NPASS Compound

Structure

Physi-Chem Properties

Molecular Weight:	210.09
Volume:	214.871
LogP:	0.977
LogD:	1.283
LogS:	-1.796
# Rotatable Bonds:	4
TPSA:	58.92
# H-Bond Aceptor:	4
# H-Bond Donor:	2
# Rings:	1
# Heavy Atoms:	4

MedChem Properties

QED Drug-Likeness Score:	0.789
Synthetic Accessibility Score:	2.172
Fsp3:	0.273
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Accepted
GSK Rule:	Accepted
BMS Rule:	0
Golden Triangle Rule:	Accepted
Chelating Alert:	1
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-4.602
MDCK Permeability:	1.486746441514697e-05
Pgp-inhibitor:	0.002
Pgp-substrate:	0.056
Human Intestinal Absorption (HIA):	0.011
20% Bioavailability (F20%):	0.003
30% Bioavailability (F30%):	0.249

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.799
Plasma Protein Binding (PPB):	83.89459991455078%
Volume Distribution (VD):	0.702
Pgp-substrate:	15.157493591308594%

ADMET: Metabolism

CYP1A2-inhibitor:	0.558
CYP1A2-substrate:	0.875
CYP2C19-inhibitor:	0.025
CYP2C19-substrate:	0.772
CYP2C9-inhibitor:	0.019
CYP2C9-substrate:	0.679
CYP2D6-inhibitor:	0.007
CYP2D6-substrate:	0.875
CYP3A4-inhibitor:	0.022
CYP3A4-substrate:	0.237

ADMET: Excretion

Clearance (CL):	11.061
Half-life (T1/2):	0.928

ADMET: Toxicity

hERG Blockers:	0.035
Human Hepatotoxicity (H-HT):	0.212
Drug-inuced Liver Injury (DILI):	0.032
AMES Toxicity:	0.02
Rat Oral Acute Toxicity:	0.146
Maximum Recommended Daily Dose:	0.072
Skin Sensitization:	0.958
Carcinogencity:	0.439
Eye Corrosion:	0.383
Eye Irritation:	0.967
Respiratory Toxicity:	0.285

Download Data

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

Natural Product: NPC229401

Natural Product ID:	NPC229401
*Common Name:**	4-[(E)-3-Hydroxyprop-1-Enyl]-2,6-Dimethoxyphenol
IUPAC Name:	4-[(E)-3-hydroxyprop-1-enyl]-2,6-dimethoxyphenol
Synonyms:
Standard InCHIKey:	LZFOPEXOUVTGJS-ONEGZZNKSA-N
Standard InCHI:	InChI=1S/C11H14O4/c1-14-9-6-8(4-3-5-12)7-10(15-2)11(9)13/h3-4,6-7,12-13H,5H2,1-2H3/b4-3+
SMILES:	COc1cc(/C=C/CO)cc(c1O)OC
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL1800816
PubChem CID:	5280507
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0002448] Benzenoids [CHEMONTID:0000134] Phenols [CHEMONTID:0000190] Methoxyphenols

*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
NPO22079	Paulownia tomentosa	Species	Paulowniaceae	Eukaryota	fruits	n.a.	n.a.	PMID[17625893]
NPO22079	Paulownia tomentosa	Species	Paulowniaceae	Eukaryota	Fruits	n.a.	n.a.	PMID[18293924]
NPO22079	Paulownia tomentosa	Species	Paulowniaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[20192247]
NPO22079	Paulownia tomentosa	Species	Paulowniaceae	Eukaryota	n.a.	fruit	n.a.	PMID[21319773]
NPO22079	Paulownia tomentosa	Species	Paulowniaceae	Eukaryota	fruits	n.a.	n.a.	PMID[22445674]
NPO22079	Paulownia tomentosa	Species	Paulowniaceae	Eukaryota	fruits	n.a.	n.a.	PMID[23623680]
NPO22079	Paulownia tomentosa	Species	Paulowniaceae	Eukaryota	fruits	n.a.	n.a.	PMID[25735399]
NPO22079	Paulownia tomentosa	Species	Paulowniaceae	Eukaryota	Fruits	n.a.	n.a.	PMID[28322565]
NPO22079	Paulownia tomentosa	Species	Paulowniaceae	Eukaryota	Fruits	n.a.	n.a.	PMID[28968119]
NPO16066	Urtica cannabina	Species	Urticaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO22079	Paulownia tomentosa	Species	Paulowniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO22079	Paulownia tomentosa	Species	Paulowniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO16066	Urtica cannabina	Species	Urticaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO16066	Urtica cannabina	Species	Urticaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO22079	Paulownia tomentosa	Species	Paulowniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO16066	Urtica cannabina	Species	Urticaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO22079	Paulownia tomentosa	Species	Paulowniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]

