NPASS Compound

Structure

Physi-Chem Properties

Molecular Weight:	410.1
Volume:	404.72
LogP:	3.19
LogD:	2.031
LogS:	-4.114
# Rotatable Bonds:	6
TPSA:	133.52
# H-Bond Aceptor:	8
# H-Bond Donor:	4
# Rings:	3
# Heavy Atoms:	8

MedChem Properties

QED Drug-Likeness Score:	0.291
Synthetic Accessibility Score:	2.497
Fsp3:	0.091
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Accepted
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:	-5.15
MDCK Permeability:	1.5636496755178086e-05
Pgp-inhibitor:	0.062
Pgp-substrate:	0.004
Human Intestinal Absorption (HIA):	0.011
20% Bioavailability (F20%):	0.018
30% Bioavailability (F30%):	0.008

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.013
Plasma Protein Binding (PPB):	99.29595184326172%
Volume Distribution (VD):	0.462
Pgp-substrate:	2.1271371841430664%

ADMET: Metabolism

CYP1A2-inhibitor:	0.862
CYP1A2-substrate:	0.042
CYP2C19-inhibitor:	0.863
CYP2C19-substrate:	0.047
CYP2C9-inhibitor:	0.744
CYP2C9-substrate:	0.9
CYP2D6-inhibitor:	0.014
CYP2D6-substrate:	0.274
CYP3A4-inhibitor:	0.227
CYP3A4-substrate:	0.213

ADMET: Excretion

Clearance (CL):	0.872
Half-life (T1/2):	0.894

ADMET: Toxicity

hERG Blockers:	0.003
Human Hepatotoxicity (H-HT):	0.013
Drug-inuced Liver Injury (DILI):	0.949
AMES Toxicity:	0.148
Rat Oral Acute Toxicity:	0.729
Maximum Recommended Daily Dose:	0.04
Skin Sensitization:	0.247
Carcinogencity:	0.108
Eye Corrosion:	0.003
Eye Irritation:	0.771
Respiratory Toxicity:	0.112

Download Data

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

Natural Product: NPC275104

Natural Product ID:	NPC275104
*Common Name:**	Bis(4-Hydroxybenzyl)Sulfide
IUPAC Name:	4-[(4-hydroxyphenyl)methylsulfanylmethyl]phenol
Synonyms:
Standard InCHIKey:	OEISQDWSEZCYNH-UHFFFAOYSA-N
Standard InCHI:	InChI=1S/C14H14O2S/c15-13-5-1-11(2-6-13)9-17-10-12-3-7-14(16)8-4-12/h1-8,15-16H,9-10H2
SMILES:	c1cc(ccc1CSCc1ccc(cc1)O)O
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL224380
PubChem CID:	23651847
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0002448] Benzenoids [CHEMONTID:0000134] Phenols [CHEMONTID:0004646] 1-hydroxy-2-unsubstituted benzenoids

*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
NPO22309	Gastrodia elata	Species	Orchidaceae	Eukaryota	n.a.	tuber	n.a.	PMID[15180301]
NPO22309	Gastrodia elata	Species	Orchidaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[17381154]
NPO22472	Pleuropterus ciliinervis	Species	Polygonaceae	Eukaryota	n.a.	root	n.a.	PMID[17851433]
NPO22309	Gastrodia elata	Species	Orchidaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[25843525]
NPO22472	Pleuropterus ciliinervis	Species	Polygonaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO22309	Gastrodia elata	Species	Orchidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO22472	Pleuropterus ciliinervis	Species	Polygonaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO22309	Gastrodia elata	Species	Orchidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO22309	Gastrodia elata	Species	Orchidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO22309	Gastrodia elata	Species	Orchidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO22309	Gastrodia elata	Species	Orchidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO22472	Pleuropterus ciliinervis	Species	Polygonaceae	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
EC50	1
IC50	1
Ki	1

