NPASS Compound

Structure

CID60538 OpenBabel06191715392D 22 24 0 0 1 0 0 0 0 0999 V2000 -2.5981 0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8660 -1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4641 3.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3301 1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3301 3.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1962 2.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0000 3.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8660 3.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5981 1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8660 1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8660 0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4641 2.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0000 2.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1962 3.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8660 1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7321 2.0000 0.0000 C 0 0 3 0 0 0 0 0 0 0 0 0 -0.8660 0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 -0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7321 3.0000 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 6.0622 3.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.7321 0.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 -1.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 21 1 0 0 0 0 2 22 1 0 0 0 0 3 5 1 0 0 0 0 3 12 2 0 0 0 0 4 6 2 0 0 0 0 4 12 1 0 0 0 0 5 14 2 0 0 0 0 6 14 1 0 0 0 0 7 8 1 0 0 0 0 7 13 1 0 0 0 0 8 19 1 0 0 0 0 9 12 1 0 0 0 0 9 16 1 0 0 0 0 10 13 2 0 0 0 0 10 17 1 0 0 0 0 11 15 2 0 0 0 0 11 18 1 0 0 0 0 13 15 1 0 0 0 0 14 20 1 0 0 0 0 15 16 1 0 0 0 0 16 19 1 0 0 0 0 17 18 2 0 0 0 0 17 21 1 0 0 0 0 18 22 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	145.05
Volume:	153.712
LogP:	1.535
LogD:	1.301
LogS:	-2.399
# Rotatable Bonds:	0
TPSA:	32.86
# H-Bond Aceptor:	2
# H-Bond Donor:	1
# Rings:	2
# Heavy Atoms:	2

MedChem Properties

QED Drug-Likeness Score:	0.599
Synthetic Accessibility Score:	1.665
Fsp3:	0.0
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:	-4.553
MDCK Permeability:	2.0078841771464795e-05
Pgp-inhibitor:	0.001
Pgp-substrate:	0.002
Human Intestinal Absorption (HIA):	0.008
20% Bioavailability (F20%):	0.107
30% Bioavailability (F30%):	0.336

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.554
Plasma Protein Binding (PPB):	72.01472473144531%
Volume Distribution (VD):	0.651
Pgp-substrate:	16.022981643676758%

ADMET: Metabolism

CYP1A2-inhibitor:	0.863
CYP1A2-substrate:	0.865
CYP2C19-inhibitor:	0.335
CYP2C19-substrate:	0.066
CYP2C9-inhibitor:	0.047
CYP2C9-substrate:	0.495
CYP2D6-inhibitor:	0.028
CYP2D6-substrate:	0.587
CYP3A4-inhibitor:	0.025
CYP3A4-substrate:	0.208

ADMET: Excretion

Clearance (CL):	6.864
Half-life (T1/2):	0.718

ADMET: Toxicity

hERG Blockers:	0.027
Human Hepatotoxicity (H-HT):	0.189
Drug-inuced Liver Injury (DILI):	0.949
AMES Toxicity:	0.638
Rat Oral Acute Toxicity:	0.543
Maximum Recommended Daily Dose:	0.127
Skin Sensitization:	0.745
Carcinogencity:	0.804
Eye Corrosion:	0.05
Eye Irritation:	0.955
Respiratory Toxicity:	0.96

Download Data

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

Natural Product: NPC60538

Natural Product ID:	NPC60538
*Common Name:**	4-[(6,7-Dimethoxy-1,2,3,4-Tetrahydroisoquinolin-1-Yl)Methyl]Phenol
IUPAC Name:	4-[(6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolin-1-yl)methyl]phenol
Synonyms:	DL-N-Norarmepavine
Standard InCHIKey:	NKBBUUNAVOMVER-UHFFFAOYSA-N
Standard InCHI:	InChI=1S/C18H21NO3/c1-21-17-10-13-7-8-19-16(15(13)11-18(17)22-2)9-12-3-5-14(20)6-4-12/h3-6,10-11,16,19-20H,7-9H2,1-2H3
SMILES:	COc1cc2CCNC(Cc3ccc(cc3)O)c2cc1OC
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL510363
PubChem CID:	317405
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0002566] Isoquinolines and derivatives [CHEMONTID:0000054] Benzylisoquinolines

