NPASS Compound

Structure

Physi-Chem Properties

Molecular Weight:	219.09
Volume:	217.261
LogP:	0.177
LogD:	0.892
LogS:	-2.076
# Rotatable Bonds:	0
TPSA:	60.77
# H-Bond Aceptor:	4
# H-Bond Donor:	2
# Rings:	3
# Heavy Atoms:	4

MedChem Properties

QED Drug-Likeness Score:	0.647
Synthetic Accessibility Score:	2.913
Fsp3:	0.417
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Accepted
GSK Rule:	Accepted
BMS Rule:	0
Golden Triangle Rule:	Accepted
Chelating Alert:	1
PAINS Alert:	1

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-4.729
MDCK Permeability:	7.672464562347159e-06
Pgp-inhibitor:	0.002
Pgp-substrate:	0.845
Human Intestinal Absorption (HIA):	0.04
20% Bioavailability (F20%):	0.988
30% Bioavailability (F30%):	0.972

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.079
Plasma Protein Binding (PPB):	48.897972106933594%
Volume Distribution (VD):	0.907
Pgp-substrate:	41.18227005004883%

ADMET: Metabolism

CYP1A2-inhibitor:	0.05
CYP1A2-substrate:	0.404
CYP2C19-inhibitor:	0.067
CYP2C19-substrate:	0.088
CYP2C9-inhibitor:	0.168
CYP2C9-substrate:	0.773
CYP2D6-inhibitor:	0.011
CYP2D6-substrate:	0.31
CYP3A4-inhibitor:	0.021
CYP3A4-substrate:	0.207

ADMET: Excretion

Clearance (CL):	17.071
Half-life (T1/2):	0.827

ADMET: Toxicity

hERG Blockers:	0.02
Human Hepatotoxicity (H-HT):	0.385
Drug-inuced Liver Injury (DILI):	0.062
AMES Toxicity:	0.299
Rat Oral Acute Toxicity:	0.041
Maximum Recommended Daily Dose:	0.947
Skin Sensitization:	0.927
Carcinogencity:	0.045
Eye Corrosion:	0.003
Eye Irritation:	0.032
Respiratory Toxicity:	0.096

Download Data

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

Natural Product: NPC125852

Natural Product ID:	NPC125852
*Common Name:**	(+/-)-Trolline
IUPAC Name:	8,9-dihydroxy-2,5,6,10b-tetrahydro-1H-pyrrolo[2,1-a]isoquinolin-3-one
Synonyms:	(+/-)-Trolline
Standard InCHIKey:	LJIDRFNRDLYHNC-UHFFFAOYSA-N
Standard InCHI:	InChI=1S/C12H13NO3/c14-10-5-7-3-4-13-9(1-2-12(13)16)8(7)6-11(10)15/h5-6,9,14-15H,1-4H2
SMILES:	O=C1CCC2N1CCc1c2cc(c(c1)O)O
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL2160181
PubChem CID:	21574476
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0002955] Tetrahydroisoquinolines

*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
NPO4640	Portulaca oleracea	Species	Portulacaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[26562741]
NPO4640	Portulaca oleracea	Species	Portulacaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[29517238]
NPO4640	Portulaca oleracea	Species	Portulacaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[31625751]
NPO4640	Portulaca oleracea	Species	Portulacaceae	Eukaryota	n.a.	Along the Valencian coast, Spain	2020-Jun&Jul	PMID[35161358]
NPO4640	Portulaca oleracea	Species	Portulacaceae	Eukaryota	Herb	n.a.	n.a.	Database[FooDB]
NPO4640	Portulaca oleracea	Species	Portulacaceae	Eukaryota	Plant	n.a.	n.a.	Database[FooDB]
NPO4640	Portulaca oleracea	Species	Portulacaceae	Eukaryota	Seed	n.a.	n.a.	Database[FooDB]
NPO4640	Portulaca oleracea	Species	Portulacaceae	Eukaryota		n.a.	n.a.	Database[FooDB]
NPO4640	Portulaca oleracea	Species	Portulacaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO11697	Cirsium setosum	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO11697	Cirsium setosum	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO4640	Portulaca oleracea	Species	Portulacaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO19361	Herba meconpsis integrifoliae	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[TCMID]
NPO4640	Portulaca oleracea	Species	Portulacaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO11697	Cirsium setosum	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO4640	Portulaca oleracea	Species	Portulacaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO11697	Cirsium setosum	Species	Asteraceae	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
Others	7