☑ Note for Reference:
In addition to directly collecting NP source organism data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated them from below databases:
☉ UNPD: Universal Natural Products Database [PMID: 23638153].
☉ StreptomeDB: a database of streptomycetes natural products [PMID: 33051671].
☉ TM-MC: a database of medicinal materials and chemical compounds in Northeast Asian traditional medicine [PMID: 26156871].
☉ TCM@Taiwan: a Traditional Chinese Medicine database [PMID: 21253603].
☉ TCMID: a Traditional Chinese Medicine database [PMID: 29106634].
☉ TCMSP: The traditional Chinese medicine systems pharmacology database and analysis platform [PMID: 24735618].
☉ HerDing: a herb recommendation system to treat diseases using genes and chemicals [PMID: 26980517].
☉ MetaboLights: a metabolomics database [PMID: 27010336].
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

NP Quantity Composition/Concentration

Organism ID	NP ID	Organism Material Preparation	Organism Part	NP Quantity (Standard)	NP Quantity (Minimum)	NP Quantity (Maximum)	Quantity Unit	Reference

☑ Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP quantitative records for specific NP domains (e.g., NPS from foods or herbs) from domain-specific databases. These databases include:
☉ DUKE: Dr. Duke's Phytochemical and Ethnobotanical Databases.
☉ PHENOL EXPLORER: is the first comprehensive database on polyphenol content in foods [PMID: 24103452], its homepage can be accessed at here.
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

Biological Activity

Activity Type	# Activity
IC50	6

Activity Type	# Activity
Cell Line	4
NON-MOLECULAR	2

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT81	Cell Line	A549	Homo sapiens	IC50	>	100000.0	nM	PMID[497488]
NPT306	Cell Line	PC-3	Homo sapiens	IC50	>	100000.0	nM	PMID[497488]
NPT170	Cell Line	SK-MEL-28	Homo sapiens	IC50	>	100000.0	nM	PMID[497488]
NPT114	Cell Line	LoVo	Homo sapiens	IC50	>	100000.0	nM	PMID[497488]
NPT20529	NON-MOLECULAR	NON-PROTEIN TARGET	n.a.	IC50	>	100000.0	nM	PMID[497488]
NPT20529	NON-MOLECULAR	NON-PROTEIN TARGET	n.a.	IC50	=	80000.0	nM	PMID[497488]

☑ 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 NPC229401 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	349
0.1-0.2	1865
0.2-0.3	6607
0.3-0.4	12954
0.4-0.5	3818
0.5-0.6	5013
0.6-0.7	7890
0.7-0.8	3158
0.8-0.85	618
0.85-0.9	309
0.9-0.95	104
0.95-1	12