*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
NPO10574	Machilus thunbergii	Species	Lauraceae	Eukaryota	n.a.	bark	n.a.	PMID[11045899]
NPO10574	Machilus thunbergii	Species	Lauraceae	Eukaryota	n.a.	bark	n.a.	PMID[19555186]
NPO3478	Nelumbo nucifera	Species	Nelumbonaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[19919095]
NPO3478	Nelumbo nucifera	Species	Nelumbonaceae	Eukaryota	flower buds and leaves	Khon Kaen province, Thailand	2010	PMID[23270663]
NPO3478	Nelumbo nucifera	Species	Nelumbonaceae	Eukaryota	Leaves	n.a.	n.a.	PMID[23642481]
NPO3478	Nelumbo nucifera	Species	Nelumbonaceae	Eukaryota	Flowers	n.a.	n.a.	PMID[26462418]
NPO3478	Nelumbo nucifera	Species	Nelumbonaceae	Eukaryota	Fruit	n.a.	n.a.	Database[FooDB]
NPO3478	Nelumbo nucifera	Species	Nelumbonaceae	Eukaryota	Rhizome	n.a.	n.a.	Database[FooDB]
NPO3478	Nelumbo nucifera	Species	Nelumbonaceae	Eukaryota	Seed	n.a.	n.a.	Database[FooDB]
NPO3478	Nelumbo nucifera	Species	Nelumbonaceae	Eukaryota		n.a.	n.a.	Database[FooDB]
NPO10574	Machilus thunbergii	Species	Lauraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO3478	Nelumbo nucifera	Species	Nelumbonaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO3478	Nelumbo nucifera	Species	Nelumbonaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO10574	Machilus thunbergii	Species	Lauraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO3478	Nelumbo nucifera	Species	Nelumbonaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO3478	Nelumbo nucifera	Species	Nelumbonaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO10574	Machilus thunbergii	Species	Lauraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO3478	Nelumbo nucifera	Species	Nelumbonaceae	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	5
Ki	1
Others	8
Potency	8

Activity Type	# Activity
CELL-LINE	4
Individual Protein	11
Others	3
Protein Family	1
Tissue	3

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT54	Individual Protein	Nonstructural protein 1	Influenza A virus	Potency	=	22387.2	nM	PMID[501435]
NPT56	Individual Protein	Beta-lactamase AmpC	Escherichia coli K-12	Potency	=	707.9	nM	PMID[501435]
NPT154	Individual Protein	Mothers against decapentaplegic homolog 3	Homo sapiens	Potency	n.a.	5623.4	nM	PMID[501435]
NPT10	Individual Protein	Geminin	Homo sapiens	Potency	n.a.	517.4	nM	PMID[501435]
NPT10	Individual Protein	Geminin	Homo sapiens	Potency	n.a.	20596.2	nM	PMID[501435]
NPT50	Individual Protein	Tyrosyl-DNA phosphodiesterase 1	Homo sapiens	Potency	n.a.	4610.9	nM	PMID[501435]
NPT66	Individual Protein	Acetylcholinesterase	Electrophorus electricus	IC50	>	100000.0	nM	PMID[501436]
NPT204	Individual Protein	Acetylcholinesterase	Homo sapiens	IC50	>	100000.0	nM	PMID[501436]
NPT439	Individual Protein	Butyrylcholinesterase	Homo sapiens	IC50	=	46770.0	nM	PMID[501436]
NPT20967	CELL-LINE	Platelet	n.a.	Activity	=	30.4	%	PMID[501433]
NPT20967	CELL-LINE	Platelet	n.a.	Activity	=	49.7	%	PMID[501433]
NPT20967	CELL-LINE	Platelet	n.a.	Activity	=	24.7	%	PMID[501433]
NPT20967	CELL-LINE	Platelet	n.a.	Activity	=	86.4	%	PMID[501433]
NPT177	Tissue	Aorta	Rattus norvegicus	Activity	=	107.8	%	PMID[501433]
NPT177	Tissue	Aorta	Rattus norvegicus	Activity	=	103.0	%	PMID[501433]
NPT177	Tissue	Aorta	Rattus norvegicus	Activity	=	95.7	%	PMID[501433]
NPT968	Protein Family	Adrenergic receptor alpha-1	Rattus norvegicus	Ki	=	5888.44	nM	PMID[501434]
NPT2	Others	Unspecified		IC50	>	50000.0	nM	PMID[501435]
NPT2	Others	Unspecified		Potency	n.a.	23109.3	nM	PMID[501435]
NPT2	Others	Unspecified		Potency	n.a.	32642.7	nM	PMID[501435]
NPT67	Individual Protein	Cholinesterase	Equus caballus	IC50	=	39700.0	nM	PMID[501436]
NPT78	Individual Protein	Beta amyloid A4 protein	Homo sapiens	Inhibition	=	36.0	%	PMID[501436]