Activity Type	# Activity
Organism	7

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT1286	Organism	Pectobacterium carotovorum	Pectobacterium carotovorum	IZ	=	0.0	mm	PMID[518907]
NPT19	Organism	Escherichia coli	Escherichia coli	IZ	=	0.0	mm	PMID[518907]
NPT1242	Organism	Salmonella typhi	Salmonella enterica subsp. enterica serovar Typhi	IZ	=	0.0	mm	PMID[518907]
NPT175	Organism	Enterococcus faecalis	Enterococcus faecalis	IZ	=	0.0	mm	PMID[518907]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	IZ	=	0.0	mm	PMID[518907]
NPT314	Organism	Bacillus cereus	Bacillus cereus	IZ	=	6.66	mm	PMID[518907]

☑ 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 NPC125852 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	252
0.1-0.2	1258
0.2-0.3	6086
0.3-0.4	11644
0.4-0.5	10350
0.5-0.6	11010
0.6-0.7	1781
0.7-0.8	294
0.8-0.85	20
0.85-0.9	0
0.9-0.95	0
0.95-1	2

Similarity Score	Similarity Level	Natural Product ID
0.8369	Intermediate Similarity	NPC300020
0.8369	Intermediate Similarity	NPC33338
0.8369	Intermediate Similarity	NPC302171
0.8151	Intermediate Similarity	NPC219233
0.8151	Intermediate Similarity	NPC211468
0.8151	Intermediate Similarity	NPC170170
0.8095	Intermediate Similarity	NPC323123
0.8089	Intermediate Similarity	NPC135006
0.7891	Intermediate Similarity	NPC301050
0.7891	Intermediate Similarity	NPC131204
0.7843	Intermediate Similarity	NPC179825
0.7843	Intermediate Similarity	NPC191376
0.7843	Intermediate Similarity	NPC321505
0.7792	Intermediate Similarity	NPC246587
0.7792	Intermediate Similarity	NPC24233
0.7792	Intermediate Similarity	NPC428
0.7792	Intermediate Similarity	NPC135538
0.7792	Intermediate Similarity	NPC147390
0.7792	Intermediate Similarity	NPC476571
0.7785	Intermediate Similarity	NPC147091
0.7763	Intermediate Similarity	NPC294249
0.7712	Intermediate Similarity	NPC185838
0.7692	Intermediate Similarity	NPC97221
0.7692	Intermediate Similarity	NPC88249
0.7692	Intermediate Similarity	NPC151895
0.7692	Intermediate Similarity	NPC220858
0.7692	Intermediate Similarity	NPC192768
0.7643	Intermediate Similarity	NPC119669
0.764	Intermediate Similarity	NPC205167
0.764	Intermediate Similarity	NPC249274
0.7628	Intermediate Similarity	NPC103379
0.7628	Intermediate Similarity	NPC477565
0.7616	Intermediate Similarity	NPC251439
0.7595	Intermediate Similarity	NPC133011
0.7595	Intermediate Similarity	NPC82285
0.7584	Intermediate Similarity	NPC109580
0.7578	Intermediate Similarity	NPC111485
0.7569	Intermediate Similarity	NPC318965
0.7557	Intermediate Similarity	NPC24228
0.7533	Intermediate Similarity	NPC242159
0.7533	Intermediate Similarity	NPC313694
0.7532	Intermediate Similarity	NPC76213
0.7532	Intermediate Similarity	NPC277669
0.75	Intermediate Similarity	NPC278799
0.75	Intermediate Similarity	NPC476151
0.75	Intermediate Similarity	NPC5238
0.75	Intermediate Similarity	NPC207757
0.75	Intermediate Similarity	NPC2413
0.75	Intermediate Similarity	NPC276588
0.75	Intermediate Similarity	NPC39701
0.75	Intermediate Similarity	NPC204828
0.75	Intermediate Similarity	NPC469817
