0.159
CYP2C9-inhibitor:	0.383
CYP2C9-substrate:	0.81
CYP2D6-inhibitor:	0.071
CYP2D6-substrate:	0.4
CYP3A4-inhibitor:	0.065
CYP3A4-substrate:	0.187

ADMET: Excretion

Clearance (CL):	10.545
Half-life (T1/2):	0.88

ADMET: Toxicity

hERG Blockers:	0.106
Human Hepatotoxicity (H-HT):	0.032
Drug-inuced Liver Injury (DILI):	0.769
AMES Toxicity:	0.007
Rat Oral Acute Toxicity:	0.008
Maximum Recommended Daily Dose:	0.011
Skin Sensitization:	0.243
Carcinogencity:	0.024
Eye Corrosion:	0.005
Eye Irritation:	0.98
Respiratory Toxicity:	0.041

Download Data

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

Natural Product: NPC203925

Natural Product ID:	NPC203925
*Common Name:**	Dimethyl Benzene-1,4-Dicarboxylate
IUPAC Name:	dimethyl benzene-1,4-dicarboxylate
Synonyms:
Standard InCHIKey:	WOZVHXUHUFLZGK-UHFFFAOYSA-N
Standard InCHI:	InChI=1S/C10H10O4/c1-13-9(11)7-3-5-8(6-4-7)10(12)14-2/h3-6H,1-2H3
SMILES:	COC(=O)c1ccc(cc1)C(=O)OC
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL1870757
PubChem CID:	8441
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0002448] Benzenoids [CHEMONTID:0002279] Benzene and substituted derivatives [CHEMONTID:0000176] Benzoic acids and derivatives [CHEMONTID:0001105] Phthalic acid and derivatives [CHEMONTID:0004009] Phthalate esters [CHEMONTID:0004012] p-Phthalate esters

*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
NPO1104	Selinum carvifolia	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO15603	Aspergillus petrakii	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO3607	Derris obtusa	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO1740	Gomphrena celosioides	Species	Amaranthaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO2072	Fomes juniperinus	Species	Coriolaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO1667	Cylindropuntia echinocarpus	Species	Cactaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO3818	Parkinsonia aculeata	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO5226	Acrostalagmus cinnabarinus	Species	Plectosphaerellaceae	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
Potency	16

Activity Type	# Activity
Individual Protein	2
Others	14

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT46	Individual Protein	Thyroid hormone receptor beta-1	Homo sapiens	Potency	n.a.	2511.9	nM	PMID[531472]
NPT610	Others	Molecular identity unknown		Potency	n.a.	70794.6	nM	PMID[531472]
NPT2	Others	Unspecified		Potency	n.a.	197.6	nM	PubChem BioAssay data set
NPT2	Others	Unspecified		Potency	n.a.	77977.4	nM	PubChem BioAssay data set
NPT2	Others	Unspecified		Potency	n.a.	2487.5	nM	PubChem BioAssay data set
NPT2	Others	Unspecified		Potency	n.a.	19758.8	nM	PubChem BioAssay data set
NPT2	Others	Unspecified		Potency	n.a.	24874.9	nM	PubChem BioAssay data set
NPT2	Others	Unspecified		Potency	n.a.	61644.8	nM	PubChem BioAssay data set
NPT74	Individual Protein	Proto-oncogene c-JUN	Homo sapiens	Potency	n.a.	7866.1	nM	PubChem BioAssay data set
NPT2	Others	Unspecified		Potency	n.a.	15695	nM	PubChem BioAssay data set
NPT2	Others	Unspecified		Potency	n.a.	12467	nM	PubChem BioAssay data set
NPT2	Others	Unspecified		Potency	n.a.	3131.6	nM	PubChem BioAssay data set
NPT2	Others	Unspecified		Potency	n.a.	3104.3	nM	PubChem BioAssay data set
NPT2	Others	Unspecified		Potency	n.a.	13866.6	nM	PubChem BioAssay data set
NPT2	Others	Unspecified		Potency	n.a.	17457	nM	PubChem BioAssay data set
NPT2	Others	Unspecified		Potency	n.a.	1958.7	nM	PubChem BioAssay data set