☑ 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 NPC60538 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	256
0.1-0.2	1623
0.2-0.3	9723
0.3-0.4	8007
0.4-0.5	6669
0.5-0.6	11833
0.6-0.7	3551
0.7-0.8	709
0.8-0.85	166
0.85-0.9	114
0.9-0.95	38
0.95-1	8

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC207824
0.9859	High Similarity	NPC277669
0.9859	High Similarity	NPC76213
0.9586	High Similarity	NPC477564
0.9586	High Similarity	NPC2295
0.9574	High Similarity	NPC185838
0.9441	High Similarity	NPC191376
0.9441	High Similarity	NPC179825
0.9441	High Similarity	NPC321505
0.9375	High Similarity	NPC147390
0.9375	High Similarity	NPC246587
0.9375	High Similarity	NPC428
0.9375	High Similarity	NPC24233
0.9375	High Similarity	NPC135538
0.9375	High Similarity	NPC476571
0.9366	High Similarity	NPC294249
0.9306	High Similarity	NPC476151
0.922	High Similarity	NPC314682
0.9214	High Similarity	NPC253429
0.9178	High Similarity	NPC103379
0.9178	High Similarity	NPC477565
0.9155	High Similarity	NPC213206
0.9155	High Similarity	NPC188163
0.9155	High Similarity	NPC328750
0.9155	High Similarity	NPC474915
0.915	High Similarity	NPC35627
0.915	High Similarity	NPC476573
0.915	High Similarity	NPC81247
0.9116	High Similarity	NPC192768
0.9116	High Similarity	NPC97221
0.9116	High Similarity	NPC151895
0.9116	High Similarity	NPC88249
0.9116	High Similarity	NPC220858
0.9085	High Similarity	NPC121275
0.9085	High Similarity	NPC4138
0.9085	High Similarity	NPC284183
0.9014	High Similarity	NPC211468
0.9014	High Similarity	NPC219233
0.9014	High Similarity	NPC170170
0.9	High Similarity	NPC110416
0.9	High Similarity	NPC2413
0.9	High Similarity	NPC278799
0.9	High Similarity	NPC295691
0.9	High Similarity	NPC204828
0.9	High Similarity	NPC54379
0.9	High Similarity	NPC207757
0.9	High Similarity	NPC184026
0.9	High Similarity	NPC276588
0.9	High Similarity	NPC39701
0.9	High Similarity	NPC249797
0.9	High Similarity	NPC127674
0.9	High Similarity	NPC5238
0.9	High Similarity	NPC172765
0.9	High Similarity	NPC469817
0.9	High Similarity	NPC193949
0.9	High Similarity	NPC189266
0.8951	High Similarity	NPC323123
0.894	High Similarity	NPC126519
0.894	High Similarity	NPC203784
0.894	High Similarity	NPC170503
0.8929	High Similarity	NPC160692
0.8917	High Similarity	NPC475215
0.8917	High Similarity	NPC108434
0.8897	High Similarity	NPC476567
0.8897	High Similarity	NPC136860
0.8897	High Similarity	NPC128019
0.8874	High Similarity	NPC80129
0.8874	High Similarity	NPC187022
0.8861	High Similarity	NPC192135
0.8861	High Similarity	NPC66341
0.8861	High Similarity	NPC477020
0.8854	High Similarity	NPC69712
0.8854	High Similarity	NPC26240
0.8854	High Similarity	NPC109925
0.8854	High Similarity	NPC477562
0.8784	High Similarity	NPC476144
0.8784	High Similarity	NPC51957
0.8784	High Similarity	NPC106295
0.8784	High Similarity	NPC16107
0.8784	High Similarity	NPC210437
0.8766	High Similarity	NPC27410
0.8766	High Similarity	NPC166014
0.8742	High Similarity	NPC82285
0.8742	High Similarity	NPC133011
0.8741	High Similarity	NPC131204
0.8741	High Similarity	NPC301050
0.8734	High Similarity	NPC152212
0.8733	High Similarity	NPC274026
0.8725	High Similarity	NPC475959
0.8725	High Similarity	NPC7467
0.8701	High Similarity	NPC111485
0.8693	High Similarity	NPC147091
0.8654	High Similarity	NPC475393
0.8642	High Similarity	NPC474507
0.8636	High Similarity	NPC79328
0.8634	High Similarity	NPC173416
0.8634	High Similarity	NPC148709
0.8634	High Similarity	NPC476577
0.8618	High Similarity	NPC26601
0.8599	High Similarity	NPC232514
0.8599	High Similarity	NPC276944
0.8599	High Similarity	NPC238530
0.8592	High Similarity	NPC302171
0.8592	High Similarity	NPC300020
0.8592	High Similarity	NPC33338
0.8582	High Similarity	NPC160193
