NPASS Compound

Structure

CID251855 OpenBabel06191716052D 23 24 0 0 0 0 0 0 0 0999 V2000 -6.9282 4.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3301 4.5000 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 1.7321 1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4641 1.0000 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 -5.1962 1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0622 1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3301 2.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7321 -0.0000 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 -4.3301 1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7321 1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0622 2.5000 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 -0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0000 1.0000 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 0.8660 -0.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.9282 3.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.1962 4.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.8660 -1.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.8660 1.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 20 1 0 0 0 0 2 21 1 0 0 0 0 3 22 1 0 0 0 0 4 23 1 0 0 0 0 5 6 1 0 0 0 0 5 12 1 0 0 0 0 6 13 1 0 0 0 0 7 8 2 0 0 0 0 7 12 1 0 0 0 0 8 14 1 0 0 0 0 9 12 2 0 0 0 0 9 15 1 0 0 0 0 10 13 2 0 0 0 0 10 16 1 0 0 0 0 11 13 1 0 0 0 0 11 17 2 0 0 0 0 14 15 2 0 0 0 0 14 20 1 0 0 0 0 15 21 1 0 0 0 0 16 18 2 0 0 0 0 16 22 1 0 0 0 0 17 18 1 0 0 0 0 17 23 1 0 0 0 0 18 19 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	318.15
Volume:	330.904
LogP:	2.799
LogD:	3.295
LogS:	-3.889
# Rotatable Bonds:	7
TPSA:	57.15
# H-Bond Aceptor:	5
# H-Bond Donor:	1
# Rings:	2
# Heavy Atoms:	5

MedChem Properties

QED Drug-Likeness Score:	0.849
Synthetic Accessibility Score:	1.863
Fsp3:	0.333
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:	-4.795
MDCK Permeability:	2.532946200517472e-05
Pgp-inhibitor:	0.99
Pgp-substrate:	0.944
Human Intestinal Absorption (HIA):	0.003
20% Bioavailability (F20%):	0.176
30% Bioavailability (F30%):	0.406

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.049
Plasma Protein Binding (PPB):	87.8423080444336%
Volume Distribution (VD):	0.676
Pgp-substrate:	5.352849006652832%

ADMET: Metabolism

CYP1A2-inhibitor:	0.82
CYP1A2-substrate:	0.963
CYP2C19-inhibitor:	0.803
CYP2C19-substrate:	0.916
CYP2C9-inhibitor:	0.653
CYP2C9-substrate:	0.861
CYP2D6-inhibitor:	0.359
CYP2D6-substrate:	0.944
CYP3A4-inhibitor:	0.863
CYP3A4-substrate:	0.729

ADMET: Excretion

Clearance (CL):	11.699
Half-life (T1/2):	0.866

ADMET: Toxicity

hERG Blockers:	0.15
Human Hepatotoxicity (H-HT):	0.11
Drug-inuced Liver Injury (DILI):	0.481
AMES Toxicity:	0.029
Rat Oral Acute Toxicity:	0.014
Maximum Recommended Daily Dose:	0.136
Skin Sensitization:	0.941
Carcinogencity:	0.047
Eye Corrosion:	0.034
Eye Irritation:	0.283
Respiratory Toxicity:	0.133

Download Data

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

Natural Product: NPC251855

Natural Product ID:	NPC251855
*Common Name:**	4-(3,4-Dimethoxyphenethyl)-2,6-Dimethoxyphenol
IUPAC Name:	4-[2-(3,4-dimethoxyphenyl)ethyl]-2,6-dimethoxyphenol
Synonyms:
Standard InCHIKey:	YUHRVKGYFHPWRI-UHFFFAOYSA-N
Standard InCHI:	InChI=1S/C18H22O5/c1-20-14-8-7-12(9-15(14)21-2)5-6-13-10-16(22-3)18(19)17(11-13)23-4/h7-11,19H,5-6H2,1-4H3
SMILES:	COc1cc(CCc2cc(OC)c(c(c2)OC)O)ccc1OC
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL219352
PubChem CID:	5315860
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000253] Stilbenes