0.75	Intermediate Similarity	NPC54379
0.75	Intermediate Similarity	NPC249797
0.75	Intermediate Similarity	NPC110416
0.75	Intermediate Similarity	NPC295691
0.75	Intermediate Similarity	NPC172765
0.75	Intermediate Similarity	NPC184026
0.75	Intermediate Similarity	NPC193949
0.75	Intermediate Similarity	NPC189266
0.75	Intermediate Similarity	NPC127674
0.7485	Intermediate Similarity	NPC102760
0.7484	Intermediate Similarity	NPC223124
0.7468	Intermediate Similarity	NPC297322
0.7466	Intermediate Similarity	NPC145888
0.7466	Intermediate Similarity	NPC161593
0.7466	Intermediate Similarity	NPC16031
0.7453	Intermediate Similarity	NPC186063
0.7432	Intermediate Similarity	NPC257390
0.7405	Intermediate Similarity	NPC60538
0.7405	Intermediate Similarity	NPC207824
0.7394	Intermediate Similarity	NPC238530
0.7394	Intermediate Similarity	NPC232514
0.7394	Intermediate Similarity	NPC276944
0.7386	Intermediate Similarity	NPC314682
0.7386	Intermediate Similarity	NPC473941
0.7379	Intermediate Similarity	NPC171372
0.7375	Intermediate Similarity	NPC37272
0.7365	Intermediate Similarity	NPC160193
0.7365	Intermediate Similarity	NPC470324
0.7365	Intermediate Similarity	NPC477185
0.7358	Intermediate Similarity	NPC274026
0.7358	Intermediate Similarity	NPC223125
0.7356	Intermediate Similarity	NPC230098
0.7351	Intermediate Similarity	NPC6913
0.7338	Intermediate Similarity	NPC328750
0.7338	Intermediate Similarity	NPC188163
0.7338	Intermediate Similarity	NPC474915
0.7338	Intermediate Similarity	NPC213206
0.7337	Intermediate Similarity	NPC256935
0.7329	Intermediate Similarity	NPC2295
0.7329	Intermediate Similarity	NPC477564
0.7321	Intermediate Similarity	NPC475688
0.732	Intermediate Similarity	NPC231572
0.7317	Intermediate Similarity	NPC27410
0.7317	Intermediate Similarity	NPC215829
0.7317	Intermediate Similarity	NPC166014
0.7317	Intermediate Similarity	NPC97072
0.7305	Intermediate Similarity	NPC210140
0.7303	Intermediate Similarity	NPC7018
0.7283	Intermediate Similarity	NPC116284
0.7279	Intermediate Similarity	NPC321561
0.7278	Intermediate Similarity	NPC267414
0.7267	Intermediate Similarity	NPC88667
0.7267	Intermediate Similarity	NPC26601
0.7267	Intermediate Similarity	NPC474745
0.7255	Intermediate Similarity	NPC253429
0.7254	Intermediate Similarity	NPC85276
0.7251	Intermediate Similarity	NPC222524
0.725	Intermediate Similarity	NPC68967
0.7244	Intermediate Similarity	NPC136860
0.7244	Intermediate Similarity	NPC128019
0.7244	Intermediate Similarity	NPC476567
0.7235	Intermediate Similarity	NPC477187
0.7233	Intermediate Similarity	NPC475959
0.7229	Intermediate Similarity	NPC476569
0.7229	Intermediate Similarity	NPC324144
0.7229	Intermediate Similarity	NPC1229
0.7209	Intermediate Similarity	NPC73555
0.7209	Intermediate Similarity	NPC474325
0.7208	Intermediate Similarity	NPC150712
0.7202	Intermediate Similarity	NPC181653
0.7202	Intermediate Similarity	NPC190332
0.7202	Intermediate Similarity	NPC100566
0.7197	Intermediate Similarity	NPC16188
0.7195	Intermediate Similarity	NPC475326