Activity Type	# Activity
Cell Line	1
Individual Protein	2

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT1316	Individual Protein	Adenosine A2a receptor	Rattus norvegicus	Ki	=	24100.0	nM	PMID[569759]
NPT1316	Individual Protein	Adenosine A2a receptor	Rattus norvegicus	IC50	=	42900.0	nM	PMID[569759]
NPT681	Cell Line	PC-12	Rattus norvegicus	EC50	=	7200.0	nM	PMID[569759]

☑ 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 NPC275104 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	336
0.1-0.2	3398
0.2-0.3	11194
0.3-0.4	8729
0.4-0.5	8510
0.5-0.6	8020
0.6-0.7	2067
0.7-0.8	395
0.8-0.85	43
0.85-0.9	4
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
0.8737	High Similarity	NPC45040
0.8587	High Similarity	NPC265146
0.8557	High Similarity	NPC151715
0.8557	High Similarity	NPC128062
0.8495	Intermediate Similarity	NPC248817
0.8495	Intermediate Similarity	NPC175313
0.8469	Intermediate Similarity	NPC274678
0.8469	Intermediate Similarity	NPC26244
0.8421	Intermediate Similarity	NPC104216
0.8404	Intermediate Similarity	NPC197783
0.8387	Intermediate Similarity	NPC124436
0.8384	Intermediate Similarity	NPC292730
0.8384	Intermediate Similarity	NPC473388
0.8384	Intermediate Similarity	NPC132271
0.8384	Intermediate Similarity	NPC82664
0.8384	Intermediate Similarity	NPC216520
0.8316	Intermediate Similarity	NPC23167
0.8316	Intermediate Similarity	NPC184169
0.83	Intermediate Similarity	NPC201967
0.8247	Intermediate Similarity	NPC300017
0.8229	Intermediate Similarity	NPC25493
0.8229	Intermediate Similarity	NPC113460
0.8218	Intermediate Similarity	NPC130193
0.8218	Intermediate Similarity	NPC216468
0.8218	Intermediate Similarity	NPC51333
0.8218	Intermediate Similarity	NPC78119
0.8218	Intermediate Similarity	NPC92730
0.8218	Intermediate Similarity	NPC132078
0.8163	Intermediate Similarity	NPC270547
0.8144	Intermediate Similarity	NPC123273
0.8144	Intermediate Similarity	NPC242240
0.8144	Intermediate Similarity	NPC280347
0.8144	Intermediate Similarity	NPC98772
0.8144	Intermediate Similarity	NPC258219
0.8144	Intermediate Similarity	NPC318325
0.8144	Intermediate Similarity	NPC177420
0.8137	Intermediate Similarity	NPC223393
0.8137	Intermediate Similarity	NPC213730
0.8137	Intermediate Similarity	NPC161571
0.8137	Intermediate Similarity	NPC275053
0.8137	Intermediate Similarity	NPC248573
0.8119	Intermediate Similarity	NPC32674
0.8119	Intermediate Similarity	NPC225464
0.8081	Intermediate Similarity	NPC138117
0.8081	Intermediate Similarity	NPC181709
0.8081	Intermediate Similarity	NPC325292
0.8081	Intermediate Similarity	NPC271440
0.8061	Intermediate Similarity	NPC55561
0.8061	Intermediate Similarity	NPC300478
0.8058	Intermediate Similarity	NPC40258
0.8058	Intermediate Similarity	NPC91461
0.8058	Intermediate Similarity	NPC7686
0.8021	Intermediate Similarity	NPC155393
0.8	Intermediate Similarity	NPC32977
0.8	Intermediate Similarity	NPC81010
0.8	Intermediate Similarity	NPC76938