☑ 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 NPC203925 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	247
0.1-0.2	1657
0.2-0.3	4033
0.3-0.4	10290
0.4-0.5	10809
0.5-0.6	11272
0.6-0.7	3869
0.7-0.8	429
0.8-0.85	46
0.85-0.9	29
0.9-0.95	14
0.95-1	2

Similarity Score	Similarity Level	Natural Product ID
0.9681	High Similarity	NPC70624
0.9579	High Similarity	NPC188895
0.9565	High Similarity	NPC130398
0.9362	High Similarity	NPC276775
0.9362	High Similarity	NPC249912
0.9362	High Similarity	NPC92754
0.9263	High Similarity	NPC78701
0.9263	High Similarity	NPC225060
0.9263	High Similarity	NPC35448
0.9167	High Similarity	NPC146351
0.9082	High Similarity	NPC474365
0.9082	High Similarity	NPC301943
0.899	High Similarity	NPC31786
0.8969	High Similarity	NPC118343
0.8969	High Similarity	NPC325497
0.8958	High Similarity	NPC253423
0.8878	High Similarity	NPC42211
0.8854	High Similarity	NPC61944
0.8812	High Similarity	NPC119271
0.8776	High Similarity	NPC217621
0.8725	High Similarity	NPC56493
0.8713	High Similarity	NPC269457
0.8696	High Similarity	NPC318107
0.8646	High Similarity	NPC261181
0.8641	High Similarity	NPC469636
0.8641	High Similarity	NPC474364
0.8641	High Similarity	NPC10251
0.8641	High Similarity	NPC85493
0.8641	High Similarity	NPC17417
0.8617	High Similarity	NPC173443
0.86	High Similarity	NPC25458
0.86	High Similarity	NPC304873
0.8558	High Similarity	NPC251854
0.8558	High Similarity	NPC174099
0.8558	High Similarity	NPC93084
0.8558	High Similarity	NPC196246
0.8558	High Similarity	NPC214067
0.8529	High Similarity	NPC209632
0.8515	High Similarity	NPC89886
0.8515	High Similarity	NPC60679
0.8491	Intermediate Similarity	NPC128368
0.8476	Intermediate Similarity	NPC260818
0.8476	Intermediate Similarity	NPC305912
0.8476	Intermediate Similarity	NPC1082
0.8462	Intermediate Similarity	NPC265407
0.8462	Intermediate Similarity	NPC83628
0.8447	Intermediate Similarity	NPC37622
0.8447	Intermediate Similarity	NPC30594
0.8431	Intermediate Similarity	NPC114594
0.8416	Intermediate Similarity	NPC45613
0.8411	Intermediate Similarity	NPC307651
0.8404	Intermediate Similarity	NPC89377
0.8396	Intermediate Similarity	NPC82899
0.8396	Intermediate Similarity	NPC321852
0.8396	Intermediate Similarity	NPC270699
0.835	Intermediate Similarity	NPC105899
0.8333	Intermediate Similarity	NPC62765
0.8318	Intermediate Similarity	NPC161611
0.8302	Intermediate Similarity	NPC476003
0.8302	Intermediate Similarity	NPC474157
0.8302	Intermediate Similarity	NPC210089
0.83	Intermediate Similarity	NPC229242
0.8286	Intermediate Similarity	NPC269023
0.8286	Intermediate Similarity	NPC99846
0.8257	Intermediate Similarity	NPC149691
0.8241	Intermediate Similarity	NPC153053
0.8241	Intermediate Similarity	NPC474363