0.8571	High Similarity	NPC477558
0.8553	High Similarity	NPC81733
0.8553	High Similarity	NPC326316
0.8544	High Similarity	NPC86144
0.8544	High Similarity	NPC13916
0.8544	High Similarity	NPC304659
0.8544	High Similarity	NPC240841
0.8544	High Similarity	NPC42549
0.8544	High Similarity	NPC317272
0.8544	High Similarity	NPC256012
0.8544	High Similarity	NPC250846
0.8544	High Similarity	NPC264850
0.8544	High Similarity	NPC268503
0.8535	High Similarity	NPC324144
0.8523	High Similarity	NPC130926
0.8497	Intermediate Similarity	NPC37272
0.8491	Intermediate Similarity	NPC12053
0.8491	Intermediate Similarity	NPC474931
0.8491	Intermediate Similarity	NPC306555
0.8491	Intermediate Similarity	NPC145832
0.8491	Intermediate Similarity	NPC158376
0.8491	Intermediate Similarity	NPC298979
0.8491	Intermediate Similarity	NPC81218
0.8491	Intermediate Similarity	NPC117188
0.8491	Intermediate Similarity	NPC205421
0.8485	Intermediate Similarity	NPC135772
0.8481	Intermediate Similarity	NPC13504
0.8481	Intermediate Similarity	NPC306843
0.8481	Intermediate Similarity	NPC136508
0.8481	Intermediate Similarity	NPC196447
0.8481	Intermediate Similarity	NPC253043
0.8481	Intermediate Similarity	NPC96603
0.8481	Intermediate Similarity	NPC134858
0.8481	Intermediate Similarity	NPC24465
0.8481	Intermediate Similarity	NPC477563
0.8481	Intermediate Similarity	NPC78222
0.8481	Intermediate Similarity	NPC212794
0.8476	Intermediate Similarity	NPC155442
0.8476	Intermediate Similarity	NPC477561
0.8476	Intermediate Similarity	NPC312918
0.8476	Intermediate Similarity	NPC476574
0.8452	Intermediate Similarity	NPC29647
0.8452	Intermediate Similarity	NPC186063
0.844	Intermediate Similarity	NPC172403
0.8438	Intermediate Similarity	NPC83198
0.8438	Intermediate Similarity	NPC204908
0.8431	Intermediate Similarity	NPC476568
0.8425	Intermediate Similarity	NPC193528
0.8421	Intermediate Similarity	NPC219162
0.8421	Intermediate Similarity	NPC92541
0.8418	Intermediate Similarity	NPC233650
0.8418	Intermediate Similarity	NPC189470
0.8418	Intermediate Similarity	NPC1229
0.8408	Intermediate Similarity	NPC249274
0.8408	Intermediate Similarity	NPC205167
0.8387	Intermediate Similarity	NPC41178
0.8387	Intermediate Similarity	NPC216459
0.8387	Intermediate Similarity	NPC138487
0.8377	Intermediate Similarity	NPC210148
0.8377	Intermediate Similarity	NPC233029
0.8375	Intermediate Similarity	NPC204947
0.8375	Intermediate Similarity	NPC210140
0.8365	Intermediate Similarity	NPC209377
0.8365	Intermediate Similarity	NPC2770
0.8365	Intermediate Similarity	NPC39103
0.8354	Intermediate Similarity	NPC60186
0.8344	Intermediate Similarity	NPC59028
0.8344	Intermediate Similarity	NPC92191
0.8333	Intermediate Similarity	NPC37205
0.8333	Intermediate Similarity	NPC247639
0.8333	Intermediate Similarity	NPC25084
0.8333	Intermediate Similarity	NPC146288
0.8333	Intermediate Similarity	NPC160931
0.8323	Intermediate Similarity	NPC66573
0.8313	Intermediate Similarity	NPC195392
0.8313	Intermediate Similarity	NPC56887
0.8313	Intermediate Similarity	NPC223077
0.8313	Intermediate Similarity	NPC193853
0.8291	Intermediate Similarity	NPC97072
0.8291	Intermediate Similarity	NPC215829
0.8289	Intermediate Similarity	NPC95075
0.8289	Intermediate Similarity	NPC144863
0.8289	Intermediate Similarity	NPC253883
0.8289	Intermediate Similarity	NPC90844
0.8286	Intermediate Similarity	NPC217277
0.8284	Intermediate Similarity	NPC11296
0.8284	Intermediate Similarity	NPC48490
0.8284	Intermediate Similarity	NPC175890
0.8284	Intermediate Similarity	NPC274661
0.8284	Intermediate Similarity	NPC82457
0.8282	Intermediate Similarity	NPC232386
0.8282	Intermediate Similarity	NPC152680
0.8282	Intermediate Similarity	NPC190783
0.828	Intermediate Similarity	NPC476572

