NPASS Compound

Structure

NPC470096 OpenBabel07101719512D 31 32 0 0 1 0 0 0 0 0999 V2000 4.3301 0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 7.7942 3.5000 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 -3.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4641 -0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.9282 -0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 7.7942 0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1962 -0.0000 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 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 6.0622 -1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0622 0.5000 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 5.1962 -1.0000 0.0000 C 0 0 3 0 0 0 0 0 0 0 0 0 7.7942 1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4641 -1.0000 0.0000 C 0 0 3 0 0 0 0 0 0 0 0 0 6.9282 2.0000 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 2.5981 -1.5000 0.0000 C 0 0 3 0 0 0 0 0 0 0 0 0 6.9282 -1.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 8.6603 2.0000 0.0000 O 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 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 2.5981 -2.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 4.3301 -1.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 6 1 0 0 0 0 2 27 1 0 0 0 0 3 28 1 0 0 0 0 4 29 1 0 0 0 0 5 30 1 0 0 0 0 6 18 1 0 0 0 0 7 8 2 0 0 0 0 7 14 1 0 0 0 0 8 17 1 0 0 0 0 9 14 1 0 0 0 0 9 16 1 0 0 0 0 10 14 2 0 0 0 0 10 19 1 0 0 0 0 11 15 2 0 0 0 0 11 20 1 0 0 0 0 12 15 1 0 0 0 0 12 21 2 0 0 0 0 13 16 1 0 0 0 0 13 24 1 0 0 0 0 15 23 1 0 0 0 0 16 31 1 0 0 0 0 17 19 2 0 0 0 0 17 25 1 0 0 0 0 18 23 1 0 0 0 0 18 31 1 0 0 0 0 19 27 1 0 0 0 0 20 22 2 0 0 0 0 20 28 1 0 0 0 0 21 22 1 0 0 0 0 21 29 1 0 0 0 0 22 26 1 0 0 0 0 23 30 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	436.21
Volume:	443.754
LogP:	2.233
LogD:	2.84
LogS:	-3.822
# Rotatable Bonds:	12
TPSA:	106.84
# H-Bond Aceptor:	8
# H-Bond Donor:	3
# Rings:	2
# Heavy Atoms:	8

MedChem Properties

QED Drug-Likeness Score:	0.466
Synthetic Accessibility Score:	3.709
Fsp3:	0.478
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Accepted
GSK Rule:	Rejected
BMS Rule:	0
Golden Triangle Rule:	Accepted
Chelating Alert:	1
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-4.691
MDCK Permeability:	1.7835745893535204e-05
Pgp-inhibitor:	0.16
Pgp-substrate:	0.225
Human Intestinal Absorption (HIA):	0.014
20% Bioavailability (F20%):	0.043
30% Bioavailability (F30%):	0.11

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.068
Plasma Protein Binding (PPB):	93.51065063476562%
Volume Distribution (VD):	0.528
Pgp-substrate:	6.580844402313232%

ADMET: Metabolism

CYP1A2-inhibitor:	0.022
CYP1A2-substrate:	0.764
CYP2C19-inhibitor:	0.031
CYP2C19-substrate:	0.881
CYP2C9-inhibitor:	0.064
CYP2C9-substrate:	0.574
CYP2D6-inhibitor:	0.075
CYP2D6-substrate:	0.878
CYP3A4-inhibitor:	0.527
CYP3A4-substrate:	0.907

ADMET: Excretion

Clearance (CL):	13.271
Half-life (T1/2):	0.826

ADMET: Toxicity

hERG Blockers:	0.051
Human Hepatotoxicity (H-HT):	0.232
Drug-inuced Liver Injury (DILI):	0.035
AMES Toxicity:	0.167
Rat Oral Acute Toxicity:	0.045
Maximum Recommended Daily Dose:	0.272
Skin Sensitization:	0.834
Carcinogencity:	0.046
Eye Corrosion:	0.003
Eye Irritation:	0.024
Respiratory Toxicity:	0.14