0.8229	Intermediate Similarity	NPC220893
0.8224	Intermediate Similarity	NPC474314
0.8191	Intermediate Similarity	NPC58616
0.819	Intermediate Similarity	NPC249811
0.8172	Intermediate Similarity	NPC288903
0.8165	Intermediate Similarity	NPC210092
0.8165	Intermediate Similarity	NPC81808
0.8148	Intermediate Similarity	NPC474176
0.8148	Intermediate Similarity	NPC272524
0.8131	Intermediate Similarity	NPC167504
0.8073	Intermediate Similarity	NPC308744
0.8065	Intermediate Similarity	NPC106313
0.8061	Intermediate Similarity	NPC119631
0.8058	Intermediate Similarity	NPC284477
0.8056	Intermediate Similarity	NPC158282
0.8056	Intermediate Similarity	NPC79496
0.8039	Intermediate Similarity	NPC228435
0.802	Intermediate Similarity	NPC270654
0.8	Intermediate Similarity	NPC474685
0.8	Intermediate Similarity	NPC294134
0.8	Intermediate Similarity	NPC472703
0.7981	Intermediate Similarity	NPC255676
0.7961	Intermediate Similarity	NPC282895
0.7961	Intermediate Similarity	NPC473325
0.7946	Intermediate Similarity	NPC228318
0.7946	Intermediate Similarity	NPC240664
0.7944	Intermediate Similarity	NPC318327
0.7938	Intermediate Similarity	NPC304760
0.7931	Intermediate Similarity	NPC472704
0.7928	Intermediate Similarity	NPC220540
0.7928	Intermediate Similarity	NPC188907
0.7895	Intermediate Similarity	NPC473243
0.789	Intermediate Similarity	NPC66208
0.7857	Intermediate Similarity	NPC128825
0.7857	Intermediate Similarity	NPC131192
0.7838	Intermediate Similarity	NPC474095
0.7838	Intermediate Similarity	NPC306740
0.7826	Intermediate Similarity	NPC50872
0.7818	Intermediate Similarity	NPC13784
0.781	Intermediate Similarity	NPC234305
0.7798	Intermediate Similarity	NPC243355
0.7788	Intermediate Similarity	NPC217423
0.7788	Intermediate Similarity	NPC469574
0.7788	Intermediate Similarity	NPC45104
0.7768	Intermediate Similarity	NPC100353
0.7768	Intermediate Similarity	NPC135730
0.7757	Intermediate Similarity	NPC1065
0.7748	Intermediate Similarity	NPC196075
0.7748	Intermediate Similarity	NPC237366
0.7748	Intermediate Similarity	NPC477411
0.7739	Intermediate Similarity	NPC230951
0.7736	Intermediate Similarity	NPC85977
0.7731	Intermediate Similarity	NPC472706
0.7727	Intermediate Similarity	NPC212415
0.7727	Intermediate Similarity	NPC54626
0.7727	Intermediate Similarity	NPC23332
0.7719	Intermediate Similarity	NPC94298
0.7719	Intermediate Similarity	NPC27633
0.7719	Intermediate Similarity	NPC171023
0.7719	Intermediate Similarity	NPC94637
0.7717	Intermediate Similarity	NPC3672
0.7717	Intermediate Similarity	NPC287790
0.77	Intermediate Similarity	NPC110704
0.7679	Intermediate Similarity	NPC186933
0.7679	Intermediate Similarity	NPC228936
0.7667	Intermediate Similarity	NPC472707