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 NPC60538 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	168
0.1-0.2	704
0.2-0.3	1081
0.3-0.4	1588
0.4-0.5	2688
0.5-0.6	1913
0.6-0.7	726
0.7-0.8	247
0.8-0.85	26
0.85-0.9	8
0.9-0.95	1
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.9155	High Similarity	NPD4664	Clinical (unspecified phase)
0.8919	High Similarity	NPD6031	Approved
0.8919	High Similarity	NPD6030	Approved
0.8874	High Similarity	NPD7298	Approved
0.8784	High Similarity	NPD4584	Approved
0.8649	High Similarity	NPD3845	Phase 1
0.8553	High Similarity	NPD4017	Approved
0.8523	High Similarity	NPD2422	Clinical (unspecified phase)
0.8456	Intermediate Similarity	NPD5241	Discontinued
0.8446	Intermediate Similarity	NPD3060	Approved
0.8442	Intermediate Similarity	NPD4772	Phase 2
0.8442	Intermediate Similarity	NPD4773	Phase 2
0.8428	Intermediate Similarity	NPD4010	Discontinued
0.8418	Intermediate Similarity	NPD7201	Clinical (unspecified phase)
0.8405	Intermediate Similarity	NPD6297	Approved
0.8367	Intermediate Similarity	NPD1632	Clinical (unspecified phase)
0.8301	Intermediate Similarity	NPD3640	Phase 3
0.8301	Intermediate Similarity	NPD3641	Approved
0.8301	Intermediate Similarity	NPD3639	Approved
0.8217	Intermediate Similarity	NPD6818	Clinical (unspecified phase)
0.821	Intermediate Similarity	NPD2898	Approved
0.8204	Intermediate Similarity	NPD6853	Approved
0.8204	Intermediate Similarity	NPD6851	Approved
0.8176	Intermediate Similarity	NPD7833	Phase 2
0.8176	Intermediate Similarity	NPD7831	Phase 2
0.8176	Intermediate Similarity	NPD7832	Clinical (unspecified phase)
0.8169	Intermediate Similarity	NPD3055	Approved
0.8169	Intermediate Similarity	NPD3053	Approved
0.8138	Intermediate Similarity	NPD5718	Phase 2
0.8137	Intermediate Similarity	NPD6107	Approved
0.8101	Intermediate Similarity	NPD2977	Approved
0.8101	Intermediate Similarity	NPD2978	Approved
0.8086	Intermediate Similarity	NPD4166	Phase 2
0.8079	Intermediate Similarity	NPD4162	Approved
0.8069	Intermediate Similarity	NPD2669	Clinical (unspecified phase)
0.8052	Intermediate Similarity	NPD1754	Clinical (unspecified phase)
0.8014	Intermediate Similarity	NPD2028	Clinical (unspecified phase)
0.8	Intermediate Similarity	NPD4581	Clinical (unspecified phase)
0.7988	Intermediate Similarity	NPD8054	Approved
0.7988	Intermediate Similarity	NPD8053	Approved
0.7987	Intermediate Similarity	NPD2420	Approved
0.7987	Intermediate Similarity	NPD2421	Approved
0.7959	Intermediate Similarity	NPD554	Clinical (unspecified phase)
0.7959	Intermediate Similarity	NPD2674	Phase 3
0.7935	Intermediate Similarity	NPD1424	Approved
0.7933	Intermediate Similarity	NPD6029	Clinical (unspecified phase)