Similarity Score	Similarity Level	Natural Product ID
0.9732	High Similarity	NPC259638
0.9652	High Similarity	NPC49341
0.9643	High Similarity	NPC193067
0.9561	High Similarity	NPC20674
0.9487	High Similarity	NPC220598
0.9487	High Similarity	NPC165375
0.9478	High Similarity	NPC232084
0.9478	High Similarity	NPC247364
0.9478	High Similarity	NPC61516
0.9478	High Similarity	NPC10932
0.9402	High Similarity	NPC262253
0.9402	High Similarity	NPC71579
0.9402	High Similarity	NPC473411
0.9391	High Similarity	NPC226629
0.9328	High Similarity	NPC271985
0.9322	High Similarity	NPC238810
0.931	High Similarity	NPC35071
0.931	High Similarity	NPC177475
0.931	High Similarity	NPC148615
0.9304	High Similarity	NPC63083
0.9304	High Similarity	NPC255675
0.9298	High Similarity	NPC221049
0.9256	High Similarity	NPC98631
0.9256	High Similarity	NPC186843
0.9256	High Similarity	NPC206615
0.9256	High Similarity	NPC470213
0.9244	High Similarity	NPC183446
0.9231	High Similarity	NPC166759
0.9231	High Similarity	NPC199023
0.9224	High Similarity	NPC181969
0.9224	High Similarity	NPC320987
0.9196	High Similarity	NPC78918
0.9196	High Similarity	NPC139617
0.918	High Similarity	NPC48315
0.918	High Similarity	NPC476968
0.918	High Similarity	NPC170844
0.9167	High Similarity	NPC221077
0.9167	High Similarity	NPC17943
0.9167	High Similarity	NPC475169
0.9167	High Similarity	NPC193544
0.9167	High Similarity	NPC208950
0.9167	High Similarity	NPC57490
0.9167	High Similarity	NPC58279
0.9167	High Similarity	NPC233410
0.9167	High Similarity	NPC82483
0.9167	High Similarity	NPC265483
0.9167	High Similarity	NPC203133
0.9167	High Similarity	NPC116907
0.9167	High Similarity	NPC298757
0.9167	High Similarity	NPC251855
0.9167	High Similarity	NPC117214
0.9167	High Similarity	NPC472093
0.9167	High Similarity	NPC299584
0.9167	High Similarity	NPC300326
0.916	High Similarity	NPC197757
0.916	High Similarity	NPC228922
0.9153	High Similarity	NPC145780
0.9153	High Similarity	NPC470804
0.9145	High Similarity	NPC474565
0.9106	High Similarity	NPC472338
0.9098	High Similarity	NPC109275
0.9091	High Similarity	NPC78974
0.9091	High Similarity	NPC223136
0.9091	High Similarity	NPC28730
0.9091	High Similarity	NPC103823
0.9091	High Similarity	NPC18924
0.9091	High Similarity	NPC214406
0.9091	High Similarity	NPC44748
0.9083	High Similarity	NPC5796
0.9083	High Similarity	NPC206487
0.9076	High Similarity	NPC41562
0.9076	High Similarity	NPC209567
0.9076	High Similarity	NPC270326
0.906	High Similarity	NPC135961
0.9032	High Similarity	NPC470095
0.9032	High Similarity	NPC472597
0.9032	High Similarity	NPC474017
0.9032	High Similarity	NPC470096
0.9027	High Similarity	NPC203924
0.9024	High Similarity	NPC212015
0.9018	High Similarity	NPC246358
0.9018	High Similarity	NPC36108
0.9018	High Similarity	NPC165386
0.9018	High Similarity	NPC7097
0.9018	High Similarity	NPC233731
0.9016	High Similarity	NPC159968
0.9016	High Similarity	NPC324112
0.9016	High Similarity	NPC236791
0.9016	High Similarity	NPC127587
0.9016	High Similarity	NPC74817
0.9016	High Similarity	NPC82679
0.9016	High Similarity	NPC266555
0.9016	High Similarity	NPC169474
0.9016	High Similarity	NPC293054
0.9016	High Similarity	NPC246620
0.9016	High Similarity	NPC282000
0.9016	High Similarity	NPC210355
0.9016	High Similarity	NPC124452