Download Data

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

Natural Product: NPC470096

Natural Product ID:	NPC470096
*Common Name:**	(-)-Threo-4,9,4',9'-Tetrahydroxy-3,5,7,3'-Tetramethoxy-8-O-8'-Neolignan
IUPAC Name:	4-[2-[1-hydroxy-3-(4-hydroxy-3-methoxyphenyl)propan-2-yl]oxy-1-methoxybutyl]-2,6-dimethoxyphenol
Synonyms:
Standard InCHIKey:	IXDWWAKFBJRMEW-UHFFFAOYSA-N
Standard InCHI:	InChI=1S/C23H32O8/c1-6-18(23(30-5)15-11-20(28-3)22(26)21(12-15)29-4)31-16(13-24)9-14-7-8-17(25)19(10-14)27-2/h7-8,10-12,16,18,23-26H,6,9,13H2,1-5H3
SMILES:	OCC(OC(C(c1cc(OC)c(c(c1)OC)O)OC)CC)Cc1ccc(c(c1)OC)O
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL1761709
PubChem CID:	54582333
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
NPO29118	Euonymus alatus	Species	Celastraceae	Eukaryota	leaves and twigs	n.a.	n.a.	PMID[21435874]
NPO29118	Euonymus alatus	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO29118	Euonymus alatus	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO29118	Euonymus alatus	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO29118	Euonymus alatus	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO29118	Euonymus alatus	Species	Celastraceae	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
Cell Line	1

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT113	Cell Line	RAW264.7	Mus musculus	IC50	=	41900.0	nM	PMID[554297]

☑ 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 NPC470096 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	380
0.1-0.2	1463
0.2-0.3	4709
0.3-0.4	12181
0.4-0.5	5873
0.5-0.6	4379
0.6-0.7	7100
0.7-0.8	4722
0.8-0.85	1051
0.85-0.9	545
0.9-0.95	254
0.95-1	40