0.7981	Intermediate Similarity	NPC68269
0.7981	Intermediate Similarity	NPC135784
0.7981	Intermediate Similarity	NPC168829
0.798	Intermediate Similarity	NPC155908
0.798	Intermediate Similarity	NPC204210
0.798	Intermediate Similarity	NPC304541
0.7941	Intermediate Similarity	NPC291789
0.7938	Intermediate Similarity	NPC407
0.7938	Intermediate Similarity	NPC307235
0.7921	Intermediate Similarity	NPC286006
0.7921	Intermediate Similarity	NPC32714
0.7921	Intermediate Similarity	NPC313650
0.7917	Intermediate Similarity	NPC150837
0.7917	Intermediate Similarity	NPC286904
0.7905	Intermediate Similarity	NPC120693
0.7905	Intermediate Similarity	NPC474603
0.7905	Intermediate Similarity	NPC119860
0.7905	Intermediate Similarity	NPC261573
0.7905	Intermediate Similarity	NPC12987
0.7905	Intermediate Similarity	NPC30506
0.7905	Intermediate Similarity	NPC471511
0.7905	Intermediate Similarity	NPC288411
0.7905	Intermediate Similarity	NPC8931
0.7857	Intermediate Similarity	NPC27974
0.783	Intermediate Similarity	NPC292452
0.783	Intermediate Similarity	NPC154899
0.783	Intermediate Similarity	NPC138942
0.783	Intermediate Similarity	NPC474839
0.783	Intermediate Similarity	NPC239291
0.783	Intermediate Similarity	NPC233396
0.7822	Intermediate Similarity	NPC27323
0.7822	Intermediate Similarity	NPC316301
0.7788	Intermediate Similarity	NPC294741
0.7778	Intermediate Similarity	NPC70436
0.7767	Intermediate Similarity	NPC260000
0.7767	Intermediate Similarity	NPC156313
0.7767	Intermediate Similarity	NPC107619
0.7767	Intermediate Similarity	NPC109955
0.7757	Intermediate Similarity	NPC69332
0.7757	Intermediate Similarity	NPC95178
0.7757	Intermediate Similarity	NPC135464
0.7757	Intermediate Similarity	NPC113457
0.7757	Intermediate Similarity	NPC70843
0.7757	Intermediate Similarity	NPC54765
0.7757	Intermediate Similarity	NPC248904
0.7757	Intermediate Similarity	NPC92623
0.7757	Intermediate Similarity	NPC29989
0.7757	Intermediate Similarity	NPC188677
0.7745	Intermediate Similarity	NPC107522
0.7745	Intermediate Similarity	NPC8392
0.7736	Intermediate Similarity	NPC327811
0.7736	Intermediate Similarity	NPC254965
0.7714	Intermediate Similarity	NPC12221
0.7714	Intermediate Similarity	NPC143659
0.7714	Intermediate Similarity	NPC100340
0.77	Intermediate Similarity	NPC312304
0.77	Intermediate Similarity	NPC47950
0.77	Intermediate Similarity	NPC192
0.77	Intermediate Similarity	NPC151764
0.7692	Intermediate Similarity	NPC80027
0.7692	Intermediate Similarity	NPC245561
0.7692	Intermediate Similarity	NPC280869
0.7692	Intermediate Similarity	NPC128723
0.7692	Intermediate Similarity	NPC171843
0.7692	Intermediate Similarity	NPC131587
0.7685	Intermediate Similarity	NPC260952
0.7685	Intermediate Similarity	NPC176527
0.7677	Intermediate Similarity	NPC19680
0.767	Intermediate Similarity	NPC202986
0.7642	Intermediate Similarity	NPC233827
0.7642	Intermediate Similarity	NPC168393
0.7624	Intermediate Similarity	NPC231150