0.7652	Intermediate Similarity	NPC61779
0.7652	Intermediate Similarity	NPC90522
0.7652	Intermediate Similarity	NPC472708
0.7652	Intermediate Similarity	NPC328459
0.7636	Intermediate Similarity	NPC183648
0.7627	Intermediate Similarity	NPC228739
0.7615	Intermediate Similarity	NPC281604
0.7611	Intermediate Similarity	NPC226093
0.7604	Intermediate Similarity	NPC285773
0.76	Intermediate Similarity	NPC240108
0.76	Intermediate Similarity	NPC274455
0.76	Intermediate Similarity	NPC213156
0.76	Intermediate Similarity	NPC70940
0.76	Intermediate Similarity	NPC86670
0.7589	Intermediate Similarity	NPC53953
0.7586	Intermediate Similarity	NPC72977
0.7579	Intermediate Similarity	NPC100039
0.7576	Intermediate Similarity	NPC329064
0.757	Intermediate Similarity	NPC269644
0.7568	Intermediate Similarity	NPC57879
0.7563	Intermediate Similarity	NPC125053
0.7563	Intermediate Similarity	NPC295664
0.7563	Intermediate Similarity	NPC246166
0.7553	Intermediate Similarity	NPC167577
0.7553	Intermediate Similarity	NPC78517
0.7545	Intermediate Similarity	NPC234639
0.7544	Intermediate Similarity	NPC158157
0.7544	Intermediate Similarity	NPC470860
0.7542	Intermediate Similarity	NPC223351
0.7524	Intermediate Similarity	NPC98911
0.7524	Intermediate Similarity	NPC472318
0.7523	Intermediate Similarity	NPC470391
0.7522	Intermediate Similarity	NPC476357
0.7522	Intermediate Similarity	NPC221275
0.7521	Intermediate Similarity	NPC144547
0.75	Intermediate Similarity	NPC9822
0.75	Intermediate Similarity	NPC323103
0.75	Intermediate Similarity	NPC275576
0.75	Intermediate Similarity	NPC204784
0.75	Intermediate Similarity	NPC470765
0.75	Intermediate Similarity	NPC476599
0.75	Intermediate Similarity	NPC17693
0.7479	Intermediate Similarity	NPC85511
0.7478	Intermediate Similarity	NPC160199
0.7477	Intermediate Similarity	NPC160382
0.7477	Intermediate Similarity	NPC474057
0.7477	Intermediate Similarity	NPC291426
0.7477	Intermediate Similarity	NPC329556
0.7476	Intermediate Similarity	NPC5472
0.7475	Intermediate Similarity	NPC96625
0.7475	Intermediate Similarity	NPC322387
0.7474	Intermediate Similarity	NPC121800
0.7458	Intermediate Similarity	NPC26285
0.7451	Intermediate Similarity	NPC77273
0.7447	Intermediate Similarity	NPC176228
0.7438	Intermediate Similarity	NPC51292
0.7438	Intermediate Similarity	NPC473220
0.7438	Intermediate Similarity	NPC470753
0.7438	Intermediate Similarity	NPC154275
0.7438	Intermediate Similarity	NPC169913
0.7436	Intermediate Similarity	NPC233282
0.7436	Intermediate Similarity	NPC232958
0.7436	Intermediate Similarity	NPC289432
0.7436	Intermediate Similarity	NPC988
0.7434	Intermediate Similarity	NPC109241
0.7431	Intermediate Similarity	NPC474376
0.7431	Intermediate Similarity	NPC472315