0.9008	High Similarity	NPC60885
0.9008	High Similarity	NPC234400
0.9	High Similarity	NPC233526
0.9	High Similarity	NPC95168
0.9	High Similarity	NPC84086
0.9	High Similarity	NPC282496
0.9	High Similarity	NPC136319
0.8992	High Similarity	NPC476343
0.8992	High Similarity	NPC285289
0.896	High Similarity	NPC35932
0.896	High Similarity	NPC16208
0.896	High Similarity	NPC201587
0.896	High Similarity	NPC184447
0.896	High Similarity	NPC160991
0.896	High Similarity	NPC7903
0.896	High Similarity	NPC253105
0.8943	High Similarity	NPC154866
0.8934	High Similarity	NPC76451
0.8898	High Similarity	NPC24474
0.8898	High Similarity	NPC311595
0.8889	High Similarity	NPC132895
0.8889	High Similarity	NPC475840
0.8871	High Similarity	NPC3439
0.8871	High Similarity	NPC58164
0.8871	High Similarity	NPC10225
0.8871	High Similarity	NPC228769
0.8871	High Similarity	NPC226788
0.8871	High Similarity	NPC210623
0.8871	High Similarity	NPC285339
0.8871	High Similarity	NPC273295
0.8871	High Similarity	NPC218856
0.8871	High Similarity	NPC470633
0.8871	High Similarity	NPC202582
0.8871	High Similarity	NPC222004
0.8871	High Similarity	NPC470258
0.8871	High Similarity	NPC190629
0.887	High Similarity	NPC204120
0.8862	High Similarity	NPC474119
0.886	High Similarity	NPC156840
0.886	High Similarity	NPC8547
0.886	High Similarity	NPC257124
0.886	High Similarity	NPC173746
0.8852	High Similarity	NPC27352
0.8852	High Similarity	NPC105925
0.8843	High Similarity	NPC121115
0.8843	High Similarity	NPC471693
0.8839	High Similarity	NPC227894
0.8833	High Similarity	NPC310373
0.8833	High Similarity	NPC75713
0.8819	High Similarity	NPC287745
0.8819	High Similarity	NPC170694
0.8819	High Similarity	NPC310854
0.881	High Similarity	NPC470752
0.881	High Similarity	NPC470270
0.8803	High Similarity	NPC123948
0.88	High Similarity	NPC311680
0.88	High Similarity	NPC91291
0.88	High Similarity	NPC51840
0.88	High Similarity	NPC234488
0.88	High Similarity	NPC299221
0.88	High Similarity	NPC126836
0.879	High Similarity	NPC28765
0.8783	High Similarity	NPC280606
0.878	High Similarity	NPC223953
0.878	High Similarity	NPC473960
0.878	High Similarity	NPC112596
0.877	High Similarity	NPC122792
0.877	High Similarity	NPC228972
0.875	High Similarity	NPC472337
0.875	High Similarity	NPC164576
0.875	High Similarity	NPC256262
0.874	High Similarity	NPC158331
0.874	High Similarity	NPC229442
0.874	High Similarity	NPC168059
0.873	High Similarity	NPC309787
0.873	High Similarity	NPC469625
0.873	High Similarity	NPC469613
0.873	High Similarity	NPC30043
0.8729	High Similarity	NPC164386
0.872	High Similarity	NPC469963
0.872	High Similarity	NPC45824
0.872	High Similarity	NPC158477
0.872	High Similarity	NPC469951
0.871	High Similarity	NPC242032
0.871	High Similarity	NPC111247
0.871	High Similarity	NPC41706
0.871	High Similarity	NPC183181
0.871	High Similarity	NPC319625
0.871	High Similarity	NPC252131
0.871	High Similarity	NPC163332
0.871	High Similarity	NPC5428
0.871	High Similarity	NPC236760
0.871	High Similarity	NPC118533
0.871	High Similarity	NPC292056
0.871	High Similarity	NPC118787
0.871	High Similarity	NPC470699
0.871	High Similarity	NPC147821
0.871	High Similarity	NPC165045
0.8699	High Similarity	NPC148627
0.8699	High Similarity	NPC194519
0.8696	High Similarity	NPC296920
0.8696	High Similarity	NPC90520