0.7624	Intermediate Similarity	NPC306074
0.7619	Intermediate Similarity	NPC253746
0.7619	Intermediate Similarity	NPC52472
0.7615	Intermediate Similarity	NPC262365
0.7615	Intermediate Similarity	NPC233835
0.7615	Intermediate Similarity	NPC11554
0.7615	Intermediate Similarity	NPC75440
0.7615	Intermediate Similarity	NPC471495
0.7615	Intermediate Similarity	NPC61885
0.7615	Intermediate Similarity	NPC206341
0.7615	Intermediate Similarity	NPC17525
0.7615	Intermediate Similarity	NPC96224
0.7615	Intermediate Similarity	NPC95344
0.7615	Intermediate Similarity	NPC24101
0.7615	Intermediate Similarity	NPC34864
0.7615	Intermediate Similarity	NPC201959
0.7615	Intermediate Similarity	NPC58427
0.7615	Intermediate Similarity	NPC105727
0.7615	Intermediate Similarity	NPC114392
0.7615	Intermediate Similarity	NPC63698
0.7615	Intermediate Similarity	NPC153690
0.7596	Intermediate Similarity	NPC140619
0.7596	Intermediate Similarity	NPC77492
0.7593	Intermediate Similarity	NPC271274
0.7573	Intermediate Similarity	NPC257182
0.7573	Intermediate Similarity	NPC246679
0.757	Intermediate Similarity	NPC241891
0.757	Intermediate Similarity	NPC323810
0.757	Intermediate Similarity	NPC102216
0.7549	Intermediate Similarity	NPC306884
0.7549	Intermediate Similarity	NPC162314
0.7549	Intermediate Similarity	NPC3358
0.7549	Intermediate Similarity	NPC94139
0.7549	Intermediate Similarity	NPC147284
0.7549	Intermediate Similarity	NPC55903
0.7549	Intermediate Similarity	NPC210497
0.7549	Intermediate Similarity	NPC29373
0.7547	Intermediate Similarity	NPC101025
0.7547	Intermediate Similarity	NPC471578
0.7547	Intermediate Similarity	NPC472585
0.7547	Intermediate Similarity	NPC110764
0.7545	Intermediate Similarity	NPC88141
0.7545	Intermediate Similarity	NPC55617
0.7545	Intermediate Similarity	NPC254833
0.7545	Intermediate Similarity	NPC79543
0.7545	Intermediate Similarity	NPC228343
0.7545	Intermediate Similarity	NPC265211
0.7545	Intermediate Similarity	NPC202647
0.7545	Intermediate Similarity	NPC306045
0.7545	Intermediate Similarity	NPC62258
0.7524	Intermediate Similarity	NPC252821
0.7524	Intermediate Similarity	NPC125732
0.7524	Intermediate Similarity	NPC122005
0.75	Intermediate Similarity	NPC283711
0.75	Intermediate Similarity	NPC127676
0.75	Intermediate Similarity	NPC134829
0.75	Intermediate Similarity	NPC99557
0.75	Intermediate Similarity	NPC219286
0.7477	Intermediate Similarity	NPC63345
0.7477	Intermediate Similarity	NPC178902
0.7477	Intermediate Similarity	NPC470202
0.7477	Intermediate Similarity	NPC62351
0.7477	Intermediate Similarity	NPC321252
0.7477	Intermediate Similarity	NPC475018
0.7477	Intermediate Similarity	NPC174096
0.7477	Intermediate Similarity	NPC116842
0.7477	Intermediate Similarity	NPC473358
0.7477	Intermediate Similarity	NPC477802
0.7477	Intermediate Similarity	NPC44732
0.7477	Intermediate Similarity	NPC120982
0.7477	Intermediate Similarity	NPC196479
0.7477	Intermediate Similarity	NPC147634