0.7188	Intermediate Similarity	NPC469539
0.7188	Intermediate Similarity	NPC469540
0.7186	Intermediate Similarity	NPC284183
0.7186	Intermediate Similarity	NPC231198
0.7186	Intermediate Similarity	NPC78222
0.7186	Intermediate Similarity	NPC212794
0.7186	Intermediate Similarity	NPC306843
0.7186	Intermediate Similarity	NPC136508
0.7186	Intermediate Similarity	NPC477563
0.7186	Intermediate Similarity	NPC4138
0.7186	Intermediate Similarity	NPC96603
0.7186	Intermediate Similarity	NPC24465
0.7186	Intermediate Similarity	NPC134858
0.7186	Intermediate Similarity	NPC196447
0.7186	Intermediate Similarity	NPC13504
0.7186	Intermediate Similarity	NPC121275
0.7186	Intermediate Similarity	NPC253043
0.7168	Intermediate Similarity	NPC99723
0.7162	Intermediate Similarity	NPC305717
0.716	Intermediate Similarity	NPC241055
0.7159	Intermediate Similarity	NPC477259
0.7159	Intermediate Similarity	NPC169387
0.7152	Intermediate Similarity	NPC130926
0.7152	Intermediate Similarity	NPC208757
0.7151	Intermediate Similarity	NPC237044
0.7151	Intermediate Similarity	NPC475120
0.7143	Intermediate Similarity	NPC264850
0.7143	Intermediate Similarity	NPC475981
0.7143	Intermediate Similarity	NPC13916
0.7143	Intermediate Similarity	NPC268503
0.7143	Intermediate Similarity	NPC240841
0.7143	Intermediate Similarity	NPC225745
0.7143	Intermediate Similarity	NPC250846
0.7143	Intermediate Similarity	NPC317272
0.7143	Intermediate Similarity	NPC256012
0.7143	Intermediate Similarity	NPC42549
0.7143	Intermediate Similarity	NPC474746
0.7133	Intermediate Similarity	NPC120251
0.7126	Intermediate Similarity	NPC233650
0.7126	Intermediate Similarity	NPC320104
0.7114	Intermediate Similarity	NPC268763
0.7114	Intermediate Similarity	NPC66177
0.7114	Intermediate Similarity	NPC8305
0.711	Intermediate Similarity	NPC21885
0.7108	Intermediate Similarity	NPC226428
0.7107	Intermediate Similarity	NPC476444
0.7105	Intermediate Similarity	NPC160692
0.7101	Intermediate Similarity	NPC117188
0.7101	Intermediate Similarity	NPC306555
0.7101	Intermediate Similarity	NPC205421
0.7101	Intermediate Similarity	NPC158376
0.7101	Intermediate Similarity	NPC298979
0.7101	Intermediate Similarity	NPC474931
0.7101	Intermediate Similarity	NPC81218
0.7101	Intermediate Similarity	NPC145832
0.7101	Intermediate Similarity	NPC12053
0.7093	Intermediate Similarity	NPC128560
0.7093	Intermediate Similarity	NPC199465
0.7093	Intermediate Similarity	NPC304675
0.7093	Intermediate Similarity	NPC229166
0.7092	Intermediate Similarity	NPC142599
0.7083	Intermediate Similarity	NPC168409
0.7081	Intermediate Similarity	NPC226514
0.7081	Intermediate Similarity	NPC219162
0.7079	Intermediate Similarity	NPC82763
0.7076	Intermediate Similarity	NPC476331
0.7073	Intermediate Similarity	NPC78733
0.7071	Intermediate Similarity	NPC146422
0.7067	Intermediate Similarity	NPC124802
0.7063	Intermediate Similarity	NPC51957
0.7063	Intermediate Similarity	NPC476144
0.7063	Intermediate Similarity	NPC16107
0.7063	Intermediate Similarity	NPC210437
0.7063	Intermediate Similarity	NPC106295