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 NPC229401 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	313
0.1-0.2	956
0.2-0.3	2245
0.3-0.4	2710
0.4-0.5	1478
0.5-0.6	858
0.6-0.7	507
0.7-0.8	73
0.8-0.85	6
0.85-0.9	3
0.9-0.95	1
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.918	High Similarity	NPD3027	Phase 3
0.886	High Similarity	NPD228	Approved
0.8661	High Similarity	NPD1613	Approved
0.8661	High Similarity	NPD1612	Clinical (unspecified phase)
0.8492	Intermediate Similarity	NPD1529	Clinical (unspecified phase)
0.8413	Intermediate Similarity	NPD1530	Clinical (unspecified phase)
0.8387	Intermediate Similarity	NPD2983	Phase 2
0.8387	Intermediate Similarity	NPD2982	Phase 2
0.8306	Intermediate Similarity	NPD2981	Phase 2
0.813	Intermediate Similarity	NPD1357	Approved
0.8125	Intermediate Similarity	NPD3018	Phase 2
0.8095	Intermediate Similarity	NPD4379	Clinical (unspecified phase)
0.7903	Intermediate Similarity	NPD1548	Phase 1
0.7857	Intermediate Similarity	NPD9296	Approved
0.7846	Intermediate Similarity	NPD9494	Approved
0.7826	Intermediate Similarity	NPD1242	Phase 1
0.7817	Intermediate Similarity	NPD1653	Approved
0.7795	Intermediate Similarity	NPD1610	Phase 2
0.7787	Intermediate Similarity	NPD5283	Phase 1
0.7761	Intermediate Similarity	NPD230	Phase 1
0.7759	Intermediate Similarity	NPD291	Approved
0.7731	Intermediate Similarity	NPD290	Approved
0.7687	Intermediate Similarity	NPD1558	Phase 1
0.7667	Intermediate Similarity	NPD2684	Approved
0.7656	Intermediate Similarity	NPD3705	Approved
0.7652	Intermediate Similarity	NPD4908	Phase 1
0.7603	Intermediate Similarity	NPD1934	Approved
0.7561	Intermediate Similarity	NPD7843	Approved
0.7556	Intermediate Similarity	NPD3619	Clinical (unspecified phase)
0.7556	Intermediate Similarity	NPD3620	Phase 2
0.754	Intermediate Similarity	NPD5536	Phase 2
0.7537	Intermediate Similarity	NPD3145	Approved
0.7537	Intermediate Similarity	NPD4907	Clinical (unspecified phase)
0.7537	Intermediate Similarity	NPD3144	Approved
0.7535	Intermediate Similarity	NPD4357	Discontinued
0.752	Intermediate Similarity	NPD7157	Approved
0.7519	Intermediate Similarity	NPD422	Phase 1
0.7519	Intermediate Similarity	NPD1091	Approved
0.7518	Intermediate Similarity	NPD2219	Phase 1
0.75	Intermediate Similarity	NPD6917	Clinical (unspecified phase)
0.7482	Intermediate Similarity	NPD3540	Phase 1
0.7481	Intermediate Similarity	NPD2674	Phase 3
0.7459	Intermediate Similarity	NPD3022	Approved
0.7459	Intermediate Similarity	NPD3021	Approved
0.7458	Intermediate Similarity	NPD846	Approved
0.7458	Intermediate Similarity	NPD940	Approved
0.745	Intermediate Similarity	NPD3882	Suspended
0.7432	Intermediate Similarity	NPD2801	Approved
0.7413	Intermediate Similarity	NPD1511	Approved
0.741	Intermediate Similarity	NPD3539	Phase 1
0.7407	Intermediate Similarity	NPD6410	Clinical (unspecified phase)
0.7405	Intermediate Similarity	NPD4749	Approved
0.7376	Intermediate Similarity	NPD3060	Approved
0.7347	Intermediate Similarity	NPD4678	Approved
0.7347	Intermediate Similarity	NPD4675	Approved
0.7321	Intermediate Similarity	NPD9094	Approved
0.7315	Intermediate Similarity	NPD2393	Clinical (unspecified phase)
0.731	Intermediate Similarity	NPD1512	Approved
0.7295	Intermediate Similarity	NPD1358	Approved
0.7279	Intermediate Similarity	NPD4005	Discontinued
0.7273	Intermediate Similarity	NPD5307	Clinical (unspecified phase)