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 NPC275104 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	326
0.1-0.2	1124
0.2-0.3	1468
0.3-0.4	3013
0.4-0.5	1994
0.5-0.6	966
0.6-0.7	231
0.7-0.8	21
0.8-0.85	5
0.85-0.9	2
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.8557	High Similarity	NPD2934	Approved
0.8557	High Similarity	NPD2933	Approved
0.8469	Intermediate Similarity	NPD2859	Approved
0.8469	Intermediate Similarity	NPD2860	Approved
0.8387	Intermediate Similarity	NPD111	Approved
0.8218	Intermediate Similarity	NPD3020	Approved
0.8137	Intermediate Similarity	NPD1242	Phase 1
0.7822	Intermediate Similarity	NPD1432	Clinical (unspecified phase)
0.7547	Intermediate Similarity	NPD846	Approved
0.7547	Intermediate Similarity	NPD940	Approved
0.7545	Intermediate Similarity	NPD3022	Approved
0.7545	Intermediate Similarity	NPD3021	Approved
0.7453	Intermediate Similarity	NPD3028	Approved
0.7431	Intermediate Similarity	NPD968	Approved
0.7414	Intermediate Similarity	NPD7330	Discontinued
0.7404	Intermediate Similarity	NPD844	Approved
0.7404	Intermediate Similarity	NPD1809	Phase 2
0.7391	Intermediate Similarity	NPD9087	Approved
0.7379	Intermediate Similarity	NPD845	Approved
0.7373	Intermediate Similarity	NPD1671	Clinical (unspecified phase)
0.7333	Intermediate Similarity	NPD288	Approved
0.729	Intermediate Similarity	NPD289	Clinical (unspecified phase)
0.7263	Intermediate Similarity	NPD9088	Approved
0.7248	Intermediate Similarity	NPD9608	Approved
0.7248	Intermediate Similarity	NPD9610	Approved
0.7227	Intermediate Similarity	NPD3143	Discontinued
0.713	Intermediate Similarity	NPD2228	Approved
0.713	Intermediate Similarity	NPD2229	Approved
0.713	Intermediate Similarity	NPD2234	Approved
0.7103	Intermediate Similarity	NPD9273	Approved
0.708	Intermediate Similarity	NPD9380	Clinical (unspecified phase)
0.7054	Intermediate Similarity	NPD2342	Discontinued
0.7031	Intermediate Similarity	NPD4340	Discontinued
0.7	Intermediate Similarity	NPD6867	Clinical (unspecified phase)
0.7	Intermediate Similarity	NPD7743	Approved
0.7	Intermediate Similarity	NPD6866	Clinical (unspecified phase)
0.7	Intermediate Similarity	NPD7742	Approved
0.6979	Remote Similarity	NPD9294	Approved
0.6975	Remote Similarity	NPD1548	Phase 1
0.697	Remote Similarity	NPD9089	Approved
0.6957	Remote Similarity	NPD228	Approved
0.6953	Remote Similarity	NPD468	Phase 1
0.6949	Remote Similarity	NPD7636	Approved
0.6935	Remote Similarity	NPD4339	Clinical (unspecified phase)
0.693	Remote Similarity	NPD1792	Phase 2
0.6923	Remote Similarity	NPD1476	Clinical (unspecified phase)
0.6923	Remote Similarity	NPD475	Phase 2
0.6916	Remote Similarity	NPD5206	Clinical (unspecified phase)
0.6903	Remote Similarity	NPD9265	Clinical (unspecified phase)
0.6897	Remote Similarity	NPD9379	Approved
0.6897	Remote Similarity	NPD7635	Approved
0.6897	Remote Similarity	NPD9377	Approved
0.6875	Remote Similarity	NPD3058	Clinical (unspecified phase)
0.6869	Remote Similarity	NPD9093	Approved
0.686	Remote Similarity	NPD2286	Discontinued
0.686	Remote Similarity	NPD5238	Clinical (unspecified phase)
0.6847	Remote Similarity	NPD9500	Approved
0.6833	Remote Similarity	NPD5304	Approved
0.6833	Remote Similarity	NPD5303	Approved
0.6833	Remote Similarity	NPD3091	Approved