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC470095
0.9762	High Similarity	NPC184447
0.9762	High Similarity	NPC7903
0.9762	High Similarity	NPC35932
0.9762	High Similarity	NPC160991
0.9762	High Similarity	NPC16208
0.9683	High Similarity	NPC472597
0.9683	High Similarity	NPC469613
0.9683	High Similarity	NPC30043
0.9683	High Similarity	NPC469625
0.968	High Similarity	NPC170844
0.968	High Similarity	NPC476968
0.9609	High Similarity	NPC170694
0.9609	High Similarity	NPC310854
0.9606	High Similarity	NPC253105
0.9606	High Similarity	NPC201587
0.9606	High Similarity	NPC470752
0.9603	High Similarity	NPC469614
0.9603	High Similarity	NPC469612
0.9603	High Similarity	NPC472338
0.96	High Similarity	NPC206615
0.96	High Similarity	NPC470213
0.96	High Similarity	NPC98631
0.96	High Similarity	NPC186843
0.9528	High Similarity	NPC309787
0.9528	High Similarity	NPC474017
0.9524	High Similarity	NPC226788
0.9524	High Similarity	NPC285339
0.9524	High Similarity	NPC218856
0.9524	High Similarity	NPC202582
0.9524	High Similarity	NPC222004
0.9524	High Similarity	NPC3439
0.9524	High Similarity	NPC273295
0.9524	High Similarity	NPC210623
0.9524	High Similarity	NPC190629
0.9524	High Similarity	NPC470258
0.9457	High Similarity	NPC244983
0.9457	High Similarity	NPC326095
0.9457	High Similarity	NPC287745
0.9394	High Similarity	NPC266197
0.9394	High Similarity	NPC291101
0.9385	High Similarity	NPC472337
0.938	High Similarity	NPC475840
0.938	High Similarity	NPC158331
0.937	High Similarity	NPC212015
0.9365	High Similarity	NPC147821
0.9365	High Similarity	NPC118787
0.9365	High Similarity	NPC183181
0.9365	High Similarity	NPC210355
0.9365	High Similarity	NPC163332
0.9365	High Similarity	NPC111247
0.9365	High Similarity	NPC474119
0.9365	High Similarity	NPC41706
0.9365	High Similarity	NPC319625
0.9365	High Similarity	NPC292056
0.936	High Similarity	NPC203133
0.936	High Similarity	NPC233410
0.936	High Similarity	NPC208950
0.936	High Similarity	NPC298757
0.936	High Similarity	NPC193544
0.936	High Similarity	NPC472093
0.936	High Similarity	NPC116907
0.936	High Similarity	NPC251855
0.936	High Similarity	NPC17943
0.936	High Similarity	NPC221077
0.936	High Similarity	NPC117214
0.936	High Similarity	NPC475169
0.936	High Similarity	NPC57490
0.9355	High Similarity	NPC220598
0.9355	High Similarity	NPC165375
0.9318	High Similarity	NPC22517
0.9313	High Similarity	NPC306441
0.9313	High Similarity	NPC471719
0.9313	High Similarity	NPC16435
0.9313	High Similarity	NPC472336
0.9313	High Similarity	NPC472334
0.9302	High Similarity	NPC204215
0.9302	High Similarity	NPC175067
0.9291	High Similarity	NPC252307
0.9291	High Similarity	NPC245826
0.9291	High Similarity	NPC474178
0.9286	High Similarity	NPC18924
0.9286	High Similarity	NPC58607
0.9286	High Similarity	NPC78974
0.9286	High Similarity	NPC214406
0.9286	High Similarity	NPC223136
0.9286	High Similarity	NPC178284
0.9286	High Similarity	NPC28730
0.9286	High Similarity	NPC103823
0.9286	High Similarity	NPC191037
0.9286	High Similarity	NPC44748
0.9274	High Similarity	NPC71579
0.9274	High Similarity	NPC262253
0.9274	High Similarity	NPC473411
0.9254	High Similarity	NPC469559
0.9248	High Similarity	NPC267291
0.9237	High Similarity	NPC234333
0.9237	High Similarity	NPC165155
0.9237	High Similarity	NPC99572
0.9237	High Similarity	NPC94750