0.7933	Intermediate Similarity	NPD6028	Clinical (unspecified phase)
0.7908	Intermediate Similarity	NPD3977	Clinical (unspecified phase)
0.7885	Intermediate Similarity	NPD3647	Clinical (unspecified phase)
0.7879	Intermediate Similarity	NPD27	Approved
0.7879	Intermediate Similarity	NPD2489	Approved
0.7877	Intermediate Similarity	NPD5752	Clinical (unspecified phase)
0.7866	Intermediate Similarity	NPD6071	Discontinued
0.7847	Intermediate Similarity	NPD5310	Approved
0.7847	Intermediate Similarity	NPD5311	Approved
0.7843	Intermediate Similarity	NPD5177	Phase 3
0.7831	Intermediate Similarity	NPD5602	Clinical (unspecified phase)
0.7826	Intermediate Similarity	NPD2563	Approved
0.7826	Intermediate Similarity	NPD2560	Approved
0.7818	Intermediate Similarity	NPD2970	Approved
0.7818	Intermediate Similarity	NPD2969	Approved
0.7818	Intermediate Similarity	NPD4083	Discontinued
0.78	Intermediate Similarity	NPD823	Approved
0.78	Intermediate Similarity	NPD817	Approved
0.7784	Intermediate Similarity	NPD8251	Approved
0.7784	Intermediate Similarity	NPD8252	Approved
0.7784	Intermediate Similarity	NPD8099	Discontinued
0.7778	Intermediate Similarity	NPD7153	Discontinued
0.7778	Intermediate Similarity	NPD6788	Approved
0.777	Intermediate Similarity	NPD3144	Approved
0.777	Intermediate Similarity	NPD3145	Approved
0.7765	Intermediate Similarity	NPD8453	Clinical (unspecified phase)
0.7758	Intermediate Similarity	NPD3051	Approved
0.7756	Intermediate Similarity	NPD3124	Discontinued
0.7748	Intermediate Similarity	NPD6895	Approved
0.7748	Intermediate Similarity	NPD6896	Approved
0.7742	Intermediate Similarity	NPD5160	Discontinued
0.7738	Intermediate Similarity	NPD8156	Discontinued
0.7727	Intermediate Similarity	NPD2458	Approved
0.7727	Intermediate Similarity	NPD2460	Phase 3
0.7727	Intermediate Similarity	NPD2459	Approved
0.7718	Intermediate Similarity	NPD3531	Approved
0.7718	Intermediate Similarity	NPD3532	Approved
0.7718	Intermediate Similarity	NPD3530	Approved
0.7712	Intermediate Similarity	NPD2029	Clinical (unspecified phase)
0.7707	Intermediate Similarity	NPD2874	Phase 2
0.7702	Intermediate Similarity	NPD5720	Discontinued
0.7697	Intermediate Similarity	NPD7802	Discontinued
0.7697	Intermediate Similarity	NPD1753	Discontinued
0.7692	Intermediate Similarity	NPD7479	Phase 2
0.7682	Intermediate Similarity	NPD2989	Phase 2
0.7682	Intermediate Similarity	NPD2986	Phase 2
0.7682	Intermediate Similarity	NPD3054	Approved
0.7682	Intermediate Similarity	NPD3052	Approved
0.7679	Intermediate Similarity	NPD5708	Clinical (unspecified phase)
0.7643	Intermediate Similarity	NPD7598	Phase 2
0.763	Intermediate Similarity	NPD5087	Clinical (unspecified phase)