*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
NPO3894	Dendrobium nobile	Species	Orchidaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[11575955]
NPO8966	Callophycus serratus	Species	Solieriaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[16268553]
NPO8966	Callophycus serratus	Species	Solieriaceae	Eukaryota	n.a.	Fijian red alga	n.a.	PMID[16724831]
NPO3894	Dendrobium nobile	Species	Orchidaceae	Eukaryota	stems	Yunnan Province, China	2004	PMID[17253844]
NPO8966	Callophycus serratus	Species	Solieriaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[17715978]
NPO3894	Dendrobium nobile	Species	Orchidaceae	Eukaryota	Stems	purchased from Kyoungdong Oriental Herbal Market, Seoul, Korea	2006-APR	PMID[18052323]
NPO8966	Callophycus serratus	Species	Solieriaceae	Eukaryota	n.a.	Fijian red alga	n.a.	PMID[20141173]
NPO3894	Dendrobium nobile	Species	Orchidaceae	Eukaryota	Stems	n.a.	n.a.	PMID[27310249]
NPO8966	Callophycus serratus	Species	Solieriaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[30407005]
NPO5019	Mespilus germanica	Species	Rosaceae	Eukaryota		n.a.	n.a.	Database[FooDB]
NPO20900	Dendrobium chrysotoxum	Species	Orchidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO3894	Dendrobium nobile	Species	Orchidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO5019	Mespilus germanica	Species	Rosaceae	Eukaryota	Fruits	n.a.		Database[Phenol-Explorer]
NPO3894	Dendrobium nobile	Species	Orchidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO20900	Dendrobium chrysotoxum	Species	Orchidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO11242	Gynochthodes parvifolia	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO18039	Herba dendrobii	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[TCMID]
NPO3894	Dendrobium nobile	Species	Orchidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO20900	Dendrobium chrysotoxum	Species	Orchidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO3894	Dendrobium nobile	Species	Orchidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO15662	Ligustrum ovalifolium	Species	Oleaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO11242	Gynochthodes parvifolia	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO4581	Ungernia victoris	Species	Amaryllidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO15280	Sideritis grandiflora	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO5019	Mespilus germanica	Species	Rosaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO1575	Mikania luetzelburgii	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO6178	Solanum euacanthum	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO8966	Callophycus serratus	Species	Solieriaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO13053	Corydalis conspersa	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO3894	Dendrobium nobile	Species	Orchidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO20900	Dendrobium chrysotoxum	Species	Orchidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO326	Pittosporum brevicalyx	Species	Pittosporaceae	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	1

Activity Type	# Activity
Others	1

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT1	Others	Radical scavenging activity		IC50	=	14000.0	nM	PMID[525596]

☑ 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 NPC251855 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	381
0.1-0.2	1734
0.2-0.3	5470
0.3-0.4	13470
0.4-0.5	3864
0.5-0.6	4350
0.6-0.7	7288
0.7-0.8	4502
0.8-0.85	849
0.85-0.9	483
0.9-0.95	235
0.95-1	71