0.9237	High Similarity	NPC24490
0.9237	High Similarity	NPC47398
0.9237	High Similarity	NPC121812
0.9237	High Similarity	NPC61946
0.9237	High Similarity	NPC34103
0.9237	High Similarity	NPC470356
0.9237	High Similarity	NPC126409
0.9237	High Similarity	NPC112246
0.9237	High Similarity	NPC256262
0.9237	High Similarity	NPC474206
0.9237	High Similarity	NPC141765
0.9237	High Similarity	NPC112939
0.9237	High Similarity	NPC260898
0.9231	High Similarity	NPC168059
0.9231	High Similarity	NPC229442
0.9219	High Similarity	NPC86030
0.9219	High Similarity	NPC58164
0.9219	High Similarity	NPC10225
0.9219	High Similarity	NPC5851
0.9213	High Similarity	NPC124452
0.9213	High Similarity	NPC118533
0.9213	High Similarity	NPC282000
0.9213	High Similarity	NPC159968
0.9213	High Similarity	NPC165045
0.9213	High Similarity	NPC242032
0.9213	High Similarity	NPC293054
0.9213	High Similarity	NPC236791
0.9213	High Similarity	NPC470699
0.9213	High Similarity	NPC324112
0.9213	High Similarity	NPC127587
0.9213	High Similarity	NPC169474
0.9213	High Similarity	NPC246620
0.9213	High Similarity	NPC74817
0.9213	High Similarity	NPC82679
0.9206	High Similarity	NPC60885
0.9206	High Similarity	NPC234400
0.9206	High Similarity	NPC194519
0.9206	High Similarity	NPC299584
0.9206	High Similarity	NPC265483
0.9206	High Similarity	NPC82483
0.92	High Similarity	NPC471693
0.92	High Similarity	NPC282496
0.92	High Similarity	NPC197757
0.92	High Similarity	NPC136319
0.92	High Similarity	NPC228922
0.92	High Similarity	NPC233526
0.9194	High Similarity	NPC470804
0.9194	High Similarity	NPC49341
0.9167	High Similarity	NPC474639
0.9167	High Similarity	NPC227503
0.9167	High Similarity	NPC230734
0.9167	High Similarity	NPC302701
0.9167	High Similarity	NPC269091
0.916	High Similarity	NPC309744
0.916	High Similarity	NPC107478
0.9147	High Similarity	NPC187998
0.9147	High Similarity	NPC77040
0.9147	High Similarity	NPC153739
0.9147	High Similarity	NPC42300
0.9147	High Similarity	NPC311680
0.9147	High Similarity	NPC51840
0.9147	High Similarity	NPC64201
0.9147	High Similarity	NPC299221
0.9147	High Similarity	NPC92164
0.9147	High Similarity	NPC174495
0.9147	High Similarity	NPC257582
0.9147	High Similarity	NPC145305
0.9147	High Similarity	NPC242807
0.9147	High Similarity	NPC234488
0.9147	High Similarity	NPC241522
0.9141	High Similarity	NPC72529
0.9134	High Similarity	NPC76451
0.9134	High Similarity	NPC181361
0.9127	High Similarity	NPC228972
0.9127	High Similarity	NPC94276
0.9127	High Similarity	NPC293701
0.9127	High Similarity	NPC122792
0.9127	High Similarity	NPC48990
0.9127	High Similarity	NPC114901
0.9127	High Similarity	NPC109822
0.912	High Similarity	NPC41562
0.9118	High Similarity	NPC470097
0.9118	High Similarity	NPC114119
0.9118	High Similarity	NPC471415
0.9113	High Similarity	NPC166759
0.9111	High Similarity	NPC472714
0.9111	High Similarity	NPC193722
0.9111	High Similarity	NPC5262
0.9111	High Similarity	NPC189115
0.9111	High Similarity	NPC278469
0.9098	High Similarity	NPC107551
0.9098	High Similarity	NPC326797
0.9098	High Similarity	NPC474282
0.9098	High Similarity	NPC211549
0.9098	High Similarity	NPC102904
0.9098	High Similarity	NPC176051
0.9098	High Similarity	NPC474390
0.9098	High Similarity	NPC103976
0.9091	High Similarity	NPC164787
0.9091	High Similarity	NPC151224