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 NPC125852 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	169
0.1-0.2	596
0.2-0.3	884
0.3-0.4	1916
0.4-0.5	3101
0.5-0.6	1989
0.6-0.7	443
0.7-0.8	52
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.7829	Intermediate Similarity	NPD3845	Phase 1
0.7785	Intermediate Similarity	NPD1632	Clinical (unspecified phase)
0.7778	Intermediate Similarity	NPD2420	Approved
0.7778	Intermediate Similarity	NPD2421	Approved
0.7742	Intermediate Similarity	NPD3639	Approved
0.7742	Intermediate Similarity	NPD3640	Phase 3
0.7742	Intermediate Similarity	NPD3641	Approved
0.7712	Intermediate Similarity	NPD2422	Clinical (unspecified phase)
0.7669	Intermediate Similarity	NPD4166	Phase 2
0.7597	Intermediate Similarity	NPD6884	Clinical (unspecified phase)
0.7532	Intermediate Similarity	NPD824	Approved
0.7466	Intermediate Similarity	NPD9569	Approved
0.7456	Intermediate Similarity	NPD6297	Approved
0.7431	Intermediate Similarity	NPD1755	Approved
0.7427	Intermediate Similarity	NPD7280	Phase 3
0.7427	Intermediate Similarity	NPD7281	Phase 3
0.741	Intermediate Similarity	NPD5137	Approved
0.7365	Intermediate Similarity	NPD2898	Approved
0.7365	Intermediate Similarity	NPD9536	Phase 1
0.7365	Intermediate Similarity	NPD9537	Phase 1
0.7351	Intermediate Similarity	NPD817	Approved
0.7351	Intermediate Similarity	NPD823	Approved
0.7338	Intermediate Similarity	NPD4664	Clinical (unspecified phase)
0.7337	Intermediate Similarity	NPD5312	Approved
0.7337	Intermediate Similarity	NPD5313	Approved
0.7329	Intermediate Similarity	NPD3055	Approved
0.7329	Intermediate Similarity	NPD3053	Approved
0.7315	Intermediate Similarity	NPD2028	Clinical (unspecified phase)
0.7283	Intermediate Similarity	NPD6853	Approved
0.7283	Intermediate Similarity	NPD6851	Approved
0.7279	Intermediate Similarity	NPD258	Approved
0.7279	Intermediate Similarity	NPD257	Approved
0.7273	Intermediate Similarity	NPD5525	Clinical (unspecified phase)
0.7267	Intermediate Similarity	NPD259	Phase 1
0.7197	Intermediate Similarity	NPD7910	Clinical (unspecified phase)
0.7188	Intermediate Similarity	NPD1670	Discontinued
0.7171	Intermediate Similarity	NPD555	Phase 2
0.7143	Intermediate Similarity	NPD5311	Approved
0.7143	Intermediate Similarity	NPD5310	Approved
0.7143	Intermediate Similarity	NPD4010	Discontinued
0.7135	Intermediate Similarity	NPD6020	Phase 2
0.7117	Intermediate Similarity	NPD4772	Phase 2
0.7117	Intermediate Similarity	NPD4773	Phase 2
0.7114	Intermediate Similarity	NPD3635	Approved
0.7114	Intermediate Similarity	NPD3637	Approved
0.7114	Intermediate Similarity	NPD3636	Approved
0.7071	Intermediate Similarity	NPD9377	Approved
0.7071	Intermediate Similarity	NPD9379	Approved
0.7067	Intermediate Similarity	NPD3594	Approved
0.7067	Intermediate Similarity	NPD3595	Approved
0.7063	Intermediate Similarity	NPD4584	Approved
0.7055	Intermediate Similarity	NPD1337	Clinical (unspecified phase)
0.7039	Intermediate Similarity	NPD1132	Approved
0.7039	Intermediate Similarity	NPD1136	Approved
0.7039	Intermediate Similarity	NPD1130	Approved
0.7017	Intermediate Similarity	NPD7667	Clinical (unspecified phase)
0.7014	Intermediate Similarity	NPD2226	Clinical (unspecified phase)
0.7012	Intermediate Similarity	NPD7109	Clinical (unspecified phase)