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC208950
1.0	High Similarity	NPC298757
1.0	High Similarity	NPC221077
1.0	High Similarity	NPC233410
1.0	High Similarity	NPC117214
1.0	High Similarity	NPC193544
1.0	High Similarity	NPC475169
1.0	High Similarity	NPC17943
1.0	High Similarity	NPC472093
1.0	High Similarity	NPC203133
1.0	High Similarity	NPC116907
1.0	High Similarity	NPC57490
0.9833	High Similarity	NPC169474
0.9833	High Similarity	NPC159968
0.9833	High Similarity	NPC74817
0.9833	High Similarity	NPC124452
0.9833	High Similarity	NPC236791
0.9833	High Similarity	NPC246620
0.9833	High Similarity	NPC293054
0.9833	High Similarity	NPC282000
0.9833	High Similarity	NPC127587
0.9833	High Similarity	NPC82679
0.9833	High Similarity	NPC324112
0.9831	High Similarity	NPC233526
0.9831	High Similarity	NPC197757
0.9831	High Similarity	NPC282496
0.9831	High Similarity	NPC228922
0.9831	High Similarity	NPC136319
0.9752	High Similarity	NPC186843
0.9752	High Similarity	NPC470213
0.9752	High Similarity	NPC98631
0.9752	High Similarity	NPC206615
0.975	High Similarity	NPC18924
0.975	High Similarity	NPC78974
0.975	High Similarity	NPC214406
0.975	High Similarity	NPC103823
0.975	High Similarity	NPC28730
0.975	High Similarity	NPC44748
0.975	High Similarity	NPC76451
0.975	High Similarity	NPC223136
0.9746	High Similarity	NPC71579
0.9746	High Similarity	NPC262253
0.9746	High Similarity	NPC473411
0.9746	High Similarity	NPC41562
0.9672	High Similarity	NPC476968
0.9672	High Similarity	NPC170844
0.9669	High Similarity	NPC210355
0.9667	High Similarity	NPC265483
0.9667	High Similarity	NPC82483
0.9667	High Similarity	NPC234400
0.9667	High Similarity	NPC105925
0.9667	High Similarity	NPC299584
0.9667	High Similarity	NPC60885
0.9593	High Similarity	NPC234488
0.9593	High Similarity	NPC311680
0.9593	High Similarity	NPC299221
0.9593	High Similarity	NPC126836
0.9593	High Similarity	NPC51840
0.959	High Similarity	NPC28765
0.959	High Similarity	NPC154866
0.9583	High Similarity	NPC206487
0.9583	High Similarity	NPC5796
0.9576	High Similarity	NPC166759
0.9516	High Similarity	NPC474017
0.9512	High Similarity	NPC212015
0.9512	High Similarity	NPC58164
0.9512	High Similarity	NPC10225
0.9508	High Similarity	NPC252131
0.9508	High Similarity	NPC266555
0.9508	High Similarity	NPC470699
0.9508	High Similarity	NPC236760
0.95	High Similarity	NPC95168
0.95	High Similarity	NPC84086
0.95	High Similarity	NPC121115
0.9492	High Similarity	NPC474565
0.9492	High Similarity	NPC232084
0.9492	High Similarity	NPC247364
0.9492	High Similarity	NPC61516
0.9492	High Similarity	NPC10932
0.944	High Similarity	NPC201587
0.944	High Similarity	NPC6451
0.944	High Similarity	NPC253105
0.9435	High Similarity	NPC472338
0.9431	High Similarity	NPC266691
0.9426	High Similarity	NPC223953
0.9426	High Similarity	NPC181361
0.9421	High Similarity	NPC122792
0.9421	High Similarity	NPC228972
0.9407	High Similarity	NPC20674
0.9407	High Similarity	NPC475961
0.9407	High Similarity	NPC254625
0.9407	High Similarity	NPC226629
0.9365	High Similarity	NPC475840
0.9365	High Similarity	NPC158331
0.9365	High Similarity	NPC32778
0.936	High Similarity	NPC470096
0.936	High Similarity	NPC12275
0.936	High Similarity	NPC232275
0.936	High Similarity	NPC472597
0.936	High Similarity	NPC474356