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 NPC203925 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	233
0.1-0.2	957
0.2-0.3	1308
0.3-0.4	2909
0.4-0.5	2309
0.5-0.6	1077
0.6-0.7	278
0.7-0.8	69
0.8-0.85	5
0.85-0.9	5
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.899	High Similarity	NPD164	Approved
0.8969	High Similarity	NPD1238	Approved
0.8696	High Similarity	NPD9257	Approved
0.8696	High Similarity	NPD9259	Approved
0.8646	High Similarity	NPD1202	Approved
0.8641	High Similarity	NPD2182	Approved
0.8333	Intermediate Similarity	NPD9256	Approved
0.8333	Intermediate Similarity	NPD9258	Approved
0.8302	Intermediate Similarity	NPD2181	Clinical (unspecified phase)
0.807	Intermediate Similarity	NPD6287	Discontinued
0.8	Intermediate Similarity	NPD9260	Approved
0.7857	Intermediate Similarity	NPD9493	Approved
0.7835	Intermediate Similarity	NPD1087	Approved
0.7778	Intermediate Similarity	NPD6831	Clinical (unspecified phase)
0.7742	Intermediate Similarity	NPD9490	Approved
0.7727	Intermediate Similarity	NPD1609	Clinical (unspecified phase)
0.7727	Intermediate Similarity	NPD9508	Approved
0.7719	Intermediate Similarity	NPD9545	Approved
0.7679	Intermediate Similarity	NPD690	Clinical (unspecified phase)
0.7679	Intermediate Similarity	NPD5951	Approved
0.7677	Intermediate Similarity	NPD800	Approved
0.7634	Intermediate Similarity	NPD225	Approved
0.7634	Intermediate Similarity	NPD227	Approved
0.7604	Intermediate Similarity	NPD9491	Approved
0.76	Intermediate Similarity	NPD1086	Approved
0.76	Intermediate Similarity	NPD1089	Approved
0.76	Intermediate Similarity	NPD1090	Approved
0.7573	Intermediate Similarity	NPD1989	Approved
0.7541	Intermediate Similarity	NPD5952	Clinical (unspecified phase)
0.7524	Intermediate Similarity	NPD2066	Phase 3
0.7477	Intermediate Similarity	NPD1929	Approved
0.7477	Intermediate Similarity	NPD1930	Approved
0.7477	Intermediate Similarity	NPD1931	Clinical (unspecified phase)
0.7477	Intermediate Similarity	NPD9261	Approved
0.7458	Intermediate Similarity	NPD518	Clinical (unspecified phase)
0.7451	Intermediate Similarity	NPD1088	Approved
0.7429	Intermediate Similarity	NPD9495	Approved
0.7407	Intermediate Similarity	NPD1237	Approved
0.7398	Intermediate Similarity	NPD7008	Discontinued
0.7396	Intermediate Similarity	NPD226	Approved
0.7395	Intermediate Similarity	NPD9717	Approved
0.7387	Intermediate Similarity	NPD2067	Discontinued
0.7383	Intermediate Similarity	NPD1932	Approved
0.7379	Intermediate Similarity	NPD1563	Approved
0.7353	Intermediate Similarity	NPD1239	Approved
0.7345	Intermediate Similarity	NPD5277	Phase 2
0.7308	Intermediate Similarity	NPD1693	Approved
0.7295	Intermediate Similarity	NPD1019	Discontinued
0.7288	Intermediate Similarity	NPD3412	Clinical (unspecified phase)
0.7288	Intermediate Similarity	NPD7163	Clinical (unspecified phase)
0.7288	Intermediate Similarity	NPD1362	Clinical (unspecified phase)
0.7281	Intermediate Similarity	NPD1241	Discontinued
0.7273	Intermediate Similarity	NPD2199	Approved
0.7273	Intermediate Similarity	NPD2198	Approved
0.725	Intermediate Similarity	NPD3972	Approved
0.7232	Intermediate Similarity	NPD1317	Discontinued
0.7227	Intermediate Similarity	NPD1889	Phase 1
0.7222	Intermediate Similarity	NPD4307	Phase 2
0.7213	Intermediate Similarity	NPD552	Approved
0.7213	Intermediate Similarity	NPD9567	Approved