0.7266	Intermediate Similarity	NPD6111	Discontinued
0.7258	Intermediate Similarity	NPD9280	Clinical (unspecified phase)
0.7254	Intermediate Similarity	NPD4236	Phase 3
0.7254	Intermediate Similarity	NPD4237	Approved
0.7248	Intermediate Similarity	NPD37	Approved
0.7237	Intermediate Similarity	NPD6234	Discontinued
0.7234	Intermediate Similarity	NPD7266	Discontinued
0.7231	Intermediate Similarity	NPD9381	Approved
0.7231	Intermediate Similarity	NPD9384	Approved
0.7226	Intermediate Similarity	NPD6166	Phase 2
0.7226	Intermediate Similarity	NPD6168	Clinical (unspecified phase)
0.7226	Intermediate Similarity	NPD6167	Clinical (unspecified phase)
0.7213	Intermediate Similarity	NPD968	Approved
0.7206	Intermediate Similarity	NPD4625	Phase 3
0.7177	Intermediate Similarity	NPD556	Approved
0.7153	Intermediate Similarity	NPD6859	Clinical (unspecified phase)
0.7143	Intermediate Similarity	NPD9622	Approved
0.7133	Intermediate Similarity	NPD1652	Phase 2
0.713	Intermediate Similarity	NPD9365	Approved
0.7113	Intermediate Similarity	NPD1375	Discontinued
0.7105	Intermediate Similarity	NPD4868	Clinical (unspecified phase)
0.7105	Intermediate Similarity	NPD4966	Approved
0.7105	Intermediate Similarity	NPD4965	Approved
0.7105	Intermediate Similarity	NPD4967	Phase 2
0.7103	Intermediate Similarity	NPD7124	Phase 2
0.7101	Intermediate Similarity	NPD1726	Clinical (unspecified phase)
0.7092	Intermediate Similarity	NPD1510	Phase 2
0.709	Intermediate Similarity	NPD8651	Approved
0.7089	Intermediate Similarity	NPD7054	Approved
0.7068	Intermediate Similarity	NPD9269	Phase 2
0.7063	Intermediate Similarity	NPD970	Clinical (unspecified phase)
0.7059	Intermediate Similarity	NPD7975	Clinical (unspecified phase)
0.7059	Intermediate Similarity	NPD2861	Phase 2
0.7055	Intermediate Similarity	NPD5297	Approved
0.7054	Intermediate Similarity	NPD111	Approved
0.705	Intermediate Similarity	NPD4060	Phase 1
0.705	Intermediate Similarity	NPD1240	Approved
0.7044	Intermediate Similarity	NPD7074	Phase 3
0.7044	Intermediate Similarity	NPD7472	Approved
0.704	Intermediate Similarity	NPD4750	Phase 3
0.7039	Intermediate Similarity	NPD3817	Phase 2
0.7034	Intermediate Similarity	NPD6190	Approved
0.7032	Intermediate Similarity	NPD7199	Phase 2
0.7025	Intermediate Similarity	NPD7228	Approved
0.7025	Intermediate Similarity	NPD3818	Discontinued
0.7015	Intermediate Similarity	NPD3600	Clinical (unspecified phase)
0.7008	Intermediate Similarity	NPD9377	Approved
0.7008	Intermediate Similarity	NPD821	Approved
0.7008	Intermediate Similarity	NPD9379	Approved
0.7007	Intermediate Similarity	NPD4123	Phase 3
0.7	Intermediate Similarity	NPD1408	Clinical (unspecified phase)
0.7	Intermediate Similarity	NPD447	Suspended
0.6985	Remote Similarity	NPD9621	Approved
0.6985	Remote Similarity	NPD9619	Approved
0.6985	Remote Similarity	NPD9620	Approved
0.698	Remote Similarity	NPD3686	Approved
0.698	Remote Similarity	NPD3687	Approved
0.6977	Remote Similarity	NPD6671	Approved
0.6974	Remote Similarity	NPD2977	Approved
0.6974	Remote Similarity	NPD2978	Approved
0.697	Remote Similarity	NPD1778	Approved
0.6957	Remote Similarity	NPD3179	Approved
0.6957	Remote Similarity	NPD9295	Approved
0.6957	Remote Similarity	NPD3180	Approved
0.695	Remote Similarity	NPD1607	Approved
0.6947	Remote Similarity	NPD7534	Approved
0.6947	Remote Similarity	NPD7533	Approved
0.6939	Remote Similarity	NPD6143	Clinical (unspecified phase)