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 NPC470096 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	323
0.1-0.2	854
0.2-0.3	1933
0.3-0.4	2746
0.4-0.5	1590
0.5-0.6	932
0.6-0.7	618
0.7-0.8	141
0.8-0.85	10
0.85-0.9	0
0.9-0.95	2
0.95-1	1

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.968	High Similarity	NPD3027	Phase 3
0.9008	High Similarity	NPD1612	Clinical (unspecified phase)
0.9008	High Similarity	NPD1613	Approved
0.8702	High Similarity	NPD1529	Clinical (unspecified phase)
0.8626	High Similarity	NPD1530	Clinical (unspecified phase)
0.8462	Intermediate Similarity	NPD2983	Phase 2
0.8462	Intermediate Similarity	NPD2982	Phase 2
0.8385	Intermediate Similarity	NPD2981	Phase 2
0.8346	Intermediate Similarity	NPD3018	Phase 2
0.8306	Intermediate Similarity	NPD228	Approved
0.8085	Intermediate Similarity	NPD7266	Discontinued
0.8054	Intermediate Similarity	NPD1934	Approved
0.8045	Intermediate Similarity	NPD4379	Clinical (unspecified phase)
0.8031	Intermediate Similarity	NPD5283	Phase 1
0.8027	Intermediate Similarity	NPD1653	Approved
0.8015	Intermediate Similarity	NPD4908	Phase 1
0.8	Intermediate Similarity	NPD1548	Phase 1
0.7908	Intermediate Similarity	NPD6234	Discontinued
0.7899	Intermediate Similarity	NPD4907	Clinical (unspecified phase)
0.7895	Intermediate Similarity	NPD1610	Phase 2
0.7885	Intermediate Similarity	NPD6168	Clinical (unspecified phase)
0.7885	Intermediate Similarity	NPD6167	Clinical (unspecified phase)
0.7885	Intermediate Similarity	NPD6166	Phase 2
0.7881	Intermediate Similarity	NPD2801	Approved
0.7881	Intermediate Similarity	NPD2393	Clinical (unspecified phase)
0.7848	Intermediate Similarity	NPD7054	Approved
0.7815	Intermediate Similarity	NPD37	Approved
0.7812	Intermediate Similarity	NPD7843	Approved
0.7799	Intermediate Similarity	NPD7074	Phase 3
0.7799	Intermediate Similarity	NPD7472	Approved
0.7786	Intermediate Similarity	NPD3620	Phase 2
0.7786	Intermediate Similarity	NPD3619	Clinical (unspecified phase)
0.7786	Intermediate Similarity	NPD1558	Phase 1
0.7785	Intermediate Similarity	NPD7228	Approved
0.7778	Intermediate Similarity	NPD3882	Suspended
0.7778	Intermediate Similarity	NPD4966	Approved
0.7778	Intermediate Similarity	NPD4967	Phase 2
0.7778	Intermediate Similarity	NPD4868	Clinical (unspecified phase)
0.7778	Intermediate Similarity	NPD4965	Approved
0.7769	Intermediate Similarity	NPD7157	Approved
0.7761	Intermediate Similarity	NPD3705	Approved
0.774	Intermediate Similarity	NPD5307	Clinical (unspecified phase)
0.7727	Intermediate Similarity	NPD7975	Clinical (unspecified phase)
0.7724	Intermediate Similarity	NPD3060	Approved
0.7717	Intermediate Similarity	NPD3021	Approved
0.7717	Intermediate Similarity	NPD3022	Approved
0.7712	Intermediate Similarity	NPD6374	Clinical (unspecified phase)
0.7708	Intermediate Similarity	NPD3540	Phase 1
0.7682	Intermediate Similarity	NPD4678	Approved
0.7682	Intermediate Similarity	NPD4675	Approved
0.7681	Intermediate Similarity	NPD2861	Phase 2
0.7673	Intermediate Similarity	NPD3818	Discontinued
0.7669	Intermediate Similarity	NPD1357	Approved
0.7643	Intermediate Similarity	NPD6859	Clinical (unspecified phase)
0.7643	Intermediate Similarity	NPD6410	Clinical (unspecified phase)
0.7639	Intermediate Similarity	NPD3539	Phase 1
0.7638	Intermediate Similarity	NPD2684	Approved
0.7635	Intermediate Similarity	NPD1511	Approved
0.763	Intermediate Similarity	NPD1091	Approved
0.7619	Intermediate Similarity	NPD6190	Approved
0.7616	Intermediate Similarity	NPD6055	Clinical (unspecified phase)
0.7609	Intermediate Similarity	NPD6917	Clinical (unspecified phase)