0.7628	Intermediate Similarity	NPD5084	Clinical (unspecified phase)
0.7625	Intermediate Similarity	NPD7261	Clinical (unspecified phase)
0.761	Intermediate Similarity	NPD5976	Discontinued
0.7607	Intermediate Similarity	NPD5977	Approved
0.7607	Intermediate Similarity	NPD5978	Approved
0.76	Intermediate Similarity	NPD1130	Approved
0.76	Intermediate Similarity	NPD1132	Approved
0.76	Intermediate Similarity	NPD1136	Approved
0.7595	Intermediate Similarity	NPD1771	Clinical (unspecified phase)
0.7582	Intermediate Similarity	NPD2156	Approved
0.7582	Intermediate Similarity	NPD2155	Approved
0.7582	Intermediate Similarity	NPD2154	Approved
0.758	Intermediate Similarity	NPD6783	Clinical (unspecified phase)
0.7576	Intermediate Similarity	NPD5709	Phase 3
0.7572	Intermediate Similarity	NPD6618	Phase 2
0.7566	Intermediate Similarity	NPD2653	Approved
0.755	Intermediate Similarity	NPD3059	Approved
0.755	Intermediate Similarity	NPD3110	Approved
0.755	Intermediate Similarity	NPD3062	Approved
0.755	Intermediate Similarity	NPD3061	Approved
0.755	Intermediate Similarity	NPD3109	Approved
0.7548	Intermediate Similarity	NPD7045	Clinical (unspecified phase)
0.7547	Intermediate Similarity	NPD5261	Clinical (unspecified phase)
0.7533	Intermediate Similarity	NPD597	Approved
0.7533	Intermediate Similarity	NPD601	Approved
0.7533	Intermediate Similarity	NPD3056	Clinical (unspecified phase)
0.7533	Intermediate Similarity	NPD598	Approved
0.753	Intermediate Similarity	NPD4666	Phase 3
0.7516	Intermediate Similarity	NPD5307	Clinical (unspecified phase)
0.7516	Intermediate Similarity	NPD4005	Discontinued
0.7515	Intermediate Similarity	NPD4055	Discovery
0.75	Intermediate Similarity	NPD2668	Approved
0.75	Intermediate Similarity	NPD4727	Phase 1
0.75	Intermediate Similarity	NPD2667	Approved
0.7483	Intermediate Similarity	NPD4475	Approved
0.7483	Intermediate Similarity	NPD4474	Approved
0.7468	Intermediate Similarity	NPD2120	Phase 2
0.7466	Intermediate Similarity	NPD2232	Approved
0.7466	Intermediate Similarity	NPD2230	Approved
0.7466	Intermediate Similarity	NPD2233	Approved
0.7457	Intermediate Similarity	NPD3936	Clinical (unspecified phase)
0.7453	Intermediate Similarity	NPD3687	Approved
0.7453	Intermediate Similarity	NPD3686	Approved
0.7452	Intermediate Similarity	NPD6331	Phase 2
0.7452	Intermediate Similarity	NPD6658	Clinical (unspecified phase)
0.7451	Intermediate Similarity	NPD5314	Approved
0.745	Intermediate Similarity	NPD3635	Approved
0.745	Intermediate Similarity	NPD3636	Approved
0.745	Intermediate Similarity	NPD3637	Approved
0.7443	Intermediate Similarity	NPD7906	Approved
0.7439	Intermediate Similarity	NPD4585	Approved
0.7438	Intermediate Similarity	NPD7527	Clinical (unspecified phase)