0.6814	Remote Similarity	NPD1444	Approved
0.6814	Remote Similarity	NPD1445	Approved
0.6803	Remote Similarity	NPD3421	Phase 3
0.6783	Remote Similarity	NPD5451	Approved
0.6783	Remote Similarity	NPD4750	Phase 3
0.6777	Remote Similarity	NPD4093	Discontinued
0.6772	Remote Similarity	NPD682	Discontinued
0.6752	Remote Similarity	NPD1105	Clinical (unspecified phase)
0.6748	Remote Similarity	NPD1535	Discovery
0.6748	Remote Similarity	NPD1610	Phase 2
0.6742	Remote Similarity	NPD3846	Clinical (unspecified phase)
0.6724	Remote Similarity	NPD9280	Clinical (unspecified phase)
0.6723	Remote Similarity	NPD255	Approved
0.6723	Remote Similarity	NPD256	Approved
0.6721	Remote Similarity	NPD3019	Approved
0.6721	Remote Similarity	NPD4589	Approved
0.6721	Remote Similarity	NPD2932	Approved
0.6721	Remote Similarity	NPD4059	Approved
0.6696	Remote Similarity	NPD2684	Approved
0.6694	Remote Similarity	NPD2561	Approved
0.6694	Remote Similarity	NPD1481	Phase 2
0.6694	Remote Similarity	NPD3070	Discontinued
0.6694	Remote Similarity	NPD2562	Approved
0.6694	Remote Similarity	NPD1244	Clinical (unspecified phase)
0.6694	Remote Similarity	NPD2337	Clinical (unspecified phase)
0.6667	Remote Similarity	NPD1628	Approved
0.6667	Remote Similarity	NPD6124	Clinical (unspecified phase)
0.6667	Remote Similarity	NPD9568	Approved
0.6667	Remote Similarity	NPD5698	Clinical (unspecified phase)
0.6667	Remote Similarity	NPD1629	Approved
0.6667	Remote Similarity	NPD9295	Approved
0.6642	Remote Similarity	NPD7440	Discontinued
0.664	Remote Similarity	NPD4379	Clinical (unspecified phase)
0.664	Remote Similarity	NPD4659	Approved
0.664	Remote Similarity	NPD6583	Phase 3
0.664	Remote Similarity	NPD3600	Clinical (unspecified phase)
0.664	Remote Similarity	NPD6582	Phase 2
0.6639	Remote Similarity	NPD4235	Clinical (unspecified phase)
0.6613	Remote Similarity	NPD3092	Approved
0.6612	Remote Similarity	NPD317	Approved
0.6612	Remote Similarity	NPD856	Approved
0.6612	Remote Similarity	NPD318	Approved
0.6612	Remote Similarity	NPD16	Approved
0.661	Remote Similarity	NPD5535	Approved
0.661	Remote Similarity	NPD5277	Phase 2
0.661	Remote Similarity	NPD821	Approved
0.6609	Remote Similarity	NPD290	Approved
0.6602	Remote Similarity	NPD9073	Approved
0.6587	Remote Similarity	NPD5310	Approved
0.6587	Remote Similarity	NPD5311	Approved
0.6585	Remote Similarity	NPD2107	Clinical (unspecified phase)
0.6585	Remote Similarity	NPD1751	Approved
0.6585	Remote Similarity	NPD3095	Discontinued
0.6583	Remote Similarity	NPD6671	Approved
0.6571	Remote Similarity	NPD9094	Approved
0.6562	Remote Similarity	NPD4212	Discontinued
0.6557	Remote Similarity	NPD9545	Approved
0.6557	Remote Similarity	NPD1894	Discontinued
0.6555	Remote Similarity	NPD5283	Phase 1
0.6555	Remote Similarity	NPD7159	Clinical (unspecified phase)
0.6552	Remote Similarity	NPD74	Approved
0.6552	Remote Similarity	NPD9266	Approved
0.6544	Remote Similarity	NPD3599	Approved
0.6535	Remote Similarity	NPD3053	Approved
0.6535	Remote Similarity	NPD4104	Clinical (unspecified phase)
0.6535	Remote Similarity	NPD4103	Phase 2
0.6535	Remote Similarity	NPD3055	Approved
0.6535	Remote Similarity	NPD1164	Approved
0.6532	Remote Similarity	NPD3847	Discontinued