0.7603	Intermediate Similarity	NPD4236	Phase 3
0.7603	Intermediate Similarity	NPD4237	Approved
0.7597	Intermediate Similarity	NPD3817	Phase 2
0.7593	Intermediate Similarity	NPD7251	Discontinued
0.7571	Intermediate Similarity	NPD4625	Phase 3
0.7566	Intermediate Similarity	NPD4380	Phase 2
0.7546	Intermediate Similarity	NPD7808	Phase 3
0.7533	Intermediate Similarity	NPD1512	Approved
0.7531	Intermediate Similarity	NPD6797	Phase 2
0.7519	Intermediate Similarity	NPD5536	Phase 2
0.7518	Intermediate Similarity	NPD4749	Approved
0.7517	Intermediate Similarity	NPD4357	Discontinued
0.75	Intermediate Similarity	NPD4536	Approved
0.75	Intermediate Similarity	NPD4538	Approved
0.75	Intermediate Similarity	NPD4537	Clinical (unspecified phase)
0.75	Intermediate Similarity	NPD1242	Phase 1
0.75	Intermediate Similarity	NPD4005	Discontinued
0.7483	Intermediate Similarity	NPD230	Phase 1
0.7483	Intermediate Similarity	NPD6674	Discontinued
0.7483	Intermediate Similarity	NPD5698	Clinical (unspecified phase)
0.7468	Intermediate Similarity	NPD7199	Phase 2
0.745	Intermediate Similarity	NPD7124	Phase 2
0.7439	Intermediate Similarity	NPD4338	Clinical (unspecified phase)
0.7422	Intermediate Similarity	NPD290	Approved
0.7419	Intermediate Similarity	NPD2978	Approved
0.7419	Intermediate Similarity	NPD2977	Approved
0.7413	Intermediate Similarity	NPD4060	Phase 1
0.7383	Intermediate Similarity	NPD2219	Phase 1
0.7376	Intermediate Similarity	NPD5752	Clinical (unspecified phase)
0.7372	Intermediate Similarity	NPD422	Phase 1
0.7368	Intermediate Similarity	NPD6671	Approved
0.7365	Intermediate Similarity	NPD1652	Phase 2
0.7365	Intermediate Similarity	NPD5177	Phase 3
0.7365	Intermediate Similarity	NPD4162	Approved
0.7351	Intermediate Similarity	NPD4123	Phase 3
0.7347	Intermediate Similarity	NPD2029	Clinical (unspecified phase)
0.7344	Intermediate Similarity	NPD968	Approved
0.7343	Intermediate Similarity	NPD2674	Phase 3
0.7338	Intermediate Similarity	NPD8651	Approved
0.7329	Intermediate Similarity	NPD5960	Phase 3
0.7329	Intermediate Similarity	NPD5588	Approved
0.7317	Intermediate Similarity	NPD7993	Clinical (unspecified phase)
0.7312	Intermediate Similarity	NPD6232	Discontinued
0.7302	Intermediate Similarity	NPD291	Approved
0.7301	Intermediate Similarity	NPD5844	Phase 1
0.7292	Intermediate Similarity	NPD2238	Phase 2
0.7285	Intermediate Similarity	NPD6143	Clinical (unspecified phase)
0.7284	Intermediate Similarity	NPD7473	Discontinued
0.7278	Intermediate Similarity	NPD7075	Discontinued
0.7278	Intermediate Similarity	NPD4381	Clinical (unspecified phase)
0.7273	Intermediate Similarity	NPD7240	Approved
0.7267	Intermediate Similarity	NPD7184	Clinical (unspecified phase)
0.7267	Intermediate Similarity	NPD2677	Approved
0.7266	Intermediate Similarity	NPD3600	Clinical (unspecified phase)
0.726	Intermediate Similarity	NPD6111	Discontinued
0.7255	Intermediate Similarity	NPD6980	Clinical (unspecified phase)
0.7241	Intermediate Similarity	NPD5735	Approved
0.7237	Intermediate Similarity	NPD7447	Phase 1
0.7234	Intermediate Similarity	NPD6584	Phase 3
0.7226	Intermediate Similarity	NPD5846	Approved
0.7226	Intermediate Similarity	NPD6516	Phase 2
0.7222	Intermediate Similarity	NPD6233	Phase 2
0.7219	Intermediate Similarity	NPD5058	Phase 3
0.7208	Intermediate Similarity	NPD3687	Approved
0.7208	Intermediate Similarity	NPD3686	Approved
0.7203	Intermediate Similarity	NPD7095	Approved
0.72	Intermediate Similarity	NPD4628	Phase 3
0.7197	Intermediate Similarity	NPD5772	Approved
0.7197	Intermediate Similarity	NPD1465	Phase 2
0.7197	Intermediate Similarity	NPD5773	Approved
0.7197	Intermediate Similarity	NPD6818	Clinical (unspecified phase)