0.936	High Similarity	NPC470095
0.936	High Similarity	NPC45715
0.9339	High Similarity	NPC471693
0.9333	High Similarity	NPC49341
0.9333	High Similarity	NPC75713
0.9322	High Similarity	NPC470626
0.9291	High Similarity	NPC317380
0.9291	High Similarity	NPC287745
0.9286	High Similarity	NPC160991
0.9286	High Similarity	NPC175067
0.9286	High Similarity	NPC16208
0.9286	High Similarity	NPC202762
0.9286	High Similarity	NPC184447
0.9286	High Similarity	NPC7903
0.9286	High Similarity	NPC204215
0.9286	High Similarity	NPC14224
0.9286	High Similarity	NPC127624
0.9286	High Similarity	NPC35932
0.9286	High Similarity	NPC86655
0.9286	High Similarity	NPC161958
0.9286	High Similarity	NPC470752
0.928	High Similarity	NPC192687
0.928	High Similarity	NPC224157
0.928	High Similarity	NPC63574
0.9237	High Similarity	NPC474933
0.9237	High Similarity	NPC259638
0.9237	High Similarity	NPC293619
0.9219	High Similarity	NPC10314
0.9219	High Similarity	NPC99572
0.9219	High Similarity	NPC474206
0.9219	High Similarity	NPC158142
0.9219	High Similarity	NPC94750
0.9219	High Similarity	NPC200557
0.9219	High Similarity	NPC69029
0.9219	High Similarity	NPC121812
0.9219	High Similarity	NPC313081
0.9219	High Similarity	NPC108198
0.9219	High Similarity	NPC112246
0.9219	High Similarity	NPC126409
0.9219	High Similarity	NPC256262
0.9219	High Similarity	NPC294884
0.9219	High Similarity	NPC112939
0.9219	High Similarity	NPC470356
0.9213	High Similarity	NPC229442
0.9213	High Similarity	NPC471390
0.9213	High Similarity	NPC168059
0.9213	High Similarity	NPC471391
0.9206	High Similarity	NPC15543
0.9206	High Similarity	NPC309787
0.92	High Similarity	NPC226788
0.92	High Similarity	NPC470633
0.92	High Similarity	NPC202582
0.92	High Similarity	NPC218856
0.92	High Similarity	NPC210623
0.92	High Similarity	NPC3439
0.92	High Similarity	NPC190629
0.92	High Similarity	NPC469963
0.92	High Similarity	NPC228769
0.92	High Similarity	NPC469951
0.92	High Similarity	NPC190144
0.92	High Similarity	NPC285339
0.92	High Similarity	NPC470258
0.92	High Similarity	NPC273295
0.92	High Similarity	NPC222004
0.9194	High Similarity	NPC5428
0.9194	High Similarity	NPC165045
0.9194	High Similarity	NPC474119
0.9194	High Similarity	NPC118533
0.9194	High Similarity	NPC242032
0.9187	High Similarity	NPC148627
0.918	High Similarity	NPC220598
0.918	High Similarity	NPC165375
0.9174	High Similarity	NPC477886
0.9174	High Similarity	NPC312675
0.9174	High Similarity	NPC184651
0.9174	High Similarity	NPC324571
0.9174	High Similarity	NPC54872
0.9174	High Similarity	NPC145780
0.9174	High Similarity	NPC470212
0.9174	High Similarity	NPC473853
0.9174	High Similarity	NPC262156
0.9174	High Similarity	NPC113865
0.9174	High Similarity	NPC343720
0.9167	High Similarity	NPC232316
0.9167	High Similarity	NPC165133
0.9167	High Similarity	NPC117780
0.9167	High Similarity	NPC242885
0.9167	High Similarity	NPC229401
0.9167	High Similarity	NPC56214
0.9167	High Similarity	NPC227217
0.9167	High Similarity	NPC95614
0.9153	High Similarity	NPC141090
0.9153	High Similarity	NPC193067
0.9153	High Similarity	NPC123948
0.9147	High Similarity	NPC202846
0.9147	High Similarity	NPC16435
0.9147	High Similarity	NPC248727
0.9147	High Similarity	NPC265433
0.9147	High Similarity	NPC143139
0.9147	High Similarity	NPC227503