0.6529	Remote Similarity	NPD7325	Clinical (unspecified phase)
0.6522	Remote Similarity	NPD3134	Approved
0.6519	Remote Similarity	NPD6800	Clinical (unspecified phase)
0.65	Remote Similarity	NPD7303	Discontinued
0.65	Remote Similarity	NPD9614	Approved
0.65	Remote Similarity	NPD9618	Approved
0.65	Remote Similarity	NPD911	Approved
0.6496	Remote Similarity	NPD4535	Phase 3
0.6489	Remote Similarity	NPD4248	Discontinued
0.6486	Remote Similarity	NPD9095	Approved
0.6486	Remote Similarity	NPD9096	Approved
0.6486	Remote Similarity	NPD68	Approved
0.6486	Remote Similarity	NPD9097	Approved
0.6484	Remote Similarity	NPD6584	Phase 3
0.6484	Remote Similarity	NPD7451	Discontinued
0.648	Remote Similarity	NPD1201	Approved
0.648	Remote Similarity	NPD422	Phase 1
0.6471	Remote Similarity	NPD7843	Approved
0.6466	Remote Similarity	NPD1358	Approved
0.6466	Remote Similarity	NPD9267	Approved
0.6466	Remote Similarity	NPD9264	Approved
0.6466	Remote Similarity	NPD9263	Approved
0.6452	Remote Similarity	NPD5846	Approved
0.6452	Remote Similarity	NPD2668	Approved
0.6452	Remote Similarity	NPD6516	Phase 2
0.6452	Remote Similarity	NPD9384	Approved
0.6452	Remote Similarity	NPD9381	Approved
0.6452	Remote Similarity	NPD2667	Approved
0.6446	Remote Similarity	NPD709	Approved
0.6444	Remote Similarity	NPD2862	Discontinued
0.6434	Remote Similarity	NPD2861	Phase 2
0.6423	Remote Similarity	NPD1652	Phase 2
0.6423	Remote Similarity	NPD4127	Clinical (unspecified phase)
0.6423	Remote Similarity	NPD2226	Clinical (unspecified phase)
0.6423	Remote Similarity	NPD1182	Approved
0.6406	Remote Similarity	NPD3094	Phase 2
0.64	Remote Similarity	NPD1981	Approved
0.64	Remote Similarity	NPD1983	Approved
0.64	Remote Similarity	NPD1980	Approved
0.6397	Remote Similarity	NPD3540	Phase 1
0.6393	Remote Similarity	NPD9493	Approved
0.6393	Remote Similarity	NPD405	Clinical (unspecified phase)
0.6385	Remote Similarity	NPD4908	Phase 1
0.6385	Remote Similarity	NPD1529	Clinical (unspecified phase)
0.6378	Remote Similarity	NPD7876	Discontinued
0.6372	Remote Similarity	NPD1616	Discontinued
0.6371	Remote Similarity	NPD1357	Approved
0.637	Remote Similarity	NPD3152	Clinical (unspecified phase)
0.6364	Remote Similarity	NPD4062	Phase 3
0.6364	Remote Similarity	NPD1793	Approved
0.6364	Remote Similarity	NPD9296	Approved
0.6364	Remote Similarity	NPD1791	Approved
0.6364	Remote Similarity	NPD497	Approved
0.6349	Remote Similarity	NPD5350	Clinical (unspecified phase)
0.6349	Remote Similarity	NPD5351	Clinical (unspecified phase)
0.6349	Remote Similarity	NPD4480	Approved
0.6348	Remote Similarity	NPD1237	Approved
0.6341	Remote Similarity	NPD5536	Phase 2
0.6341	Remote Similarity	NPD9615	Approved
0.6341	Remote Similarity	NPD9613	Approved
0.6341	Remote Similarity	NPD9616	Approved
0.6336	Remote Similarity	NPD3027	Phase 3
0.633	Remote Similarity	NPD159	Clinical (unspecified phase)
0.6328	Remote Similarity	NPD1283	Approved
0.6324	Remote Similarity	NPD3539	Phase 1
0.6311	Remote Similarity	NPD7157	Approved
0.6308	Remote Similarity	NPD5736	Approved
0.6308	Remote Similarity	NPD1530	Clinical (unspecified phase)
0.6299	Remote Similarity	NPD1877	Discontinued
0.6293	Remote Similarity	NPD9697	Approved
0.629	Remote Similarity	NPD1759	Phase 1

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