0.7194	Intermediate Similarity	NPD2235	Phase 2
0.7194	Intermediate Similarity	NPD2231	Phase 2
0.7192	Intermediate Similarity	NPD5314	Approved
0.7192	Intermediate Similarity	NPD6653	Approved
0.719	Intermediate Similarity	NPD1940	Clinical (unspecified phase)
0.7183	Intermediate Similarity	NPD9494	Approved
0.7172	Intermediate Similarity	NPD3059	Approved
0.7172	Intermediate Similarity	NPD3061	Approved
0.7172	Intermediate Similarity	NPD3062	Approved
0.7171	Intermediate Similarity	NPD7212	Phase 2
0.7171	Intermediate Similarity	NPD7213	Phase 3
0.7169	Intermediate Similarity	NPD7685	Pre-registration
0.7165	Intermediate Similarity	NPD940	Approved
0.7165	Intermediate Similarity	NPD846	Approved
0.7153	Intermediate Similarity	NPD3145	Approved
0.7153	Intermediate Similarity	NPD3144	Approved
0.7152	Intermediate Similarity	NPD5241	Discontinued
0.7152	Intermediate Similarity	NPD5402	Approved
0.7124	Intermediate Similarity	NPD4378	Clinical (unspecified phase)
0.7123	Intermediate Similarity	NPD5123	Clinical (unspecified phase)
0.7123	Intermediate Similarity	NPD5124	Phase 1
0.7123	Intermediate Similarity	NPD6355	Discontinued
0.7114	Intermediate Similarity	NPD5762	Approved
0.7114	Intermediate Similarity	NPD5763	Approved
0.7114	Intermediate Similarity	NPD1375	Discontinued
0.7114	Intermediate Similarity	NPD1552	Clinical (unspecified phase)
0.7114	Intermediate Similarity	NPD1550	Clinical (unspecified phase)
0.7103	Intermediate Similarity	NPD1726	Clinical (unspecified phase)
0.7101	Intermediate Similarity	NPD8055	Clinical (unspecified phase)
0.7101	Intermediate Similarity	NPD9384	Approved
0.7101	Intermediate Similarity	NPD9381	Approved
0.7097	Intermediate Similarity	NPD9296	Approved
0.7097	Intermediate Similarity	NPD2934	Approved
0.7097	Intermediate Similarity	NPD2933	Approved
0.7095	Intermediate Similarity	NPD1510	Phase 2
0.7091	Intermediate Similarity	NPD7804	Clinical (unspecified phase)
0.7089	Intermediate Similarity	NPD7096	Clinical (unspecified phase)
0.7086	Intermediate Similarity	NPD6331	Phase 2
0.7086	Intermediate Similarity	NPD4109	Clinical (unspecified phase)
0.7086	Intermediate Similarity	NPD4110	Phase 3
0.7086	Intermediate Similarity	NPD3892	Phase 2
0.7081	Intermediate Similarity	NPD5494	Approved
0.7078	Intermediate Similarity	NPD5261	Clinical (unspecified phase)
0.7078	Intermediate Similarity	NPD7527	Clinical (unspecified phase)
0.7078	Intermediate Similarity	NPD7526	Approved
0.7078	Intermediate Similarity	NPD52	Approved
0.7075	Intermediate Similarity	NPD2568	Approved
0.7067	Intermediate Similarity	NPD1549	Phase 2
0.7066	Intermediate Similarity	NPD6559	Discontinued
0.7063	Intermediate Similarity	NPD4055	Discovery
0.7059	Intermediate Similarity	NPD6799	Approved
0.7059	Intermediate Similarity	NPD1774	Approved
0.7055	Intermediate Similarity	NPD1240	Approved
0.7047	Intermediate Similarity	NPD6100	Approved
0.7047	Intermediate Similarity	NPD6099	Approved
0.7045	Intermediate Similarity	NPD4750	Phase 3
0.7044	Intermediate Similarity	NPD8443	Clinical (unspecified phase)
0.7042	Intermediate Similarity	NPD3094	Phase 2
0.7041	Intermediate Similarity	NPD7090	Clinical (unspecified phase)
0.7041	Intermediate Similarity	NPD8053	Approved
0.7041	Intermediate Similarity	NPD8054	Approved
0.704	Intermediate Similarity	NPD2859	Approved
0.704	Intermediate Similarity	NPD2860	Approved
0.7034	Intermediate Similarity	NPD6798	Discontinued
0.7034	Intermediate Similarity	NPD5718	Phase 2
0.7034	Intermediate Similarity	NPD5109	Approved
0.7034	Intermediate Similarity	NPD5110	Phase 2

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