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 NPC251855 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	349
0.1-0.2	960
0.2-0.3	1756
0.3-0.4	2767
0.4-0.5	1638
0.5-0.6	918
0.6-0.7	613
0.7-0.8	131
0.8-0.85	12
0.85-0.9	5
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.9672	High Similarity	NPD3027	Phase 3
0.8968	High Similarity	NPD1529	Clinical (unspecified phase)
0.8889	High Similarity	NPD1530	Clinical (unspecified phase)
0.8837	High Similarity	NPD1613	Approved
0.8837	High Similarity	NPD1612	Clinical (unspecified phase)
0.8729	High Similarity	NPD228	Approved
0.872	High Similarity	NPD2982	Phase 2
0.872	High Similarity	NPD2983	Phase 2
0.864	High Similarity	NPD2981	Phase 2
0.8594	High Similarity	NPD3018	Phase 2
0.8583	High Similarity	NPD5283	Phase 1
0.8425	Intermediate Similarity	NPD4379	Clinical (unspecified phase)
0.825	Intermediate Similarity	NPD3021	Approved
0.825	Intermediate Similarity	NPD3022	Approved
0.8244	Intermediate Similarity	NPD4908	Phase 1
0.8125	Intermediate Similarity	NPD1610	Phase 2
0.812	Intermediate Similarity	NPD4907	Clinical (unspecified phase)
0.8095	Intermediate Similarity	NPD1548	Phase 1
0.8014	Intermediate Similarity	NPD1934	Approved
0.8	Intermediate Similarity	NPD1558	Phase 1
0.7959	Intermediate Similarity	NPD2801	Approved
0.7914	Intermediate Similarity	NPD3540	Phase 1
0.791	Intermediate Similarity	NPD4625	Phase 3
0.7881	Intermediate Similarity	NPD1242	Phase 1
0.7874	Intermediate Similarity	NPD5536	Phase 2
0.7868	Intermediate Similarity	NPD3620	Phase 2
0.7868	Intermediate Similarity	NPD3619	Clinical (unspecified phase)
0.7863	Intermediate Similarity	NPD4749	Approved
0.7852	Intermediate Similarity	NPD3882	Suspended
0.7842	Intermediate Similarity	NPD3539	Phase 1
0.7838	Intermediate Similarity	NPD2393	Clinical (unspecified phase)
0.7832	Intermediate Similarity	NPD4357	Discontinued
0.7817	Intermediate Similarity	NPD5307	Clinical (unspecified phase)
0.7762	Intermediate Similarity	NPD7124	Phase 2
0.7748	Intermediate Similarity	NPD6234	Discontinued
0.7727	Intermediate Similarity	NPD3600	Clinical (unspecified phase)
0.7724	Intermediate Similarity	NPD2684	Approved
0.771	Intermediate Similarity	NPD3705	Approved
0.7708	Intermediate Similarity	NPD1511	Approved
0.7687	Intermediate Similarity	NPD6917	Clinical (unspecified phase)
0.7687	Intermediate Similarity	NPD4005	Discontinued
0.7676	Intermediate Similarity	NPD3060	Approved
0.7667	Intermediate Similarity	NPD846	Approved
0.7667	Intermediate Similarity	NPD940	Approved
0.7664	Intermediate Similarity	NPD2674	Phase 3
0.7651	Intermediate Similarity	NPD37	Approved
0.7635	Intermediate Similarity	NPD4675	Approved
0.7635	Intermediate Similarity	NPD4678	Approved
0.763	Intermediate Similarity	NPD2861	Phase 2
0.7619	Intermediate Similarity	NPD1653	Approved
0.7619	Intermediate Similarity	NPD7843	Approved
0.7616	Intermediate Similarity	NPD4868	Clinical (unspecified phase)
0.7615	Intermediate Similarity	NPD1357	Approved
0.7613	Intermediate Similarity	NPD6166	Phase 2
0.7613	Intermediate Similarity	NPD6167	Clinical (unspecified phase)
0.7613	Intermediate Similarity	NPD6168	Clinical (unspecified phase)
0.7609	Intermediate Similarity	NPD4060	Phase 1
0.7603	Intermediate Similarity	NPD1512	Approved
0.7591	Intermediate Similarity	NPD6859	Clinical (unspecified phase)
0.7591	Intermediate Similarity	NPD6410	Clinical (unspecified phase)
0.7586	Intermediate Similarity	NPD6143	Clinical (unspecified phase)
0.7578	Intermediate Similarity	NPD7157	Approved
0.7576	Intermediate Similarity	NPD422	Phase 1