0.7438	Intermediate Similarity	NPD7526	Approved
0.7438	Intermediate Similarity	NPD52	Approved
0.7436	Intermediate Similarity	NPD4256	Phase 2
0.7436	Intermediate Similarity	NPD4257	Approved
0.7431	Intermediate Similarity	NPD4093	Discontinued
0.7427	Intermediate Similarity	NPD4873	Discontinued
0.7427	Intermediate Similarity	NPD5312	Approved
0.7427	Intermediate Similarity	NPD5313	Approved
0.7427	Intermediate Similarity	NPD5096	Phase 3
0.7427	Intermediate Similarity	NPD6042	Phase 2
0.7427	Intermediate Similarity	NPD5095	Phase 3
0.7427	Intermediate Similarity	NPD42	Phase 2
0.7423	Intermediate Similarity	NPD7109	Clinical (unspecified phase)
0.7423	Intermediate Similarity	NPD7110	Phase 1
0.7419	Intermediate Similarity	NPD3156	Discontinued
0.7415	Intermediate Similarity	NPD1669	Approved
0.7414	Intermediate Similarity	NPD7313	Approved
0.7414	Intermediate Similarity	NPD7310	Approved
0.7414	Intermediate Similarity	NPD4578	Approved
0.7414	Intermediate Similarity	NPD7312	Approved
0.7414	Intermediate Similarity	NPD3534	Clinical (unspecified phase)
0.7414	Intermediate Similarity	NPD7311	Approved
0.7414	Intermediate Similarity	NPD4577	Approved
0.7405	Intermediate Similarity	NPD3692	Discontinued
0.7405	Intermediate Similarity	NPD2677	Approved
0.7389	Intermediate Similarity	NPD4237	Approved
0.7389	Intermediate Similarity	NPD7667	Clinical (unspecified phase)
0.7389	Intermediate Similarity	NPD4236	Phase 3
0.7375	Intermediate Similarity	NPD4123	Phase 3
0.7375	Intermediate Similarity	NPD3536	Discontinued
0.7375	Intermediate Similarity	NPD3645	Discontinued
0.7371	Intermediate Similarity	NPD7309	Approved
0.736	Intermediate Similarity	NPD5525	Clinical (unspecified phase)
0.7358	Intermediate Similarity	NPD7124	Phase 2
0.7353	Intermediate Similarity	NPD4481	Phase 3
0.7351	Intermediate Similarity	NPD5156	Approved
0.7351	Intermediate Similarity	NPD5155	Approved
0.7347	Intermediate Similarity	NPD2562	Approved
0.7347	Intermediate Similarity	NPD2561	Approved
0.7338	Intermediate Similarity	NPD2568	Approved
0.7338	Intermediate Similarity	NPD4579	Clinical (unspecified phase)
0.7329	Intermediate Similarity	NPD2688	Clinical (unspecified phase)
0.7329	Intermediate Similarity	NPD6090	Discontinued
0.7326	Intermediate Similarity	NPD3933	Discontinued
0.7325	Intermediate Similarity	NPD1372	Clinical (unspecified phase)
0.7324	Intermediate Similarity	NPD593	Approved
0.7324	Intermediate Similarity	NPD595	Approved
0.7322	Intermediate Similarity	NPD6612	Phase 2
0.732	Intermediate Similarity	NPD2238	Phase 2
0.7314	Intermediate Similarity	NPD7281	Phase 3
0.7314	Intermediate Similarity	NPD7280	Phase 3

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