0.7213	Intermediate Similarity	NPD553	Approved
0.7207	Intermediate Similarity	NPD1358	Approved
0.7207	Intermediate Similarity	NPD9264	Approved
0.7207	Intermediate Similarity	NPD9267	Approved
0.7207	Intermediate Similarity	NPD9263	Approved
0.7207	Intermediate Similarity	NPD9265	Clinical (unspecified phase)
0.72	Intermediate Similarity	NPD411	Approved
0.719	Intermediate Similarity	NPD182	Clinical (unspecified phase)
0.7177	Intermediate Similarity	NPD6832	Phase 2
0.717	Intermediate Similarity	NPD1566	Phase 3
0.717	Intermediate Similarity	NPD1565	Approved
0.717	Intermediate Similarity	NPD1564	Approved
0.7167	Intermediate Similarity	NPD1281	Approved
0.7143	Intermediate Similarity	NPD9266	Approved
0.7143	Intermediate Similarity	NPD74	Approved
0.7143	Intermediate Similarity	NPD2329	Discontinued
0.7129	Intermediate Similarity	NPD1282	Approved
0.7117	Intermediate Similarity	NPD3134	Approved
0.7109	Intermediate Similarity	NPD3528	Clinical (unspecified phase)
0.7091	Intermediate Similarity	NPD5909	Discontinued
0.7087	Intermediate Similarity	NPD3673	Approved
0.7087	Intermediate Similarity	NPD3672	Approved
0.7073	Intermediate Similarity	NPD1203	Approved
0.7048	Intermediate Similarity	NPD5122	Clinical (unspecified phase)
0.7034	Intermediate Similarity	NPD2347	Approved
0.7031	Intermediate Similarity	NPD1899	Clinical (unspecified phase)
0.7009	Intermediate Similarity	NPD4198	Discontinued
0.7	Intermediate Similarity	NPD6647	Phase 2
0.7	Intermediate Similarity	NPD1104	Approved
0.7	Intermediate Similarity	NPD4308	Phase 3
0.6992	Remote Similarity	NPD1876	Approved
0.6992	Remote Similarity	NPD1283	Approved
0.6992	Remote Similarity	NPD1888	Phase 1
0.6981	Remote Similarity	NPD688	Clinical (unspecified phase)
0.6961	Remote Similarity	NPD650	Approved
0.6947	Remote Similarity	NPD1551	Phase 2
0.6947	Remote Similarity	NPD9716	Approved
0.6929	Remote Similarity	NPD2313	Discontinued
0.6929	Remote Similarity	NPD3764	Approved
0.6923	Remote Similarity	NPD2629	Approved
0.6923	Remote Similarity	NPD9281	Approved
0.6899	Remote Similarity	NPD230	Phase 1
0.6899	Remote Similarity	NPD1933	Approved
0.6899	Remote Similarity	NPD447	Suspended
0.6894	Remote Similarity	NPD2346	Discontinued
0.6894	Remote Similarity	NPD7702	Clinical (unspecified phase)
0.6885	Remote Similarity	NPD1547	Clinical (unspecified phase)
0.688	Remote Similarity	NPD2798	Approved
0.6875	Remote Similarity	NPD9697	Approved
0.687	Remote Similarity	NPD4141	Clinical (unspecified phase)
0.6869	Remote Similarity	NPD942	Approved
0.6866	Remote Similarity	NPD4628	Phase 3
0.686	Remote Similarity	NPD1778	Approved
0.686	Remote Similarity	NPD17	Approved
0.6827	Remote Similarity	NPD5347	Phase 2
0.6827	Remote Similarity	NPD5346	Phase 2
0.6822	Remote Similarity	NPD3373	Approved
0.6818	Remote Similarity	NPD2935	Discontinued
0.681	Remote Similarity	NPD969	Suspended
0.6803	Remote Similarity	NPD7457	Clinical (unspecified phase)
0.6797	Remote Similarity	NPD9471	Clinical (unspecified phase)
0.6796	Remote Similarity	NPD4793	Discontinued
0.6794	Remote Similarity	NPD2569	Approved
0.6794	Remote Similarity	NPD2567	Approved
0.6789	Remote Similarity	NPD5926	Approved
0.6777	Remote Similarity	NPD5691	Approved
0.6777	Remote Similarity	NPD1651	Approved
0.6746	Remote Similarity	NPD6007	Clinical (unspecified phase)
0.6744	Remote Similarity	NPD7713	Phase 3