0.7571	Intermediate Similarity	NPD6111	Discontinued
0.7569	Intermediate Similarity	NPD2219	Phase 1
0.7551	Intermediate Similarity	NPD6980	Clinical (unspecified phase)
0.7542	Intermediate Similarity	NPD2860	Approved
0.7542	Intermediate Similarity	NPD2859	Approved
0.7535	Intermediate Similarity	NPD7266	Discontinued
0.752	Intermediate Similarity	NPD4750	Phase 3
0.75	Intermediate Similarity	NPD3020	Approved
0.75	Intermediate Similarity	NPD4967	Phase 2
0.75	Intermediate Similarity	NPD4966	Approved
0.75	Intermediate Similarity	NPD4965	Approved
0.7484	Intermediate Similarity	NPD6232	Discontinued
0.7482	Intermediate Similarity	NPD1240	Approved
0.7464	Intermediate Similarity	NPD5109	Approved
0.7464	Intermediate Similarity	NPD5110	Phase 2
0.7464	Intermediate Similarity	NPD3144	Approved
0.7464	Intermediate Similarity	NPD5111	Phase 2
0.7464	Intermediate Similarity	NPD3145	Approved
0.7458	Intermediate Similarity	NPD2934	Approved
0.7458	Intermediate Similarity	NPD2933	Approved
0.7458	Intermediate Similarity	NPD9296	Approved
0.7451	Intermediate Similarity	NPD7975	Clinical (unspecified phase)
0.7442	Intermediate Similarity	NPD6671	Approved
0.7434	Intermediate Similarity	NPD3817	Phase 2
0.7431	Intermediate Similarity	NPD4236	Phase 3
0.7431	Intermediate Similarity	NPD4237	Approved
0.7429	Intermediate Similarity	NPD230	Phase 1
0.7426	Intermediate Similarity	NPD6584	Phase 3
0.7421	Intermediate Similarity	NPD7074	Phase 3
0.7419	Intermediate Similarity	NPD7199	Phase 2
0.7405	Intermediate Similarity	NPD3818	Discontinued
0.7405	Intermediate Similarity	NPD7228	Approved
0.7394	Intermediate Similarity	NPD1510	Phase 2
0.7391	Intermediate Similarity	NPD7095	Approved
0.7381	Intermediate Similarity	NPD5451	Approved
0.7376	Intermediate Similarity	NPD1607	Approved
0.7372	Intermediate Similarity	NPD9494	Approved
0.7358	Intermediate Similarity	NPD7054	Approved
0.7357	Intermediate Similarity	NPD943	Approved
0.7342	Intermediate Similarity	NPD7473	Discontinued
0.7338	Intermediate Similarity	NPD4055	Discovery
0.7333	Intermediate Similarity	NPD6055	Clinical (unspecified phase)
0.7325	Intermediate Similarity	NPD7184	Clinical (unspecified phase)
0.7324	Intermediate Similarity	NPD4537	Clinical (unspecified phase)
0.7324	Intermediate Similarity	NPD4536	Approved
0.7324	Intermediate Similarity	NPD4538	Approved
0.732	Intermediate Similarity	NPD6374	Clinical (unspecified phase)
0.7319	Intermediate Similarity	NPD5752	Clinical (unspecified phase)
0.7313	Intermediate Similarity	NPD1091	Approved
0.7312	Intermediate Similarity	NPD7472	Approved
0.731	Intermediate Similarity	NPD5698	Clinical (unspecified phase)
0.731	Intermediate Similarity	NPD5177	Phase 3
0.7297	Intermediate Similarity	NPD4378	Clinical (unspecified phase)
0.7297	Intermediate Similarity	NPD4123	Phase 3
0.7297	Intermediate Similarity	NPD7447	Phase 1
0.7293	Intermediate Similarity	NPD6516	Phase 2
0.7293	Intermediate Similarity	NPD5846	Approved
0.7292	Intermediate Similarity	NPD2029	Clinical (unspecified phase)
0.7285	Intermediate Similarity	NPD4380	Phase 2
0.728	Intermediate Similarity	NPD968	Approved
0.7279	Intermediate Similarity	NPD8651	Approved
0.7279	Intermediate Similarity	NPD2922	Phase 1
0.7255	Intermediate Similarity	NPD1465	Phase 2
0.7255	Intermediate Similarity	NPD2978	Approved
0.7255	Intermediate Similarity	NPD2977	Approved
0.7248	Intermediate Similarity	NPD1940	Clinical (unspecified phase)
0.7248	Intermediate Similarity	NPD5261	Clinical (unspecified phase)
0.7239	Intermediate Similarity	NPD3847	Discontinued
0.7234	Intermediate Similarity	NPD2238	Phase 2