0.7012	Intermediate Similarity	NPD7110	Phase 1
0.6993	Remote Similarity	NPD825	Approved
0.6993	Remote Similarity	NPD826	Approved
0.6987	Remote Similarity	NPD9570	Approved
0.6983	Remote Similarity	NPD2490	Approved
0.6983	Remote Similarity	NPD2488	Approved
0.6975	Remote Similarity	NPD6662	Clinical (unspecified phase)
0.6974	Remote Similarity	NPD598	Approved
0.6974	Remote Similarity	NPD601	Approved
0.6974	Remote Similarity	NPD597	Approved
0.6968	Remote Similarity	NPD743	Approved
0.6966	Remote Similarity	NPD4093	Discontinued
0.6957	Remote Similarity	NPD1754	Clinical (unspecified phase)
0.6954	Remote Similarity	NPD2605	Approved
0.6954	Remote Similarity	NPD4207	Discontinued
0.6954	Remote Similarity	NPD2606	Approved
0.6951	Remote Similarity	NPD6876	Approved
0.6951	Remote Similarity	NPD6875	Approved
0.6948	Remote Similarity	NPD275	Approved
0.6948	Remote Similarity	NPD274	Approved
0.6937	Remote Similarity	NPD3141	Discontinued
0.6932	Remote Similarity	NPD3534	Clinical (unspecified phase)
0.6923	Remote Similarity	NPD1753	Discontinued
0.6913	Remote Similarity	NPD9634	Clinical (unspecified phase)
0.6908	Remote Similarity	NPD5155	Approved
0.6908	Remote Similarity	NPD5156	Approved
0.6908	Remote Similarity	NPD2669	Clinical (unspecified phase)
0.689	Remote Similarity	NPD4017	Approved
0.6886	Remote Similarity	NPD5977	Approved
0.6886	Remote Similarity	NPD5978	Approved
0.6886	Remote Similarity	NPD5967	Approved
0.6885	Remote Similarity	NPD5564	Approved
0.6882	Remote Similarity	NPD6107	Approved
0.6875	Remote Similarity	NPD7132	Clinical (unspecified phase)
0.6872	Remote Similarity	NPD7291	Discontinued
0.686	Remote Similarity	NPD27	Approved
0.686	Remote Similarity	NPD2489	Approved
0.6857	Remote Similarity	NPD1792	Phase 2
0.6853	Remote Similarity	NPD1791	Approved
0.6853	Remote Similarity	NPD6997	Phase 2
0.6853	Remote Similarity	NPD1793	Approved
0.6846	Remote Similarity	NPD9622	Approved
0.6824	Remote Similarity	NPD7201	Clinical (unspecified phase)
0.6824	Remote Similarity	NPD2041	Clinical (unspecified phase)
0.6824	Remote Similarity	NPD2042	Clinical (unspecified phase)
0.6824	Remote Similarity	NPD5823	Approved
0.6821	Remote Similarity	NPD9620	Approved
0.6821	Remote Similarity	NPD9621	Approved
0.6821	Remote Similarity	NPD9619	Approved
0.6818	Remote Similarity	NPD7086	Phase 2
0.6803	Remote Similarity	NPD1751	Approved
0.6796	Remote Similarity	NPD3808	Clinical (unspecified phase)
0.6786	Remote Similarity	NPD2560	Approved
0.6786	Remote Similarity	NPD2563	Approved
0.6783	Remote Similarity	NPD2228	Approved
0.6783	Remote Similarity	NPD2234	Approved
0.6783	Remote Similarity	NPD2229	Approved
0.6781	Remote Similarity	NPD5303	Approved
0.6781	Remote Similarity	NPD5304	Approved
0.6779	Remote Similarity	NPD2337	Clinical (unspecified phase)
0.6774	Remote Similarity	NPD3059	Approved
0.6774	Remote Similarity	NPD3061	Approved
0.6774	Remote Similarity	NPD3062	Approved
0.677	Remote Similarity	NPD5241	Discontinued
0.6766	Remote Similarity	NPD7248	Discontinued
0.6766	Remote Similarity	NPD7298	Approved
0.6763	Remote Similarity	NPD1444	Approved
0.6763	Remote Similarity	NPD1445	Approved
0.6759	Remote Similarity	NPD9568	Approved
0.6748	Remote Similarity	NPD3645	Discontinued
0.6744	Remote Similarity	NPD6071	Discontinued
0.674	Remote Similarity	NPD6377	Clinical (unspecified phase)