0.6742	Remote Similarity	NPD2799	Discontinued
0.6741	Remote Similarity	NPD7003	Approved
0.6727	Remote Similarity	NPD7798	Approved
0.6721	Remote Similarity	NPD4626	Approved
0.6719	Remote Similarity	NPD6966	Discovery
0.6698	Remote Similarity	NPD7609	Phase 3
0.6694	Remote Similarity	NPD1608	Approved
0.6694	Remote Similarity	NPD1894	Discontinued
0.6693	Remote Similarity	NPD9494	Approved
0.6692	Remote Similarity	NPD2979	Phase 3
0.6667	Remote Similarity	NPD3266	Approved
0.6667	Remote Similarity	NPD3267	Approved
0.6667	Remote Similarity	NPD2670	Approved
0.6667	Remote Similarity	NPD689	Discontinued
0.6642	Remote Similarity	NPD7236	Approved
0.6642	Remote Similarity	NPD2343	Clinical (unspecified phase)
0.6639	Remote Similarity	NPD1245	Approved
0.6639	Remote Similarity	NPD5585	Approved
0.6639	Remote Similarity	NPD1246	Approved
0.6638	Remote Similarity	NPD5235	Approved
0.6638	Remote Similarity	NPD5236	Approved
0.6638	Remote Similarity	NPD5240	Approved
0.6638	Remote Similarity	NPD5239	Approved
0.6638	Remote Similarity	NPD5237	Approved
0.6636	Remote Similarity	NPD7631	Approved
0.6635	Remote Similarity	NPD506	Clinical (unspecified phase)
0.6633	Remote Similarity	NPD9294	Approved
0.6618	Remote Similarity	NPD1878	Clinical (unspecified phase)
0.6617	Remote Similarity	NPD3748	Approved
0.6617	Remote Similarity	NPD3170	Approved
0.6617	Remote Similarity	NPD1110	Approved
0.6617	Remote Similarity	NPD1109	Approved
0.6614	Remote Similarity	NPD6085	Phase 2
0.6614	Remote Similarity	NPD5740	Clinical (unspecified phase)
0.6612	Remote Similarity	NPD5536	Phase 2
0.661	Remote Similarity	NPD1279	Clinical (unspecified phase)
0.6591	Remote Similarity	NPD1607	Approved
0.6591	Remote Similarity	NPD1654	Clinical (unspecified phase)
0.6589	Remote Similarity	NPD6039	Approved
0.6587	Remote Similarity	NPD5667	Approved
0.6581	Remote Similarity	NPD2201	Approved
0.656	Remote Similarity	NPD1481	Phase 2
0.656	Remote Similarity	NPD6637	Approved
0.6545	Remote Similarity	NPD3495	Discontinued
0.6544	Remote Similarity	NPD7421	Clinical (unspecified phase)
0.6535	Remote Similarity	NPD2797	Approved
0.6535	Remote Similarity	NPD1164	Approved
0.6532	Remote Similarity	NPD3496	Discontinued
0.6532	Remote Similarity	NPD3847	Discontinued
0.6529	Remote Similarity	NPD694	Clinical (unspecified phase)
0.6529	Remote Similarity	NPD405	Clinical (unspecified phase)
0.6525	Remote Similarity	NPD7239	Suspended
0.6519	Remote Similarity	NPD2353	Approved
0.6519	Remote Similarity	NPD2355	Clinical (unspecified phase)
0.6504	Remote Similarity	NPD9268	Approved
0.6496	Remote Similarity	NPD4233	Approved
0.6496	Remote Similarity	NPD1752	Approved
0.6496	Remote Similarity	NPD1756	Approved
0.6496	Remote Similarity	NPD4234	Approved
0.6489	Remote Similarity	NPD520	Approved
0.648	Remote Similarity	NPD1535	Discovery
0.6479	Remote Similarity	NPD6591	Clinical (unspecified phase)
0.6479	Remote Similarity	NPD7458	Discontinued
0.6471	Remote Similarity	NPD970	Clinical (unspecified phase)
0.6471	Remote Similarity	NPD5535	Approved
0.6471	Remote Similarity	NPD6858	Approved
0.6471	Remote Similarity	NPD7094	Approved
0.6471	Remote Similarity	NPD6414	Clinical (unspecified phase)
0.6452	Remote Similarity	NPD9272	Approved
0.6452	Remote Similarity	NPD5305	Approved
0.6452	Remote Similarity	NPD2345	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