0.6935	Remote Similarity	NPD3134	Approved
0.6929	Remote Similarity	NPD2238	Phase 2
0.6929	Remote Similarity	NPD943	Approved
0.6928	Remote Similarity	NPD6374	Clinical (unspecified phase)
0.6913	Remote Similarity	NPD6980	Clinical (unspecified phase)
0.6901	Remote Similarity	NPD4538	Approved
0.6901	Remote Similarity	NPD4537	Clinical (unspecified phase)
0.6901	Remote Similarity	NPD4536	Approved
0.6899	Remote Similarity	NPD9299	Approved
0.6897	Remote Similarity	NPD5698	Clinical (unspecified phase)
0.6897	Remote Similarity	NPD4162	Approved
0.6897	Remote Similarity	NPD5177	Phase 3
0.6897	Remote Similarity	NPD6674	Discontinued
0.6894	Remote Similarity	NPD6797	Phase 2
0.6892	Remote Similarity	NPD1424	Approved
0.6887	Remote Similarity	NPD4380	Phase 2
0.6884	Remote Similarity	NPD5752	Clinical (unspecified phase)
0.6879	Remote Similarity	NPD5124	Phase 1
0.6879	Remote Similarity	NPD6232	Discontinued
0.6879	Remote Similarity	NPD5123	Clinical (unspecified phase)
0.6879	Remote Similarity	NPD4606	Clinical (unspecified phase)
0.6875	Remote Similarity	NPD1550	Clinical (unspecified phase)
0.6875	Remote Similarity	NPD1552	Clinical (unspecified phase)
0.6863	Remote Similarity	NPD1465	Phase 2
0.6861	Remote Similarity	NPD6584	Phase 3
0.6852	Remote Similarity	NPD7251	Discontinued
0.6849	Remote Similarity	NPD1878	Clinical (unspecified phase)
0.6846	Remote Similarity	NPD1940	Clinical (unspecified phase)
0.6842	Remote Similarity	NPD5090	Approved
0.6842	Remote Similarity	NPD5846	Approved
0.6842	Remote Similarity	NPD4626	Approved
0.6842	Remote Similarity	NPD5089	Approved
0.6842	Remote Similarity	NPD6516	Phase 2
0.6838	Remote Similarity	NPD2922	Phase 1
0.6835	Remote Similarity	NPD7184	Clinical (unspecified phase)
0.6831	Remote Similarity	NPD6653	Approved
0.6828	Remote Similarity	NPD1549	Phase 2
0.6824	Remote Similarity	NPD1774	Approved
0.6821	Remote Similarity	NPD6055	Clinical (unspecified phase)
0.6818	Remote Similarity	NPD9545	Approved
0.681	Remote Similarity	NPD7808	Phase 3
0.681	Remote Similarity	NPD4338	Clinical (unspecified phase)
0.6807	Remote Similarity	NPD2933	Approved
0.6807	Remote Similarity	NPD1432	Clinical (unspecified phase)
0.6807	Remote Similarity	NPD2934	Approved
0.6806	Remote Similarity	NPD1551	Phase 2
0.6806	Remote Similarity	NPD2161	Phase 2
0.6803	Remote Similarity	NPD5241	Discontinued
0.6803	Remote Similarity	NPD2677	Approved
0.6803	Remote Similarity	NPD302	Approved
0.6791	Remote Similarity	NPD3496	Discontinued
0.6786	Remote Similarity	NPD598	Approved
0.6786	Remote Similarity	NPD601	Approved
0.6786	Remote Similarity	NPD597	Approved
0.6786	Remote Similarity	NPD5111	Phase 2
0.6786	Remote Similarity	NPD9089	Approved
0.6786	Remote Similarity	NPD5110	Phase 2
0.6786	Remote Similarity	NPD5109	Approved
0.6779	Remote Similarity	NPD7447	Phase 1
0.677	Remote Similarity	NPD5844	Phase 1
0.6767	Remote Similarity	NPD9268	Approved
0.6763	Remote Similarity	NPD600	Approved
0.6763	Remote Similarity	NPD596	Approved
0.6761	Remote Similarity	NPD5735	Approved
0.6759	Remote Similarity	NPD2029	Clinical (unspecified phase)
0.6753	Remote Similarity	NPD5773	Approved
0.6753	Remote Similarity	NPD5772	Approved
0.675	Remote Similarity	NPD7473	Discontinued
0.675	Remote Similarity	NPD2859	Approved
0.675	Remote Similarity	NPD2860	Approved
0.675	Remote Similarity	NPD844	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