0.6738	Remote Similarity	NPD3450	Approved
0.6738	Remote Similarity	NPD3452	Approved
0.673	Remote Similarity	NPD4726	Approved
0.673	Remote Similarity	NPD4725	Approved
0.673	Remote Similarity	NPD4721	Approved
0.6724	Remote Similarity	NPD7449	Clinical (unspecified phase)
0.671	Remote Similarity	NPD2674	Phase 3
0.6707	Remote Similarity	NPD7118	Clinical (unspecified phase)
0.6706	Remote Similarity	NPD7832	Clinical (unspecified phase)
0.6706	Remote Similarity	NPD7833	Phase 2
0.6706	Remote Similarity	NPD7831	Phase 2
0.6705	Remote Similarity	NPD7695	Clinical (unspecified phase)
0.6705	Remote Similarity	NPD2970	Approved
0.6705	Remote Similarity	NPD2969	Approved
0.6704	Remote Similarity	NPD8053	Approved
0.6704	Remote Similarity	NPD6618	Phase 2
0.6704	Remote Similarity	NPD8054	Approved
0.6689	Remote Similarity	NPD9384	Approved
0.6689	Remote Similarity	NPD9381	Approved
0.6688	Remote Similarity	NPD2492	Phase 1
0.6688	Remote Similarity	NPD5314	Approved
0.6687	Remote Similarity	NPD4257	Approved
0.6687	Remote Similarity	NPD4256	Phase 2
0.6667	Remote Similarity	NPD3589	Clinical (unspecified phase)
0.6667	Remote Similarity	NPD4208	Discontinued
0.6649	Remote Similarity	NPD2493	Approved
0.6649	Remote Similarity	NPD2494	Approved
0.6647	Remote Similarity	NPD3051	Approved
0.6646	Remote Similarity	NPD7718	Clinical (unspecified phase)
0.6646	Remote Similarity	NPD4127	Clinical (unspecified phase)
0.6645	Remote Similarity	NPD4104	Clinical (unspecified phase)
0.6645	Remote Similarity	NPD4103	Phase 2
0.6644	Remote Similarity	NPD2688	Clinical (unspecified phase)
0.6632	Remote Similarity	NPD4040	Phase 1
0.6628	Remote Similarity	NPD2904	Discontinued
0.6627	Remote Similarity	NPD6818	Clinical (unspecified phase)
0.6623	Remote Similarity	NPD4659	Approved
0.6623	Remote Similarity	NPD1421	Approved
0.6623	Remote Similarity	NPD1420	Approved
0.6614	Remote Similarity	NPD3448	Approved
0.6609	Remote Similarity	NPD8051	Clinical (unspecified phase)
0.66	Remote Similarity	NPD5350	Clinical (unspecified phase)
0.66	Remote Similarity	NPD5351	Clinical (unspecified phase)
0.6587	Remote Similarity	NPD3455	Phase 2
0.6585	Remote Similarity	NPD3124	Discontinued
0.6579	Remote Similarity	NPD4002	Approved
0.6579	Remote Similarity	NPD4004	Approved
0.6576	Remote Similarity	NPD5968	Phase 3
0.6575	Remote Similarity	NPD255	Approved
0.6575	Remote Similarity	NPD256	Approved
0.6571	Remote Similarity	NPD6894	Phase 1
0.6568	Remote Similarity	NPD7011	Discontinued
0.6566	Remote Similarity	NPD6030	Approved
0.6566	Remote Similarity	NPD6031	Approved
0.6557	Remote Similarity	NPD6836	Approved
0.6556	Remote Similarity	NPD4577	Approved
0.6556	Remote Similarity	NPD2971	Approved
0.6556	Remote Similarity	NPD4578	Approved
0.6556	Remote Similarity	NPD2968	Approved
0.6552	Remote Similarity	NPD1293	Approved
0.6552	Remote Similarity	NPD3598	Phase 3
0.6545	Remote Similarity	NPD4582	Approved
0.6545	Remote Similarity	NPD4583	Approved
0.6538	Remote Similarity	NPD3145	Approved
0.6538	Remote Similarity	NPD3144	Approved
0.6538	Remote Similarity	NPD4621	Approved
0.6538	Remote Similarity	NPD4619	Approved
0.6536	Remote Similarity	NPD2625	Approved
0.6536	Remote Similarity	NPD2160	Approved
0.6536	Remote Similarity	NPD2627	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