0.723	Intermediate Similarity	NPD7213	Phase 3
0.723	Intermediate Similarity	NPD7212	Phase 2
0.7222	Intermediate Similarity	NPD2935	Discontinued
0.7222	Intermediate Similarity	NPD6100	Approved
0.7222	Intermediate Similarity	NPD6099	Approved
0.7222	Intermediate Similarity	NPD290	Approved
0.7219	Intermediate Similarity	NPD7261	Clinical (unspecified phase)
0.7214	Intermediate Similarity	NPD5718	Phase 2
0.7211	Intermediate Similarity	NPD6190	Approved
0.7209	Intermediate Similarity	NPD5535	Approved
0.7206	Intermediate Similarity	NPD6582	Phase 2
0.7206	Intermediate Similarity	NPD6583	Phase 3
0.7203	Intermediate Similarity	NPD6895	Approved
0.7203	Intermediate Similarity	NPD6896	Approved
0.7195	Intermediate Similarity	NPD8053	Approved
0.7195	Intermediate Similarity	NPD8054	Approved
0.7192	Intermediate Similarity	NPD4162	Approved
0.7192	Intermediate Similarity	NPD6674	Discontinued
0.7172	Intermediate Similarity	NPD1550	Clinical (unspecified phase)
0.7172	Intermediate Similarity	NPD1375	Discontinued
0.7172	Intermediate Similarity	NPD1552	Clinical (unspecified phase)
0.7164	Intermediate Similarity	NPD4626	Approved
0.7164	Intermediate Similarity	NPD2668	Approved
0.7164	Intermediate Similarity	NPD2667	Approved
0.716	Intermediate Similarity	NPD6797	Phase 2
0.7153	Intermediate Similarity	NPD5960	Phase 3
0.7153	Intermediate Similarity	NPD5588	Approved
0.7143	Intermediate Similarity	NPD4110	Phase 3
0.7143	Intermediate Similarity	NPD3892	Phase 2
0.7143	Intermediate Similarity	NPD3750	Approved
0.7143	Intermediate Similarity	NPD5844	Phase 1
0.7143	Intermediate Similarity	NPD6331	Phase 2
0.7143	Intermediate Similarity	NPD4628	Phase 3
0.7143	Intermediate Similarity	NPD4109	Clinical (unspecified phase)
0.7132	Intermediate Similarity	NPD2230	Approved
0.7132	Intermediate Similarity	NPD1608	Approved
0.7132	Intermediate Similarity	NPD2232	Approved
0.7132	Intermediate Similarity	NPD2233	Approved
0.7124	Intermediate Similarity	NPD5090	Approved
0.7124	Intermediate Similarity	NPD5089	Approved
0.7123	Intermediate Similarity	NPD1549	Phase 2
0.7123	Intermediate Similarity	NPD970	Clinical (unspecified phase)
0.7117	Intermediate Similarity	NPD7251	Discontinued
0.7115	Intermediate Similarity	NPD7075	Discontinued
0.7114	Intermediate Similarity	NPD6799	Approved
0.7114	Intermediate Similarity	NPD5297	Approved
0.7097	Intermediate Similarity	NPD291	Approved
0.7095	Intermediate Similarity	NPD5241	Discontinued
0.7092	Intermediate Similarity	NPD6798	Discontinued
0.7091	Intermediate Similarity	NPD7090	Clinical (unspecified phase)
0.709	Intermediate Similarity	NPD1651	Approved
0.708	Intermediate Similarity	NPD1669	Approved
0.7075	Intermediate Similarity	NPD1652	Phase 2
0.7073	Intermediate Similarity	NPD4338	Clinical (unspecified phase)
0.7073	Intermediate Similarity	NPD7808	Phase 3
0.7063	Intermediate Similarity	NPD4340	Discontinued
0.7063	Intermediate Similarity	NPD6355	Discontinued
0.7063	Intermediate Similarity	NPD3657	Discovery
0.7063	Intermediate Similarity	NPD5123	Clinical (unspecified phase)
0.7063	Intermediate Similarity	NPD5735	Approved
0.7063	Intermediate Similarity	NPD5124	Phase 1
0.7055	Intermediate Similarity	NPD7993	Clinical (unspecified phase)
0.7054	Intermediate Similarity	NPD9280	Clinical (unspecified phase)
0.7051	Intermediate Similarity	NPD6788	Approved
0.705	Intermediate Similarity	NPD4624	Approved
0.7047	Intermediate Similarity	NPD5058	Phase 3
0.7042	Intermediate Similarity	NPD6233	Phase 2
0.7042	Intermediate Similarity	NPD1726	Clinical (unspecified phase)

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